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7 Non-muscle invasive (TA, T1, CIS) Bladder Cancer

GUIDELINES ON NON-MUSCLE
INVASIVE
(
TA, T1, CIS
)
BLADDER
CANCER
(Text update March 2013)
M. Babjuk, M. Burger, R. Zigeuner, S. Shariat, B.W.G. van Rhijn,
E. Comprat, R. Sylvester, E. Kaasinen, A. Bhle, J. Palou,
M. Rouprt
Eur Urol 2011 Apr;59(4):584-94
Introduction
The EAU Working Group on Non-muscle-invasive Bladder
Cancer has published a short and long version of guidelines
on non-muscle-invasive bladder cancer which contains infor-
mation on its background, classification, risk factors, diagno-
sis, prognostic factors, and treatment.
The current recommendations for non-muscle-invasive
bladder cancer are ultra-short and are based on the current
literature (until the end of 2012), with emphasis being placed
on (evidence based) results from randomised clinical trials
and meta-analyses. These guidelines can be used as a quick
reference on the management of patients with non-muscle-
invasive bladder cancer.
The recommendations of this working panel apply to patients
with papillary stage Ta and T1 tumours as well as to car-
cinoma in situ (CIS), a flat neoplasm. The classification of
non-muscle-invasive tumours (Ta, T1, and CIS) is given in the
TNM Classification of Malignant Tumours, 7th Edition, 2009
(Table 1).
8 Non-muscle invasive (TA, T1, CIS) Bladder Cancer
Table 1: TNM Classification 2009
Urinary Bladder
T - Primary Tumour
Ta Non-invasive papillary carcinoma
CIS (Tis) Carcinoma in situ: flat tumour
T1 Tumour invades subepithelial connective tissue
T2 Tumour invades muscularis
T2a Superficial muscle (inner half)
T2b Deep muscle (outer half)
T3 Tumour invades perivesical tissue (beyond
muscularis)
T3a Microscopically
T3b Macroscopically (extravesical mass)
T4 Tumour invades any of the following: prostate,
uterus, vagina, pelvic wall, abdominal wall
T4a Prostate, uterus, or vagina
T4b Pelvic wall or abdominal wall
N - Lymph Nodes
NX Regional lymph nodes cannot be assessed
N0 No regional lymph node metatstasis
N1 Metastasis in a single lymph node in the true pelvis
(hypogastric, obturator, external iliac, or presacral)
N2 Mestastasis in multiple lymph nodes in the true
pelvis (hypogastric, obturator, external iliac, or pre-
sacral)
N3 Metastasis in a common iliac lymph node(s)
M - Distant Metastasis
MX Metastasis not assessed
M0 No distant metastasis
M1 Distant metastasis
9 Non-muscle invasive (TA, T1, CIS) Bladder Cancer
Characteristics of Stages Ta, T1, and CIS
Stage Ta tumours are confined to the urothelium, have a
papillary configuration of their exophytic part, and do not pen-
etrate from the urothelium into the lamina propria or detrusor
muscle.
Stage T1 tumours originate from the urothelium but penetrate
the basement membrane which separates the urothelium
from the deeper layers. T1 tumours invade into the lamina pro-
pria, but not into the detrusor muscle.
Carcinoma in situ (CIS) is a high-grade (anaplastic) carcinoma
confined to the urothelium, but with a flat non-papillary
configuration. CIS appears as reddened and velvety mucosa,
but is sometimes not visible. CIS can be local or diffuse. Four
types of CIS are distinguishable:
primary CIS (no previous or concurrent papillary tumours,
no previous CIS);
secondary CIS (with a history of papillary tumours, but not
CIS);
concurrent CIS (in the presence of papillary tumours in the
bladder);
recurrent CIS (repeat occurrence of isolated CIS).
Characteristics of Grade
1973 WHO Classification
Apart from their architecture, the individual cells show differ-
ent degrees of anaplasia:
Grade 1: well differentiated tumour
Grade 2: moderately differentiated tumour
Grade 3: poorly differentiated tumour
2004 WHO Classification
A new classification system was initially proposed by the
WHO/ISUP in 1998 and updated by the WHO in 2004. For non-
10 Non-muscle invasive (TA, T1, CIS) Bladder Cancer
invasive urothelial neoplasias, the categories described in
Table 2 are used.
Table 2: 2004 WHO Classification of non-invasive urothelial
neoplasia
Flat lesions
Hyperplasia (flat lesion without atypia or papillary)
Reactive atypia (flat lesion with atypia)
Atypia of unknown significance
Urothelial dysplasia
Urothelial carcinoma in situ (CIS)
Papillary lesions
Urothelial papilloma (a completely benign lesion)
Papillary urothelial neoplasm of low malignant potential
(PUNLMP)
Low-grade papillary urothelial carcinoma
High-grade papillary urothelial carcinoma
The 2004 WHO grading system defines CIS as a non-papillary,
i.e. a flat, lesion in which the surface epithelium contains cells
that are cytologically malignant. Papillary tumours are classi-
fied as either papillary urothelial neoplasms of low malignant
potential (PUNLMP) or as urothelial carcinomas, with the
latter being subdivided into two grades: low grade and high
grade (Table 2).
The intermediate group (G2) has been eliminated; this group
was the subject of controversy in the 1973 WHO classifica-
tion. Use of the 2004 WHO classification is advocated, as this
should result in less diagnostic variability among pathologists.
However until the 2004 WHO classification has been validated
clinically, both classifications should be used.
The majority of clinical trials published so far on Ta, T1 bladder
tumours have been performed using the 1973 WHO classifica-
11 Non-muscle invasive (TA, T1, CIS) Bladder Cancer
tion, and therefore the following guidelines are based on the
1973 WHO grade classification.
Diagnosis and Initial Treatment Steps
The diagnosis mainly depends on the cystoscopic examina-
tion of the bladder, biopsy, and urine cytology. To date, molec-
ular urinary markers have not improved the combination of
cystoscopy and cytology.
The standard initial therapy for Ta and T1 papillary bladder
tumours is complete macroscopic transurethral resection
(TURB), including a part of the underlying muscle. TURB
should be performed systematically in individual steps, which
are described in the full version of the guidelines. Small
tumours (< 1 cm) can be resected en bloc including a part of
the underlying muscle. Larger tumours should be resected
separately in fractions, which include the exophytic part of
the tumour, the underlying bladder wall with the detrusor
muscle and the edges of the resection area. The specimens
from different fractions must be referred to the pathologist in
separate containers.
A second TURB 2-6 weeks after initial resection is recom-
mended in the following situations: after incomplete initial
TURB, if there was no muscle in the specimen after initial
resection (with exception of Ta low grade (G1) tumours), in all
T1 tumours and in all high grade (G3) tumours (except primary
CIS).
The diagnosis of CIS is based on the histology of biopsies from
the bladder wall. Biopsies are taken from suspect areas.
In patients with positive urine cytology and no papillary
tumour, multiple biopsies from normal looking mucosa includ-
ing prostatic urethra (random biopsies) are recommended.
Fluorescence cystoscopy is recommended in these cases as it
12 Non-muscle invasive (TA, T1, CIS) Bladder Cancer
improves the detection rate of CIS. Urine cytology is an impor-
tant tool in the diagnosis and follow-up of CIS because of its
high sensitivity and specificity (over 90%).
CIS cannot be eradicated by TUR and further treatment is
mandatory.
Prognostic Factors and Adjuvant Treatment
TaT1 papillary tumours
It is recommended to stratify patients according to prognos-
tic factors into three risk groups that will facilitate treatment
recommendations. Their definition, which takes into account
the EORTC risk tables probabilities of recurrence and espe-
cially progression, can be found in Table 3. For individual
prediction of the risk of tumour recurrence and progression
at different intervals after TURB, application of EORTC risk
tables and calculator (http://www.eortc.be/tools/bladdercal-
culator/) is strongly recommended.
Table 3: Treatment recommendations in TaT1 tumours
according to risk stratification
Risk category Definition Treatment recom-
mendation
Low-risk
tumours
Primary, solitary,
Ta, G1, < 3 cm, no
CIS
One immediate
instillation of
chemotherapy
Intermediate-risk
tumours
All cases between
categories of low
and high risk
One immediate
instillation of
chemotherapy fol-
lowed by further
instillations, either
chemotherapy for a
maximum of 1 year
or 1 year full-dose
BCG
13 Non-muscle invasive (TA, T1, CIS) Bladder Cancer
High-risk
tumours
Any of the follow-
ing:
T1 tumours
G3 tumours
CIS
Multiple and
recurrent and
large (> 3 cm) Ta
G1G2 tumours (all
these conditions
must be pre-
sented)
Intravesical full-
dose BCG instilla-
tions for 1-3 years
or radical cystec-
tomy (in highest
risk tumours)
Subgroup of
highest-risk
tumours
T1G3 associated
with concurrent
bladder CIS,
multiple and/or
large T1G3 and/
or recurrent T1G3,
T1G3 with CIS in
prostatic urethra,
micropapillary
variant of urothelial
carcinoma
Radical cystectomy
should be consid-
ered
BCG refractory
tumours
Radical cystectomy
is recommended
Since there is considerable risk for recurrence and/or progres-
sion of tumours after TURB, adjuvant intravesical therapy is
recommended for all stages (Ta, T1, and CIS). Immediate post-
operative instillation of chemotherapy within 6 hours after
TURB is recommended in tumours presumed to be at low or
intermediate risk, except in cases of bladder perforation or
severe bleeding. The choice of drug (mitomycin C, epirubicin,
or doxorubicine) is optional. The choice of further intravesical
adjuvant therapy depends on the patients risk.
14 Non-muscle invasive (TA, T1, CIS) Bladder Cancer
Intravesical chemotherapy reduces the risk of recurrence but
not progression and is associated with minor side-effects.
Intravesical immunotherapy with Bacillus Calmette-Gurin
(BCG) (induction and maintenance) is superior to intravesi-
cal chemotherapy in reducing recurrences and in preventing
or delaying progression to muscle-invasive bladder cancer.
However, intravesical BCG is more toxic.
Recommendations for Low Risk Tumours GR
Patients with a single, small, low grade Ta tumour
without CIS are at low risk, they should receive:
1. A complete TURB. A
2. An immediate single post-operative instillation with
a chemotherapeutic agent (drug optional).
A
3. No further treatment is recommended prior to
disease recurrence.
A
Recommendations for Intermediate Risk Tumours GR
The major issue in the management of intermediate
risk tumours is to prevent recurrence and progression,
of which disease recurrence is clinically the most fre-
quent. Treatment should include:
1. Complete TURB followed by an immediate postop-
erative instillation with a chemotherapeutic agent
(drug optional).
A
2. A second TURB after 4-6 weeks when indicated. B
3a Adjuvant intravesical immunotherapy with BCG, 1
year full dose;
A
Or
3b Adjuvant intravesical chemotherapy (drug option-
al), schedule: optional although the duration of
treatment should not exceed 1 year.
A
15 Non-muscle invasive (TA, T1, CIS) Bladder Cancer
Recommendations for High Risk Tumours GR
The treatment of Ta, T1 tumours at high risk should
consist of:
1. Complete TURB of papillary tumours. C
2. A second TURB after 4-6 weeks. B
3. Adjuvant intravesical immunotherapy with BCG (full
dose).
Maintenance therapy for 1-3 years is necessary
although the optimal maintenance scheme has not
yet been determined.
A
4. Immediate radical cystectomy may be offered to
patients at highest risk of tumour progression.
C
5. In patients with BCG failure, radical cystectomy is
recommended.
B
Carcinoma in situ
CIS has a high risk of progression to muscle-invasive disease
which exceeds 50% in some studies.
BCG intravesical immunotherapy (induction and mainte-
nance) is superior to intravesical chemotherapy in increasing
the complete response rate and the overall percentage of
patients remaining tumour free. Moreover, BCG reduces the
risk of progression as compared to either intravesical chemo-
therapy or a different immunotherapy. Early radical cystec-
tomy at the time of diagnosis provides excellent disease-free
survival, but over-treatment occurs in up to 50% of patients.
16 Non-muscle invasive (TA, T1, CIS) Bladder Cancer
Recommendations for the treatment of CIS GR
1. In concurrent CIS, the initial strategy (TURB, early
intravesical instillation, a second TURB) is based on
the features of the papillary tumour.
2. Intravesical BCG immunotherapy, full dose with 1-3
years of maintenance.
A
3. After the 6 week induction course, a second course
of 6 weekly BCG instillations or maintenance cycles
consisting of 3 weekly instillations may be consid-
ered in non responders since about 40-60% of these
patients will respond to additional treatment with
BCG.
B
4. In BCG non-responders at 6 months radical cystec-
tomy is recommended.
B
Follow-up for non-muscle invasive bladder tumours
Patients with non-muscle-invasive bladder tumours need to
be regularly followed up because of the risk of disease recur-
rence and progression; however, the frequency and duration
of cystoscopies should reflect the degree of risk.
When planning a follow-up schedule, the following aspects
should be considered:
a. The prompt detection of muscle-invasive and high-grade
non-muscle-invasive recurrences is critical since a delay in
diagnosis and therapy threatens a patients life.
b. Tumour recurrence in the low-risk group is nearly always
low stage and low grade. Small, non-invasive (Ta), low
grade papillary recurrences do not present an immedi-
ate danger to the patient and their early detection is not
essential for successful therapy. In these patients, fulgura-
tion of small papillary recurrences on an outpatient basis is
considered to be a safe treatment option.
c. The result of the first cystoscopy after TURB at 3 months is
17 Non-muscle invasive (TA, T1, CIS) Bladder Cancer
a very important prognostic factor for disease recurrence
and for progression. The first cystoscopy should thus
always be performed 3 months after TURB.
d. The risk of upper urinary tract recurrence increases in
patients with multiple and high risk tumours.
The following recommendations are only based on retrospec-
tive experience.
Recommendations for follow-up GR
The follow-up of Ta T1 tumours is based on regular
cystoscopy.
A
Patients with low-risk Ta tumours should undergo
cystoscopy at 3 months. If negative, subsequent cys-
toscopy is advised 9 months later, and then yearly for
5 years.
C
Patients with high-risk tumours should undergo
cystoscopy and urinary cytology at 3 months. If nega-
tive, subsequent cystoscopy and cytology should be
repeated every 3 months for a period of 2 years, and
every 6 months thereafter until 5 years, and then
yearly.
C
Patients with intermediate-risk Ta T1 tumours should
have an in-between follow-up scheme using cystos-
copy and cytology, which is adapted according to
personal and subjective factors.
C
Regular (yearly) upper tract imaging (CT-IVU or IVU) is
recommended for high-risk tumours.
C
Endoscopy under anaesthesia and bladder biopsies
should be performed when office cystoscopy shows
suspicious findings or if urinary cytology is positive.
B
18 Non-muscle invasive (TA, T1, CIS) Bladder Cancer
During follow-up in patients with positive cytology
and no visible tumour in the bladder, R-biopsies or
biopsies with PDD (if equipment is available) and
investigation of extravesical locations (CT urography,
prostatic urethra biopsy) are recommended.
B
This short booklet text is based on the more comprehensive EAU
guidelines (ISBN 978-90-79754-71-7), available to all members of the
European Association of Urology at their website,
http://www.uroweb.org.
19 Urothelial Carcinomas Of The Upper Urinary Tract
GUIDELINES ON UROTHELIAL
CARCINOMAS OF THE UPPER
URINARY TRACT
(
UTUCs
)
(Text update March 2013)
M. Rouprt, M. Babjuk, E. Comprat, R. Zigeuner, R. Sylvester,
M. Burger, A. Bhle, B.W.G. Van Rhijn, E. Kaasinen, J. Palou,
S.F. Shariat
Eur Urol 2011 Apr;59(4):584-94
Introduction
UTUCs are uncommon and account for only 5-10% of urotheli-
al cell carcinomas. They have a similar morphology to bladder
carcinomas and nearly all UTUCs are urothelial in origin.
Classification
Table 1: TNM classification 2009 for renal pelvis and ureter
T - Primary tumour
TX
T0
Ta
Tis
T1
T2
T3
T4
Primary tumour cannot be assessed
No evidence of primary tumour
Non-invasive papillary carcinoma
Carcinoma in situ
Tumour invades subepithelial connective tissue
Tumour invades muscularis
Renal pelvis: tumour invades beyond muscularis into
peripelvic fat or renal parenchyma
Ureter: tumour invades beyond muscularis into
periureteric fat
Tumour invades adjacent organs or through the
kidney into perinephric fat
20 Urothelial Carcinomas Of The Upper Urinary Tract
N - Regional lymph nodes
NX
N0
N1
N2
N3
Regional lymph nodes cannot be assessed
No regional lymph node metastasis
Metastasis in a single lymph node 2 cm or less in the
greatest dimension
Metastasis in a single lymph node more than 2 cm
but not more than 5 cm in the greatest dimension,
or multiple lymph nodes, none more than 5 cm in
greatest dimension
Metastasis in a lymph node more than 5 cm in
greatest dimension
M - Distant metastasis
M0
M1
No distant metastasis
Distant metastasis
Tumour grade
There are currently two main classifications used for UTUCs.
They are the 1973 WHO classification, which classifies
tumours into three grades, G1, G2 and G3, and the 2004 WHO
classification, which classifies tumours into three groups:
papillary urothelial neoplasia of low malignant potential, low-
grade carcinomas, and high-grade carcinomas. Upper urinary
tract tumours with low malignant potential are very rare.
Diagnosis
UTUCs are diagnosed using imaging, cystoscopy, urinary
cytology and diagnostic ureteroscopy. The benefits of ureter-
oscopy in pre-operative assessment should also be discussed
with the patient.
Recommendations for diagnosis of UTUCs GR
Urinary cytology A
Cystoscopy to rule out a concomitant bladder tumour A
CT urography A
21 Urothelial Carcinomas Of The Upper Urinary Tract
Diagnostic ureteroscopy and biopsy C
Retrograde ureteropyelography C
Prognostic factors
UTUCs that invade the muscle wall usually have a very poor
prognosis. Recognised prognostic factors in decreasing order
of importance include: tumour stage and grade; concomitant
carcinoma in situ (CIS); age; lymphovascular invasion; tumour
architecture; extensive tumour necrosis; molecular markers;
tumour location; and gender.
Management
Localised disease in UTUCs
Radical management (radical nephroureterectomy, RNU)
The radical management of UTUCs consists of open surgery
RNU with excision of the bladder cuff. This is the gold stand-
ard treatment for UTUCs, regardless of tumour location. It
includes resection of the distal ureter and its orifice because
of the high risk of recurrence in this area. Lymph node dis-
section is also carried out as part of treatment and to provide
optimal staging.
Recommendations for radical management (i.e. radical
nephroureterectomy)
Indications GR
Suspicion of infiltrating UTUC on imaging B
High-grade tumour (urinary cytology) B
Multifocality (with two functional kidneys) B
Non-invasive but large (i.e. > 2 cm) UTUC B
Choice of technique
Open and laparoscopic access are equally effective B
Bladder cuff removal is imperative A
22 Urothelial Carcinomas Of The Upper Urinary Tract
Several techniques for bladder cuff excision are
acceptable, except stripping
C
Lymphadenectomy is recommended in the case of
invasive UTUC
C
Postoperative instillation (chemotherapy) is
recommended after RNU to avoid bladder recurrence
B
Conservative management (low-risk UTUCs)
Conservative management of low-risk UTUCs consists of
surgery preserving the upper urinary renal unit. It is used
in imperative cases (renal insufficiency, solitary functional
kidney) or in selected elective cases (functional contralat-
eral kidney) for low-grade, low-stage tumours. The choice of
technique (ureteroscopy, segmental resection, percutaneous
access) depends on technical constraints, the anatomical
location of the tumour, and the experience of the surgeon.
Recommendations for conservative management (low-risk
UTUCs)
Indications GR
Unifocal tumour B
Small tumour (size < 1 cm) B
Low-grade tumour (cytology or biopsies) B
No evidence of an infiltrative lesion on CT urography B
Understanding of close follow-up B
Techniques
Laser should be used in the case of endoscopic
treatment
C
Flexible ureteroscopy is preferable to rigid
ureteroscopy
C
A percutaneous approach is an option for small, low-
grade, caliceal tumours unsuitable for ureteroscopic
treatment
C
23 Urothelial Carcinomas Of The Upper Urinary Tract
Ureteroureterostomy is an option for non-invasive,
low-grade tumours of the proximal ureter or mid-ureter
that cannot be removed completely by endoscopic
means
C
Complete distal ureterectomy and neocystostomy is
an option for non-invasive, low-grade tumours in the
distal ureter that cannot be removed completely by
endoscopic means
C
The instillation of Bacillus Calmette-Gurin (BCG) or mitomy-
cin C in the urinary tract by percutaneous nephrostomy or
via a ureteric stent is technically feasible after conservative
treatment of UTUCs. However, the benefits have not been
confirmed.
Advanced disease in UTUCs
RNU has no benefit in metastatic (M+) disease, but may be
used in palliative care. As UTUCs are urothelial tumours, plati-
num-based chemotherapy should give similar results to those
in bladder cancer. Currently, insufficient data are available to
provide any recommendations.
Radiotherapy is scarcely relevant nowadays both as a unique
therapy and associated with chemotherapy as a tumour adju-
vant.
Follow-up after initial treatment
In all cases, there should be strict follow-up after radical man-
agement to detect metachronous bladder tumours, as well as
invasive tumours, local recurrence and distant metastases. In
conservative management, the ipsilateral upper urinary tract
requires careful follow-up due to the high risk of recurrence.
24 Urothelial Carcinomas Of The Upper Urinary Tract
Recommendation
After radical management, over at least 5 years GR
Non-invasive tumour
Cystoscopy/urinary cytology at 3 months and then
annually
C
CT every year C
Invasive tumour
Cystoscopy/urinary cytology at 3 months and then
annually
C
CT urography every 6 months for 2 years and then
annually
C
After conservative management, over at least 5 years
Urinary cytology and CT urography at 3 months,
6 months and then annually
C
Cystoscopy, ureteroscopy and cytology in situ at
3 months, 6 months, every 6 months for 2 years and
then annually
C
25 Urothelial Carcinomas Of The Upper Urinary Tract
Figure 1: Proposed flowchart for the management of UTUC
This short booklet text is based on the more comprehensive EAU
guidelines (ISBN: 978-90-79754-71-7), available to all members of the
European Association of Urology at their website,
http://www.uroweb.org.
Diagnostics evaluation: CT-urography,
urinary cytology, cystoscopy
retrograde pyelography
- Unifocal tumour
- Size < 1 cm
- Low-grade tumour
- Superfcial aspect on
CT-urography
Gold standard treatment:
Radical nephroureterectomy
+/- fexible ureteroscopy with
biopsies
Conservative management:
ureteroscopy, segmental resection
Open
Recurrence
Close and stringent follow-up
Laparoscopic
UTUC
Muscle-invasive and Metastatic Bladder Cancer 26
MUSCLE-INVASIVE AND METASTATIC
BLADDER CANCER
(Text update March 2013)
J.A. Witjes (chair), E. Comprat, N.C. Cowan, G. Gakis,
M. De Santis, T. Lebret, M.J. Ribal, A. Sherif
Eur Urol 2011 Jun;59(6):1009-18
Introduction
Optimal treatment strategies for MIBC require the involve-
ment of a specialist multidisciplinary team and a model of
integrated care to avoid fragmentation of patient care.
Staging system
The UICC 2009 TNM (Tumour, Node, Metastasis
Classification) is used for staging.
27 Muscle-invasive and Metastatic Bladder Cancer
Table 1: 2009 TNM classification of urinary bladder cancer
T - Primary tumour
TX
T0
Ta
Tis
T1
T2
T3
Primary tumour cannot be assessed
No evidence of primary tumour
Non-invasive papillary carcinoma
Carcinoma in situ: flat tumour
Tumour invades subepithelial connective tissue
Tumour invades muscle
T2a Tumour invades superficial muscle
(inner half)
T2b Tumour invades deep muscle
(outer half)
Tumour invades perivesical tissue
T3a Microscopically
T3b Microscopically (extravesical mass)
T4 Tumour invades any of the following: prostate,
uterus, vagina, pelvic wall, abdominal wall
T4a Tumour invades prostate, uterus or vagina
T4b Tumour invades pelvic wall or
abdominal wall
N - Lymph nodes
NX
N0
N1
N2
N3
Regional lymph nodes cannot be assessed
No regional lymph node metastasis
Metastasis in a single lymph node in the true pelvis
(hypogastric, obturator, external iliac or presacral)
Metastasis in multiple lymph nodes in the true pelvis
(hypogastric, obturator, external iliac or presacral)
Metastasis in a common iliac lymph node(s)
M - Distant metastasis
M0
M1
No distant metastasis
Distant metastasis

Muscle-invasive and Metastatic Bladder Cancer 28
Table 2: WHO grading 1973 and 2004
(Both classifications are used for the current guidelines
since most of the retrospective studies were based on the
old WHO 1973 grading system).
1973 WHO grading
Urothelial papilloma
Grade 1: well differentiated
Grade 2: moderately differentiated
Grade 3: poorly differentiated
2004 WHO grading
Urothelial papilloma
Papillary urothelial neoplasm of low malignant potential
(PUNLMP)
Low-grade papillary urothelial carcinoma
High-grade papillary urothelial carcinoma
Morphological subtypes can be important for helping with
prognosis and treatment decisions. Currently the following
differentiation is used:
1. Urothelial carcinoma (more than 90% of all cases)
2. Urothelial carcinomas with squamous and/or glandular
partial differentiation
3. Micropapillary urothelial carcinoma
4. Nested carcinoma
5. Some urothelial carcinomas with trophoblastic
differentiation
6. Small cell carcinomas
7. Spindle cell carcinomas.
Recommendations for assessing tumour specimens
Mandatory evaluations
Histological subtype
Depth of invasion
Resection margins, including CIS
29 Muscle-invasive and Metastatic Bladder Cancer
Extensive lymph-node representation
Optional evaluation
Bladder wall blood vessel invasion
CIS, carcinoma in situ.
Specific recommendations for primary assessment of pre-
sumably invasive bladder tumours
(General information for assessment of bladder tumours, see
EAU Guidelines on Non-muscle-invasive Bladder cancer)
Recommendations GR
Cystoscopy should describe all macroscopic features
of the tumour (site, size, number and appearance) and
mucosal abnormalities. A bladder diagram is
recommended.
C
Biopsy of the prostatic urethra is recommended for
cases of bladder neck tumour, when bladder CIS is
present or suspected, when there is positive cytology
without evidence of tumour in the bladder, or when
abnormalities of the prostatic urethra are visible.
If biopsy is not performed during the initial procedure,
it should be completed at the time of the second
resection.
C
In women undergoing a subsequent orthotopic neob-
ladder, procedure information is required (including a
histological evaluation) of the bladder neck and ure-
thral margin, either prior to, or at the time of
cystoscopy.
C
The pathological report should specify the grade, the
depth of tumour invasion and whether the lamina pro-
pria and muscle tissue are present in the specimen.
C
Muscle-invasive and Metastatic Bladder Cancer 30
Recommendations for staging of MIBC GR
In patients with confirmed muscle-invasive bladder
cancer, CT of the chest, abdomen and pelvis is the
optimal form of staging, including excretory-phase
CT urography for complete examination of the upper
urinary tracts.
B
Excretory-phase CT urography is preferred to MR
urography for diagnosing UTUCs in terms of greater
diagnostic accuracy, less cost, and greater patient
acceptability. MR urography is used when CT urogra-
phy is contra-indicated for reasons related to contrast
administration or radiation dose.
C
Ureteroscopic-guided biopsy is recommended for
histopathological confirmation of diagnosis in the
preoperative assessment of UTUC.
C
CT or MRI is recommended for staging locally
advanced or metastatic disease in patients in whom
radical treatment is being considered.
C
CT and MRI are generally equivalent in diagnosing
local and distant abdominal metastases but CT is
preferred to diagnose pulmonary metastases.
C
Treatment failure of non-muscle invasive bladder
tumours
Recommendations for treatment failure of non-mus-
cle-invasive bladder cancer
GR
In all T1 tumours at high risk of progression (i.e. high
grade, multifocality, carcinoma in situ, and tumour
size, as outlined in the EAU guidelines for Non-muscle-
invasive bladder cancer), immediate radical treatment
is an option.
B
In all T1 patients failing intravesical therapy, radical
treatment should be offered.
B
31 Muscle-invasive and Metastatic Bladder Cancer
Muscle-invasive bladder cancer - Radical Surgery and
Urinary Diversion
Conclusions LE
For muscle-invasive bladder cancer radical cystec-
tomy is the curative treatment of choice.
3
A higher case load reduces morbidity and mortality of
cystectomy.
3
There is data to support that an extended LND (versus
a standard or limited LND) improves survival after
radical cystectomy.
3
Radical cystectomy in both sexes must not include
the removal of the entire urethra in all cases, which
may then serve as outlet for an orthotopic bladder
substitution.
3
Terminal ileum and colon are the intestinal segments
of choice for urinary diversion.
3
The type of urinary diversion does not affect oncologi-
cal outcome.
3
Laparoscopic and robotic-assisted laparoscopic cys-
tectomy is feasible but still investigational.
3
In patients with invasive bladder cancer older than 80
years cystectomy is an option.
3
Surgical outcome is influenced by comorbidity, age,
previous treatment for bladder cancer or other pelvic
diseases, surgeon and hospital volumes of cystec-
tomy, and type of urinary diversion.
2
Surgical complications of cystectomy and urinary
diversion should be reported in a uniform grading sys-
tem. Currently, the best-adapted, graded system for
cystectomy is the Clavien grading system.
2
Contraindications for orthotopic bladder substitution are
Muscle-invasive and Metastatic Bladder Cancer 32
positive margins at the level of urethral dissection, positive
margins anywhere on the bladder specimen (in both sexes),
if the primary tumour is located at the bladder neck or in the
urethra (in women), or if tumour extensively infiltrates the
prostate (in men).
Recommendations for radical cystectomy GR
Radical cystectomy is recommended in T2-T4a, N0
M0, and high risk non-muscle-invasive BC.
A*
Do not delay cystectomy more than 3 months since it
increases the risk of progression and cancer-specific
death.
B
Pre-operative radiotherapy is not recommended in
case of subsequent cystectomy with urinary diversion.
A
Lymph node dissection should be an integral part of
cystectomy. An extended LND is recommended.
B
The urethra can be preserved if margins are negative.
If no bladder substitution is attached, the urethra
must be checked regularly.
B
Laparoscopic and robot-assisted laparoscopic cystec-
tomy are both options. However, current data have
not sufficiently proven the advantages or disadvan-
tages for both oncological and functional outcomes
of laparoscopic and robotic-assisted laparoscopic
cystectomy.
C
Before cystectomy, the patient should be fully
informed about the benefits and potential risks of all
possible alternatives, and the final decision should be
based on a balanced discussion between patient and
surgeon.
B
33 Muscle-invasive and Metastatic Bladder Cancer
The decision regarding bladder sparing or radical cys-
tectomy in the elderly/geriatric patient with invasive
bladder cancer should be based on tumour stage and
comorbidity best quantified by a validated score, such
as the Charlson score.
B
Pre-operative bowel preparation is not mandatory,
fast track measurements may reduce the time of
bowel recovery.
C
An orthotopic bladder substitute should be offered to
male and female patients lacking any contraindica-
tions and who have no tumour in the urethra and at
the level of urethral dissection.
B
*Upgraded following panel consensus
Neoadjuvant chemotherapy
Neoadjuvant cisplatin-containing combination chemotherapy
improves overall survival, irrespective of the type of defini-
tive treatment (LE: 1a). It has its limitations regarding patient
selection, current development of surgical technique, and
current chemotherapy combinations. In current routine clini-
cal practice, it is difficult to select patients who will respond
to neoadjuvant chemotherapy due to the lack of an appli-
cable test. In the future, genetic markers, in a personalized
medicine setting, are expected to make it easier to select
patients for treatment and to differentiate responders from
non-responders.
Recommendations GR
Neoadjuvant chemotherapy is recommended for
T2-T4a, cN0M0 bladder cancer and should always be
cisplatinum-based combination therapy.
A
Neoadjuvant chemotherapy is not recommended in
patients with PS 2 and/or impaired renal function.
B
In case of progression under neoadjuvant chemo-
therapy, this treatment should be discontinued.
Muscle-invasive and Metastatic Bladder Cancer 34
Bladder-sparing treatments for localised disease
Transurethral resection of bladder tumour (TURB)
TURB alone is only possible as a therapeutic option if tumour
growth is limited to the superficial muscle layer and if re-stag-
ing biopsies are negative for residual tumour.
External beam radiotherapy
External beam radiotherapy alone should only be consid-
Diagnosis
Cystoscopy and tumour resection
Evaluation of urethra
CT imaging of abdomen, chest, UUT
MR can be used for local staging
1 - males: biopsy apical prostatic
urethra or frozen section during
surgery
1 - females: biopsy of proximal urethra
or frozen section during surgery
pT2N0M0 selected patients
- Multimodality bladder sparing
therapy can be considered for T2
tumours
(Note: alternative, not the standard
option)
2 - neoadjuvant radiotherapy is not
recommended
Findings:
pT2-3, clinical N0M0 urothelial
carcinoma of the bladder
Neoadjuvant chemotherapy
Should be considered in selected
patients
5-7% 5 year survival benefit
Radical cystectomy
Know general aspects of surgery
o Preparation
o Surgical technique
o Integrated node dissection
o Urinary diversion
o Timing of surgery
A higher case load improves outcome
Direct adjuvant chemotherapy
Not indicated after cystectomy
Fig. 1: Flowchart for the management for T2-T4a N0M0 urothe-
lial bladder cancer
35 Muscle-invasive and Metastatic Bladder Cancer
ered as a therapeutic option when the patient is unfit for
cystectomy or a multimodality bladder-preserving approach.
Radiotherapy can also be used to stop bleeding from the
tumour when local control cannot be achieved by transure-
thral manipulation because of extensive local tumour growth
(LE: 3).
Surgically non-curable tumours
Palliative cystectomy for metastatic disease
Primary radical cystectomy in T4b bladder cancer is not a
curative option. If there are symptoms, radical cystectomy
may be a therapeutic/palliative option. Intestinal or non-intes-
tinal forms of urinary diversion can be used, with or without,
palliative cystectomy.
Recommendations LE GR
In patients with inoperable locally advanced
tumours (T4b), primary radical cystectomy is a
palliative option and cannot be offered as
curative treatment.
B
In patients with symptoms palliative cystec-
tomy may be offered.
Prior to any further interventions, surgery-
related morbidity and quality-of-life should be
fully discussed with the patient.
3 B
Chemotherapy and best supportive care
With cisplatin-based chemotherapy as primary therapy for
locally advanced tumours in highly selected patients, com-
plete and partial local responses have been reported. (LE: 2b).
Recommendation GR
Chemotherapy alone is not recommended as primary
therapy for localised bladder cancer.
A
Muscle-invasive and Metastatic Bladder Cancer 36
Adjuvant Chemotherapy
Neither randomized trials nor a meta-analysis have provided
sufficient data to support the routine use of adjuvant
chemotherapy (LE: 1a).
Recommendation GR
Adjuvant chemotherapy is advised within clinical
trials, but not as a routine therapeutic option.
A
Multimodality treatment
Conclusions LE
In a highly selected patient population, long-term sur-
vival rates of multimodality treatment are comparable
to those of early cystectomy.
3
Delay in surgical therapy can compromise survival
rates.
2b
Recommendations GR
Transurethral resection of bladder tumour (TURB)
alone cannot be offered as a standard curative treat-
ment option in most patients.
B
Radiotherapy alone is less effective than surgery and
is only recommended as a therapeutic option when
the patient is unfit for cystectomy or a multimodality
bladder-preserving approach.
B
Chemotherapy alone is not recommended as primary
therapy for muscle-invasive bladder cancer.
A
Surgical intervention or multimodality treatment are
the preferred curative therapeutic approaches since
they are more effective than radiotherapy alone.
B
37 Muscle-invasive and Metastatic Bladder Cancer
Multimodality treatment could be offered as an alter-
native in selected, well-informed, well selected and
compliant patients, especially for whom cystectomy is
not an option.
B
Metastatic disease
Conclusions for metastatic disease LE
In a first-line setting, PS and the presence or absence
of visceral metastases are independent prognostic
factors for survival.
1b
In a second-line setting, prognostic factors are: liver
metastasis, PS and haemoglobin (< 10 g/dL)
2
Cisplatin-containing combination chemotherapy can
achieve median survival of up to 14 months, with long-
term disease-free survival reported in ~15% of patients
with nodal disease and good PS.
1b
Carboplatin combination chemotherapy is less
effective than cisplatin-based chemotherapy in terms
of complete response and survival.
2a
There is no defined standard chemotherapy for unfit
patients with advanced or metastatic urothelial
cancer.
2b
Vinflunine reached the highest level of evidence ever
reported for second-line use.
1b
Post-chemotherapy surgery after partial or complete
response may contribute to long-term disease-free
survival.
3
Zoledronic acid and denosumab have been approved
for all cancer types including urothelial cancer,
because they reduce and delay SREs in metastatic
bone disease.
1
Muscle-invasive and Metastatic Bladder Cancer 38
Recommendations for metastatic disease GR
First-line treatment for fit patients:
Use cisplatin-containing combination chemotherapy
with GC, PCG, MVAC, preferably with G-CSF, or
HD-MVAC with G-CSF.
A
Carboplatin and non-platinum combination chemo-
therapy is not recommended.
B
First-line treatment in patients ineligible (unfit) for cisplatin:
For cisplatin-ineligible (unfit) patients, with PS2 or
impaired renal function, as well as those with 0-1 poor
Bajorin prognostic factors and impaired renal func-
tion, treatment with carboplatin-containing combi-
nation chemotherapy, preferably with gemcitabine/
carboplatin is indicated.
A
Second-line treatment:
In patients progressing after platinum-based
combination chemotherapy for metastatic disease,
vinflunine should be offered. Alternatively, treatment
within a clinical trial setting may be offered.
B*
Zoledronic acid or denosumab is recommended for
treatment of bone metastases.
B
*Upgraded to Grade B recommendation; data not reaching
statistical significance.
Recommendation for the use of biomarkers GR
Currently, no biomarkers can be recommended in
daily clinical practice since they have no impact on
predicting outcome, treatment decisions or monitor-
ing therapy in muscle-invasive bladder cancer.
A*
*Upgraded following panel consensus.
39 Muscle-invasive and Metastatic Bladder Cancer
Fig. 2: Flowchart for the management of metastatic urothelial
cancer
Patient characteristics:
PS 0-1/ 2/ >2
GFR
>
/
<
60mL/min
Comorbidities
C I S P L A T I N ?
YES NO NO
Second-line treatment
PS 0 -1 and
GFR
>
60mL/min
STANDARD GC
MVAC
HD MVAC
PS 2 or
GFR < 60mL/min
comb. chemo: Carbo- based
PS 0-1 PS
>
2
PS
>
2 and
GFR < 60mL/min
NO comb.chemo
studies, monotherapy, BSC
1. Progression > 6 -12
months after first-line
chemotherapy, adequate
renal function
a. re-exposition to
first line treatment
(cisplatin based)
b. clinical study
2. Progression
> 6 -12 months
after first-line
chemotherapy,
PS 0-1, impaired
renal function
a. Vinflunine
b. clinical study
3. Progression
< 6 -12 months
after first-line
chemotherapy,
PS 0-1
a. Vinflunine
b. clinical study
a. best supportive care
b. clinical study
Muscle-invasive and Metastatic Bladder Cancer 40
Health-related quality-of-life (HRQoL)
Important determinants of (subjective) quality of life are a
patients personality, coping style and social support.
Recommendations for HRQoL GR
The use of validated questionnaires is recommended
to assess HRQoL in patients with muscle-invasive
bladder cancer.
B
Unless a patients co-morbidities, tumour variables
and coping abilities present clear contra-indications, a
continent urinary diversion should be offered.
C
Pre-operative patient information, patient selection,
surgical techniques, and careful post-operative follow-
up are the cornerstones for achieving good long-term
results.
C
Patient should be encouraged to take active part in
the decision-making process. Clear and exhaustive
information on all potential benefits and side-effects
should be provided, allowing them to make informed
decisions.
C
This short booklet text is based on the more comprehensive EAU
guidelines (ISBN 978-90-79754-71-7), available to all members of the
European Association of Urology at their website,
http://www.uroweb.orgg.
41 Prostate Cancer
GUIDELINES ON PROSTATE CANCER
(Text update February 2012)
A. Heidenreich (chairman), P.J. Bastian, J. Bellmunt, M. Bolla,
S. Joniau, T.H. van der Kwast, M.D. Mason, V. Matveev,
N. Mottet, T. Wiegel, F. Zattoni
Eur Urol 2008 Jan;53(1):68-80
Eur Urol 2011 Jan;59(1):61-71
Eur Urol 2011 Apr;59(4):572-83
Introduction
Cancer of the prostate (PCa) is currently the second most
common cause of cancer death in men. In developed coun-
tries PCa accounts for 15% of male cancers compared with
4% of male cancers in developing countries. Within Europe
exist also large regional differences in the incidence rates of
PCa.
There are three well-established risk factors for PCa: increas-
ing age, ethnic origin, and genetic predisposition. Clinical data
suggest that exogenous risk factors, such as diet, pattern of
sexual behaviour, alcohol consumption, exposure to ultra-
violet radiation, and occupational exposure may also play an
important role in the risk of developing PCa.
The introduction of an effective blood test, prostate-specific
antigen (PSA), has resulted in more early-stage prostate can-
cer diagnosis where potentially curative treatment options
can be provided. However, if effective diagnostic procedures
are inappropriately used in elderly men with a short life span,
the issue of over-diagnosis and over-treatment may occur.
Consequently, the same stage of prostate cancer may require
42 Prostate Cancer
different treatment strategies depending on an individual
patients life expectancy.
Staging system
The 7
th
edition Union Internationale Contre le Cancer (UICC)
2009 Tumour Node Metastasis (TNM) classification is used
for staging (Table 1).
Table 1: Tumour Node Metastasis (TNM) classification of
cancer of the prostate
T - Primary tumour
TX
T0
T1
T2
Primary tumour cannot be assessed
No evidence of primary tumour
Clinically unapparent tumour not palpable or visible
by imaging
T1a Tumour incidental histological finding in 5% or
less of tissue resected
T1b Tumour incidental histological finding in more
than 5% of tissue resected
T1c Tumour identified by needle biopsy (e.g.
because of elevated PSA level)
Tumour confined within the prostate
1
T2a Tumour involves one half of one lobe or less
T3
T4
T2b Tumour involves more than half of one lobe,
but not both lobes
T2c Tumour involves both lobes
Tumour extends through the prostatic capsule
2
T3a Extracapsular extension
(unilateral or bilateral)
T3b Tumour invades seminal vesicle(s)
Tumour is fixed or invades adjacent structures other
than seminal vesicles: external sphinter, rectum,
levator ani and/or pelvic wall
43 Prostate Cancer
N - Regional lymph nodes
3
NX
N0
N1
Regional lymph nodes cannot be assessed
No regional lymph node metastasis
Regional lymph node metastasis
M - Distant metastasis
4
M0
M1
No distant metastasis
Distant metastasis
M1a Non-regional lymph node(s)
M1b Bone(s)
M1c Other site(s)
1
Tumour found in one or both lobes by needle biopsy, but
not palpable or visible by imaging, is classified as T1c.
2
Invasion into the prostatic apex, or into (but not beyond)
the prostatic capsule, is not classified as T3, but as T2.
3
The regional lymph nodes are the nodes of the true pelvis,
which are essentially the pelvic nodes below the bifurca-
tion of the common iliac arteries. Laterality does not affect
the N classification.
4
When more than one site of metastasis is present, the
most advanced category should be used.
Gleason grading system
The most commonly used system for grading PCa is the
Gleason grading system.
Diagnosis and staging
The decision whether to proceed with further diagnostic or
staging work-up is guided by which treatment options are
available to the patient, taking the patients age and comor-
bidity into consideration. Procedures that will not affect the
treatment decision can usually be avoided.
Synoptic reporting of surgical specimens results in more
44 Prostate Cancer
transparent and more complete pathology reporting. The use
of a checklist is encouraged and two examples are presented
here.
Checklist for pathology reporting of prostate biopsies
1. Histological type of carcinoma
2. Histological grade (global or highest)
Primary grade
Secondary (= highest) grade
3. Fraction of involved cores
Number of cores involved by carcinoma
Total number of cores
4. Tumour quantification
Percentage of prostatic tissue involved by carcinoma or
total mm of cancer length
5. Tumour extent
Identification of perineural invasion
Identification of extra-prostatic extension
Identification of seminal vesicle invasion
Checklist for processing and pathology reporting of radical
prostatectomy (RP) specimens
1. Processing of RP specimens
Total embedding of a prostatectomy specimen is pre-
ferred, either by conventional (quadrant sectioning) or by
whole-mount sectioning
The entire surface of RP specimens should be inked
before cutting in order to evaluate the surgical margin
status
The apex should be separately examined using the cone
method with sagittal or radial sectioning
2. Histological type
3. Histological grade
Primary (predominant) grade
Secondary grade
45 Prostate Cancer
Tertiary grade (if exceeding > 5% of PCa volume)
Global Gleason score
Approximate percentage of Gleason grade 4 or 5 (option-
al)
4. Tumour quantification (optional)
Percentage of prostatic tissue involved
Tumour size of dominant nodule (if identified), greatest
dimension in mm
5. Pathological staging (pTNM)
Presence of extraprostatic extension (focal or extensive),
specify sites
Presence of seminal vesicle invasion
Presence of lymph node metastases, number of retrieved
lymph nodes and number of positive lymph nodes
6. Surgical margins
Presence of carcinoma at margin
If present, specify site(s) and extra- or intra-prostatic
invasion
7. Other
If identified, presence of angioinvasion
Location (site, zone) of dominant tumour (optional)
Perineural invasion (optional)
If present, specify extra- or intra-prostatic invasion
A short summary of the guidelines on diagnosis and staging of
PCa are presented below.
46 Prostate Cancer
Guidelines for the diagnosis and staging of PCa
Diagnosis of PCa GR
1. An abnormal digital rectal examination (DRE)
result or elevated serum PSA measurement
could indicate PCa. The exact cut-off level of
what is considered to be a normal PSA value has
yet to be determined, but values of approximate-
ly < 2-3 ng/mL are often used for younger men.
C
2. The diagnosis of PCa depends on histopathologi-
cal (or cytological) confirmation.
B
Biopsy and further staging investigations are
only indicated if they affect the management of
the patient.
C
3. Transrectal ultrasound (TRUS)-guided systemic
biopsy is the recommended method in most
cases of suspected PCa. At least 8 systemic,
laterally directed cores are recommended, with
perhaps more cores in larger volume prostates.
B
Transition zone biopsies are not recommended
in the first set of biopsies due to low detection
rates.
C
One set of repeat biopsies is warranted in cases
with persistent indication for PCa (abnormal
DRE, elevated PSA or histopathological findings
suggestive of malignancy at the initial biopsy).
B
Overall recommendations for further (three
or more) sets of biopsies cannot be made; the
decision must be made based on an individual
patient.
C
47 Prostate Cancer
4. Transrectal peri-prostatic injection with a local
anaesthetic can be offered to patients as effec-
tive analgesia when undergoing prostate biop-
sies.
A
Staging of PCa
1. Local staging (T-staging) of PCa should be based
on magnetic resonance imaging (MRI). Further
information is provided by the number and sites
of positive prostate biopsies, the tumour grade
and the level of serum PSA.
C
Despite its high specificity in the evaluation
of extraprostatic extension (EPE) and seminal
vesicle invasion or involvement (SVI), TRUS is
limited by poor contrast resolution, resulting in
low sensitivity and a tendency to understage
PCa. Even with the advent of colour- and
power Doppler to assist in identifying tumour
vascularity, the accuracy of TRUS in local
staging remains inadequate. In comparison
with DRE, TRUS and computed tomography
(CT), MRI demonstrates higher accuracy for
the assessment of uni- or bi-lobar disease
(T2), EPE and SVI (T3), as well as the invasion
of adjacent structures (T4). The addition of
dynamic contrast-enhanced MRI (DCE-MRI)
can be helpful in equivocal cases. The addition
of magnetic resonance spectroscopic imaging
(MRSI) to MRI also increases accuracy and
decreases inter-observer variability in the
evaluation of EPE.
C
48 Prostate Cancer
2. Lymph node status (N-staging) is only important
when potentially curative treatment is planned.
Patients with stage T2 or less, PSA < 20 ng/mL
and a Gleason score 6 have a lower than 10%
likelihood of having node metastases and can be
spared nodal evaluation.
B
Given the significant limitations of pre-operative
imaging in the detection of small metastases
(< 5 mm), pelvic lymph node dissection (PLND)
remains the only reliable staging method in
clinically localised PCa.
Currently, it seems that only methods of histo-
logical detection of lymph node metastases with
high sensitivity, such as sentinel lymph node
dissection or extended PLND, are suitable for
lymph node staging in PCa.
C
3. Skeletal metastasis (M-staging) is best assessed
by bone scan. This may not be indicated in
asymptomatic patients if the serum PSA level is
< 20 ng/mL in the presence of well or moderately
differentiated tumours.
B
In equivocal cases,
11
C-choline-,
18
F-flouride-PET/
CT or whole body MRI are an option.
C
Treatment of prostate cancer
An overview of the treatment options for patients with PCa,
subdivided by stage at diagnosis, is presented below. Due
to a lack of randomised controlled trials in PCa, one therapy
option cannot be considered superior to another. However,
based on the currently available literature, the following
recommendations can be made.
49 Prostate Cancer
Guidelines for the primary treatment of PCa
Stage Treatment Comment GR
T1a Watchful wait-
ing
Standard treatment for
Gleason score 6 and 7 aden-
ocarcinomas and < 10-year life
expectancy.
B
Active surveil-
lance
In patients with > 10-year life
expectancy, re-staging with
TRUS and biopsy is recom-
mended.
B
Radical pros-
tatectomy
Optional in younger patients
with a long life expectancy,
especially for Gleason score
7 adenocarcinomas
B
Radiotherapy Optional in younger patients
with a long life expectancy, in
particular in poorly differenti-
ated tumours. Higher compli-
cation risks after TURP, espe-
cially with interstitial radiation.
B
Hormonal Not an option. A
Combination Not an option. C
T1b-
T2b
Active surveil-
lance
Treatment option in patients
with cT1c-cT2a, PSA
< 10 ng/mL, biopsy Gleason
score 6, 2 biopsies positive,
50% cancer involvement of
each biopsy.
B
Patients with a life expectancy
< 10 years.
50 Prostate Cancer
Patients with a life expect-
ancy > 10 years once they are
informed about the lack of sur-
vival data beyond 10 years.
Patients who do not accept
treatment-related complica-
tions.
T1a-
T2c
Radical pros-
tatectomy
Optional in patients with pT1a
PCa.
A
Standard treatment for
patients with a life expectancy
> 10 years who accept treat-
ment-related complications.
Radiotherapy Patients with a life expectancy
> 10 years who accept treat-
ment-related complications.
B
Patients with contraindica-
tions for surgery.
Unfit patients with 5-10 years
of life expectancy and poorly
differentiated tumours (com-
bination therapy is recom-
mended; see below).
Brachytherapy Low-dose rate brachytherapy
can be considered for low risk
PCa patients with a prostate
volume 50 mL and an IPSS
12.
B
51 Prostate Cancer
Hormonal Symptomatic patients, who
need palliation of symptoms,
unfit for curative treatment.
C
Anti-androgens are associated
with a poorer outcome com-
pared to active surveillance
and are not recommended.
A
Combination For high-risk patients, neoadju-
vant hormonal treatment and
concomitant hormonal thera-
py plus radiotherapy results in
increased overall survival.
A
T3- T4 Watchful wait-
ing
Option in asymptomatic
patients with T3, well-differ-
entiated and moderately-dif-
ferentiated tumours, and a life
expectancy < 10 years who are
unfit for local treatment.
C
Radical pros-
tatectomy
Optional for selected patients
with T3a, PSA < 20 ng/mL,
biopsy Gleason score 8 and a
life expectancy > 10 years.
C
Patients have to be informed
that RP is associated with
an increased risk of positive
surgical margins, unfavourable
histology and positive lymph
nodes and that, therefore,
adjuvant or salvage therapy
such as radiation therapy or
androgen deprivation might be
indicated.
52 Prostate Cancer
Radiotherapy T3 with > 5-10 years of life
expectancy. Dose escalation
of > 74 Gy seems to be of
benefit. A combination with
hormonal therapy can be rec-
ommended (see below).
A
Hormonal Symptomatic patients, exten-
sive T3-T4, high PSA level
(> 25-50 ng/mL), PSA-Doubling
Time (DT) < 1 year.
Patient-driven, unfit patients.
Hormone monotherapy is not
an option for patients who are
fit enough for radiotherapy.
A
Combination Overall survival is improved
by concomitant and adjuvant
hormonal therapy (3 years)
combined with external beam
radiation.
A
NHT plus radical prostatec-
tomy: no indication.
B
53 Prostate Cancer
N+,
M0
Watchful wait-
ing
Asymptomatic patients.
Patient-driven (PSA
< 20-50 ng/mL), PSA DT > 12
months. Requires very close
follow-up.
B
Radical pros-
tatectomy
Optional for selected patients
with a life expectancy of > 10
years as part of a multimodal
treatment approach.
C
Radiotherapy Optional in selected patients
with a life expectancy of > 10
years, combination therapy
with adjuvant androgen dep-
rivation for 3 years is manda-
tory.
C
Hormonal Standard adjuvant therapy in
more than 2 positive nodes
to radiation therapy or radi-
cal prostatectomy as primary
local therapy. Hormonal ther-
apy should only be used as
monotherapy in patients who
are unfit for any type of local
therapy.
A
Combination No standard option.
Patient-driven.
B
M+ Watchful wait-
ing
No standard option. May have
worse survival/more complica-
tions than with immediate hor-
monal therapy. Requires very
close follow-up.
B
Radical pros-
tatectomy
Not a standard option. C
54 Prostate Cancer
Radiotherapy Not an option for curative
intent; therapeutic option in
combination with androgen
deprivation for treatment of
local cancer-derived symp-
toms.
C
Hormonal Standard option. Mandatory in
symptomatic patients.
A
For more detailed information and discussion on second-line
therapy, please see the full text version of the guidelines.
Follow-up of prostate cancer patients
Determination of serum PSA, disease-specific history and
DRE are the cornerstones in the follow-up of PCa patients.
Routine imaging procedures in stable patients are not recom-
mended and should only be used in specific situations.
Guidelines for follow-up after treatment with curative
intent
GR
In asymptomatic patients, a disease-specific history
and a serum PSA measurement supplemented by
DRE are the recommended tests for routine follow-up.
These should be performed at 3, 6 and 12 months after
treatment, then every 6 months until 3 years, and then
annually.
B
After RP, a serum PSA level > 0.2 ng/mL can be associ-
ated with residual or recurrent disease.
B
After radiation therapy, a rising PSA level > 2 ng/mL
above the nadir PSA, rather than a specific threshold
value, is the most reliable sign of persistent or recur-
rent disease.
B
Both a palpable nodule and a rising serum PSA level
can be signs of local disease recurrence.
B
55 Prostate Cancer
Detection of local recurrence by TRUS and biopsy is
only recommended if it will affect the treatment plan.
In most cases TRUS and biopsy are not necessary
before second-line therapy.
B
Metastasis may be detected by pelvic CT/MRI or bone
scan. In asymptomatic patients, these examinations
may be omitted if the serum PSA level is < 20 ng/mL.
C
Routine bone scans and other imaging studies are not
recommended in asymptomatic patients. If a patient
has bone pain, a bone scan should be considered irre-
spective of the serum PSA level.
B
Guidelines for follow-up after hormonal treatment GR
Patients should first be evaluated at 3 and 6 months
after treatment initiation. Tests should at least include
serum PSA measurement, DRE, serum testosterone
and careful evaluation of symptoms in order to assess
the treatment response and side-effects.
B
If patients undergo intermittent androgen deprivation,
PSA and testosterone should be monitored at 3 month
intervals during the treatment pause.
C
Follow-up should be tailored to the individual patient,
according to symptoms, prognostic factors and the
treatment given.
C
In patients with stage M0 disease with a good treat-
ment response, follow-up is scheduled every 6 months,
and should include at least a disease-specific history,
DRE and serum PSA measurement.
C
In patients with stage M1 disease with a good treat-
ment response, follow-up is scheduled for every 3 to 6
months. Follow-up should include at least a disease-
specific history, DRE and serum PSA measurement,
frequently supplemented with haemoglobin, serum
creatinine and alkaline phosphatase measurements.
C
56 Prostate Cancer
Patients (especially with M1b status) should be advised
about the clinical signs that could suggest spinal cord
compression.
A
Where disease progression occurs, or if the patient
does not respond to the treatment given, follow-up
needs to be individualised.
C
Routine imaging of stable patients is not recom-
mended.
B
Treatment of relapse after curative therapies
An effort should be made to distinguish between the probabil-
ity of local failure only versus distant (+/- local) failure. Initial
pathology, how long after primary therapy the PSA-relapse
occurs and how fast the PSA-value is rising can all aid in the
distinction between local and distant failure. Poorly differenti-
ated tumour, early PSA-relapse and a short PSA-doubling time
are all signs of distant failure. Treatment can then be guided
by the presumed site of failure, the patients general condition
and personal preferences. Imaging studies are of limited value
in patients with early PSA-relapse only.
57 Prostate Cancer
Guidelines for second-line therapy after curative
treatments
GR
Presumed
local failure
after radical
prostatec-
tomy
Only patients with presumed local
failure may be candidates for salvage
radiotherapy. This should be given
with at least 64 Gy and preferably
before PSA has risen above
0.5 ng/mL. Other patients are best
offered a period of active surveillance
(active monitoring), with possible hor-
monal therapy later on.
B
Presumed
local failure
after radio-
therapy
Selected patients may be candidates
for salvage RP and they should be
informed about the high risk of com-
plications, such as incontinence and
erectile dysfunction.
Salvage prostatectomy should only be
performed in experienced centres.
C
Other patients are best offered a
period of active surveillance (active
monitoring), with possible hormonal
therapy later on.
Presumed dis-
tant failure
There is some evidence that early hor-
monal therapy may be of benefit in +/-
local failure, delaying progression, and
possibly achieving a survival benefit
in comparison with delayed therapy.
The results are controversial. Local
therapy is not recommended except
for palliative reasons.
B
Treatment of relapse after hormonal therapy
Castration-refractory PCa (CRPC) is usually a debilitating
disease, often affecting elderly patients. A multidisciplinary
58 Prostate Cancer
approach is required with input from medical oncologists,
radiation oncologists, urologists, nurses, psychologists and
social workers. In most cases the decision whether to treat
or not is made based on counselling of the individual patient,
which limits the role of guidelines.
Guidelines for secondary hormonal management in
patients with CRPC
GR
Anti-androgen therapy should be stopped once PSA
progression is documented.
B
No clear-cut recommendation can be made for the
most effective drug for secondary hormonal manipula-
tions because data from randomised trials are scarce.
However, abiraterone and MDV3100 may address this
issue once final data from the prospective randomised
Phase III clinical trials are analysed.
C
Comment: An eventual anti-androgen withdrawal effect
should become apparent 4-6 weeks after the discontinuation
of flutamide or bicalutamide.
Guidelines for cytotoxic therapy in patients with
CRPC
GR
Patients with CRPC should be counselled, managed
and treated in a multidisciplinary team.
In non-metastatic CRPC, cytotoxic therapy should only
be used in a clinical trial setting.
B
In patients with a PSA rise, only two consecutive
increases of PSA serum levels above a previous refer-
ence level should be documented.
B
Prior to treatment, testosterone serum levels should
be below 32 ng/dL.
B
59 Prostate Cancer
Prior to treatment, PSA serum levels should be
> 2 ng/mL to assure correct interpretation of therapeu-
tic efficacy.
B
Potential benefits of cytotoxic therapy and expected
side-effects should be discussed with each individual
patient.
C
In patients with metastatic CRPC, who are candidates
for cytotoxic therapy, docetaxel at 75 mg/m
2
every 3
weeks is the drug of choice since it has shown a signifi-
cant survival benefit.
A
In patients with symptomatic osseous metastases
due to CRPC, either docetaxel or mitoxantrone with
prednisone or hydrocortisone are viable therapeutic
options. If not contraindicated, docetaxel is the pre-
ferred agent based on the significant advantage in pain
relief.
A
In patients with relapse following first-line docetaxel
chemotherapy, based on the results of prospective
randomised clinical phase III trials, Cabazitaxel and
Abiraterone are regarded as first-choice option for
second-line treatment.
A
Second-line docetaxel may be considered in previously
responding docetaxel-treated patients. Otherwise
treatment is to be tailored to the individual patients.
In case patients are not eligible for cabazitaxel or abi-
raterone, docetaxel is an option.
A
Guidelines for palliative management of patients with
CRPC
GR
Patients with symptomatic and extensive osseous
metastases cannot benefit from medical treatment
with regard to life prolongation.
A
Management of these patients has to be directed at
improving quality of life and providing pain reduction.
A
60 Prostate Cancer
Effective medical management with the highest effi-
cacy and a low frequency of side-effects is the major
goal of therapy.
A
Bisphosphonates (e.g. zoledronic acid) should be
offered to patients with skeletal masses to prevent
osseous complications. However, the benefits must be
balanced against the toxicity of these agents, in par-
ticular, jaw necrosis must be avoided.
A
Palliative treatments, such as radionuclides, external
beam radiotherapy, and adequate use of analgesics,
should be considered early on in the management of
painful osseous metastases.
B
Spinal surgery or decompressive radiotherapy are
emergency surgeries which have to be considered for
patients with neurological symptoms thought to be
critical.
A
Summary
Prostate cancer is a complex disease, in which many aspects
of the disease itself and the affected patient must be consid-
ered before decisions regarding diagnostic work-up, treat-
ment and follow-up can be made.
This short booklet text is based on the more comprehensive EAU
guidelines (ISBN 978-90-79754-83-0), available to all members of the
European Association of Urology at their website,
http://www.uroweb.org.
78 Penile Cancer
GUIDELINES ON PENILE CANCER
(Text update April 2010)
G. Pizzocaro, F. Algaba, S. Horenblas, E. Solsona, S. Tana,
H. Van Der Poel, N. Watkin
Eur Urol 2010 Jun;57(6):1002-12
Introduction
Over recent years, the cure rate for penile cancer has risen to
80% because of improved knowledge of the disease, earlier
diagnosis, technological advances, and specialist treatment in
centres of excellence.
In Western countries, primary malignant penile cancer is
uncommon, with an overall incidence of less than 1.00 per
100,000 males in Europe and the United States of America
(USA). Incidence also varies according to racial group, eth-
nicity, and geographical location. Social and cultural habits,
hygienic and religious practices interfere significantly with
risk factors.
Since a few years, there has been a well-documented associa-
tion between human papillomavirus (HPV) and squamous
cell carcinoma (SCC). Vaccination is available for very young
females against HPV strains responsible for most cases of
cervical cancer. Vaccination will be considered in males
according to the results in females.
Classification and pathology
The new, 2009, Tumour Node Metastasis (TNM) classification
for penile cancer includes a change for the T1 category (Table
1). This classification needs a further update for the definition
of the T2 category*.
79 Penile Cancer
Table 1: 2009 TNM staging classification
T - Primary tumour
TX
T0
Tis
Ta
T1
T2*

T3
T4
Primary tumour cannot be assessed
No evidence of primary tumour
Carcinoma in situ
Non-invasive verrucous carcinoma, not associated
with destructive invasion
Tumour invades subepithelial connective tissue
T1a without lymphovascular invasion and well or
moderately differentiated (T1G1-2)
T1b with lymphovascular invasion or poorly differen-
tiated/undifferentiated (T1G3-4)
Tumour invades corpus spongiosum/corpora
cavernosa
Tumour invades urethra
Tumour invades other adjacent structures
N - Regional lymph nodes
NX
N0
N1
N2
N3
Regional lymph nodes cannot be assessed
No palpable or visibly enlarged inguinal lymph node
Palpable mobile unilateral inguinal lymph node
Palpable mobile multiple or bilateral inguinal lymph
nodes
Fixed inguinal nodal mass or pelvic lymphadenopa-
thy, unilateral or bilateral
M - Distant metastasis
M0
M1
No distant metastasis
Distant metastasis
TNM pathological classification
The pT categories correspond to the T categories. The pN
categories are based upon biopsy, or surgical excision.
80 Penile Cancer
Table 2: 2009 TNM pathological classification
pN - Regional lymph nodes
pNX
pN0
pN1
pN2
pN3
Regional lymph nodes cannot be assessed
No regional lymph node metastasis
Intranodal metastasis in a single inguinal lymph node
Metastasis in multiple or bilateral inguinal lymph
nodes
Metastasis in pelvic lymph node(s), unilateral or
bilateral or extranodal extension of regional lymph
node metastasis
pM - Distant metastasis
pM0
pM1
No distant metastasis
Distant metastasis
G - Histopathological grading
Gx
G1
G2
G3-4
Grade of differentiation cannot be assessed
Well differentiated
Moderately differentiated
Poorly differentiated/undifferentiated
Pathology
Squamous cell carcinoma accounts for more than 95% of
cases of malignant penile disease. Table 3 lists premalignant
lesions and Table 4 lists the different types of penile SCC
neoplasia.
Table 3: Premalignant lesions
Lesions sporadically associated with SCC of the penis
Cutaneous horn of the penis
Bowenoid papulosis of the penis
Lesion at intermediate risk
Balanitis xerotica obliterans
(lichen sclerosus et atrophicus)
81 Penile Cancer
Lesions at high risk of developing SCC of the penis (up to
one-third transform to invasive SCC)
Penile intraepithelial neoplasia (carcinoma in situ)
Erythroplasia of Queyrat and Bowens disease
Table 4: Pathologic classification of SCC of the penis
Types of SCC
Classic
Basaloid
Verrucous and its varieties: warty (condylomatous) carci-
noma; verrucous carcinoma; papillary carcinoma; hybrid
verrucous carcinoma; and mixed carcinomas (warty
basaloid, adenobasaloid carcinoma)
Sarcomatoid
Adenosquamous
Growth patterns of SCC
Superficial spread
Nodular or vertical-phase growth
Verrucous
Differentiation grading systems for SCC
Broders grading system
Maiches system score
Diagnosis
Accurate histological diagnosis and staging of both the
primary tumour and regional nodes are a prerequisite before
making treatment decisions (Table 5).
Biopsy
The need for histological confirmation is dependent on:
doubt about the exact nature of the lesion;
treatment of the lymph nodes based on pre-operative
histology.
82 Penile Cancer
In these cases an adequate biopsy is advised. Although a
punch biopsy may be sufficient for superficial lesions, but an
excisional one is preferred. There is no need for biopsy if:
there is no doubt about the diagnosis;
treatment of the lymph nodes is postponed after treat-
ment of the primary tumour and/or after histological
examinations of the sentinel node(s).
Physical examination
The physical examination of suspected penile cancer must
record:
diameter of the penile lesion(s) or suspicious areas;
location of lesion(s) on the penis;
number of lesions;
morphology of lesion(s): papillary, nodular, ulcerous or flat;
relationship of lesion(s) to other structures, e.g. submu-
cosa, tunica albuginea, urethra, corpus spongiosum and
corpus cavernosum;
colour and boundaries of lesion(s);
penile length.
Imaging
Physical examination is reliable in determining infiltration into
the corpora. If doubt exists on depth of infiltration or proximal
extension, magnetic resonance imaging (MRI) may be helpful
on erect penis ( prostaglandin E1 injection).
83 Penile Cancer
Table 5: Guidelines for the diagnosis of penile cancer GR
Primary tumour C
Physical examination, recording morphological and
physical characteristics of the lesion.
Cytological and/or histological diagnosis.
Inguinal lymph nodes C
Physical examination of both groins, recording
nodal morphological and physical characteristics.
If nodes are non-palpable, DSNB is indicated; if
DSNB is not available, ultrasound-guided FNAC/risk
factors.
If nodes are palpable, FNAC for cytological
diagnosis.
Regional metastases (inguinal and pelvic nodes) C
A pelvic CT, PET/CT is indicated in patients with
metastatic inguinal nodes.
Distant metastases (beside inguinal and pelvic nodes) C
PET/CT also allows evidence of distant metastasis.
If PET/CT is not available, abdominal CT and plain
radiography chest are advisable, and in sympto-
matic M1 patients a bone scan is also advisable.
Biological laboratory determinations for penile
cancer are investigational and not for clinical use.
C
CT = computed tomography; DNSB = dynamic sentinel node
biopsy; GR = grade of recommendation; FNAC = fine-needle
aspiration cytology; PET = positron emission tomography.
Treatment
The primary tumour and regional lymph nodes are usually
treated separately (Table 6). Correct staging is crucial for
accurate treatment. Lymphadenectomy (LAD) is mandatory
for patients with evidence of inguinal lymph node metastases.
84 Penile Cancer
Table 6: Guidance on treatment strategies for penile cancer
Primary tumour Conservative treatment is to
be considered whenever
possible
LE GR
Category Tis, Ta,
T1a (G1, G2)
CO
2
or Nd:YAG laser surgery,
wide local excision, glans
resurfacing, or glans resection,
depending on size and location
of the tumour
2b B
Mohs micrographic surgery
or photodynamic therapy for
well differentiated superficial
lesions (Tis, G1, Ta)
3 C
Categories:
T1b (G3) and T2
(glans only)
Glansectomy, with or without
tips amputation or recon-
struction
2b B
Category T2
(invasion of the
corpora)
Partial amputation 2b B
Category T3
invasion of ure-
thra
Total amputation with perineal
urethrostomy
2b B
Category T4
(other adj. struc-
tures)
Eligible patients: neoadjuvant
chemotherapy followed by
surgery in responders.
Alternative: external radiation
3 C
Local disease
recurrence after
conservative
therapy
Salvage surgery, consisting
of penis-sparing treatment in
small recurrences
3 C
Larger recurrence: some form
of amputation
2b B
85 Penile Cancer
Radiotherapy Organ-preserving treatment in
selected patients with Tl-2 of
glans or coronal sulcus, lesions
< 4 cm
2b B
Chemotherapy Neo adjuvant, before surgery 3 C
Palliation in advanced or meta-
static disease
3 C
CO
2
= carbon dioxide; Nd:YAG = neodymium:yttrium-alumi-
nium-garnet.
Table 7: Guidance on treatment strategies for regional
lymph nodes in penile cancer
Regional
lymph nodes
Management of regional lymph
nodes is fundamental
LE GR
No palpable
inguinal
nodes
Tis, Ta G1, T1G1: surveillance 2a B
> T1G2: DSNB
(NB: Inguinal LAD if histology is
positive)
2a B
If DSNB not available: risk factors/
nomogram decision-making
3 C
Palpable
inguinal
nodes
US-guided FNAB (DSNB is unsuit-
able for palpable nodes)
2a B
Negative biopsy: surveillance
(repeat biopsy)
Positive biopsy: inguinal LAD on
positive side
(NB: Modified LAD must include
the central zone and both supe-
rior Daselers zones)
86 Penile Cancer
Pelvic nodes Pelvic LAD if there is: extran-
odal metastasis; Cloquet node
involved; > 2 inguinal node metas-
tases
2a B
Unilateral pelvic LAD if unilateral
lymph node metastases with pro-
longed inguinal incision
2b B
Bilateral pelvic LAD if bilateral
inguinal metastases
2a B
Adjuvant
chemo-
therapy
In patients with > 1 intranodal
metastasis (pN2 pN3) after radi-
cal LAD, survival is improved
by adjuvant chemotherapy (3
courses of cisplatin, fluorouracil
[PF] chemotherapy)
2b B
Table 8: Follow-up schedule for penile cancer
Interval of follow-up Examinations and
investigations
Maximum duration
of follow-up
GR
Years 1 and 2 Years 3, 4 and 5
Recommendations for follow-up of the primary tumour
Penile preserving treat-
ment
3 months 6 months Regular physician or self-
examination
5 years C
Amputation 6 months 1 year Regular physician or self-
examination
5 years C
Recommendations for follow-up of the inguinal lymph nodes
Wait-and-see 3 months 6 months Regular physician or self-
examination
5 years C
pN0 6 months 1 year Regular physician or self-
examination
Ultrasound with FNAB
5 years C
pN+ 3 months 6 months Regular physician or self-
examination
Ultrasound with FNAB
5 years C
87 Penile Cancer
Patients with
fixed or
relapsed
inguinal
nodes
Neo-adjuvant chemotherapy
is strongly recommended in
patients with unresectable or
recurrent lymph node metastases
2a B
Taxanes seem to improve the
efficacy of standard PF chemo-
therapy (or carboplatin)
Radiotherapy Curative radiotherapy may be
used for palliation in primary
tumours of the glans penis and
sulcus < 4 cm or
2a B
Prophylactic radiotherapy in clini-
cal N0 patients is not indicated
2a B
LAD = lymphadenectomy; FNAB = fine-needle aspiration biop-
sy; DSNB = sentinel node biopsy.
Table 8: Follow-up schedule for penile cancer
Interval of follow-up Examinations and
investigations
Maximum duration
of follow-up
GR
Years 1 and 2 Years 3, 4 and 5
Recommendations for follow-up of the primary tumour
Penile preserving treat-
ment
3 months 6 months Regular physician or self-
examination
5 years C
Amputation 6 months 1 year Regular physician or self-
examination
5 years C
Recommendations for follow-up of the inguinal lymph nodes
Wait-and-see 3 months 6 months Regular physician or self-
examination
5 years C
pN0 6 months 1 year Regular physician or self-
examination
Ultrasound with FNAB
5 years C
pN+ 3 months 6 months Regular physician or self-
examination
Ultrasound with FNAB
5 years C
88 Penile Cancer
Follow-up
The aim of follow-up is to detect local and/or regional recur-
rences at an early curable stage. Metastases at distant
sites are fatal. Risk stratification for recurrence is helpful.
Traditional follow-up methods have been inspection and
physical evaluation.
Modern US or PET/CT are useful adjuncts. The follow-up
interval and strategies for patients with penile cancer are
guided by the initial treatment of the primary lesion and
regional lymph nodes (Table 7). About 92% of all recurrences
occur within 5 years and they may be neo-occurrences.
Follow-up can stop after 5 years in well educated and moti-
vated patients able to perform self-examination.
Quality of life
As more people achieve long-term survival after cancer, sexual
dysfunction and infertility are increasingly recognised as nega-
tive consequences. Penile-sparing surgery allows a better
quality of life than penectomy and must be considered when-
ever feasible. Psychological support should be offered at a low
threshold.
This short booklet text is based on the more comprehensive EAU
guidelines (ISBN 978-90-79754-70-0), available to all members of the
European Association of Urology at their website,
http://www.uroweb.org.
89 Testicular Cancer
GUIDELINES ON TESTICULAR CANCER
(Limited text update March 2011)
P. Albers (chair), W. Albrecht, F. Algaba, C. Bokemeyer,
G. Cohn-Cedermark, K. Fizazi, A. Horwich, M.P. Laguna
Eur Urol 2008 Mar;53(3):478-96,497-513
Eur Urol 2011 Aug;60(2):304-19
Introduction
Compared with other types of cancer, testicular cancer is
relatively rare accounting for approximately 1-1.5% of all
cancers in men.
A steady increase in incidence has been seen over the past
decades in the industrialised countries. The majority of these
tumours are derived from germ cells (seminoma and non-
seminoma germ cell testicular cancer) and more than 70% of
patients are diagnosed with stage I disease. Nowadays tes-
ticular tumours show excellent cure rates, mainly due to early
diagnosis and their extreme chemo- and radiosensitivity.
Table 1: Prognostic risk factors for the development of
tumours
Epidemiological risk factors
History of cryptorchidism
Klinefelters syndrome
Familial history of testis cancer in first-grade relatives
Presence of contralateral tumour
Tin or infertility
90 Testicular Cancer
Pathological prognostic risk factors for occult metastatic
disease (for stage I)
For seminoma (not prospectively evaluated)
- Tumour size 4 cm)
- Invasion of the rete testis
For non-seminoma
- Vascular/lymphatic invasion or peri-tumoural invasion
- Proliferation rate (MIB-1) > 70%
- Percentage embryonal carcinoma > 50%
Clinical (for metastatic disease)
Primary location
Elevation of tumour marker levels
Presence of non-pulmonary visceral metastasis
Classification
Testicular epithelial cancer is classified into three categories:
(a) germ cell tumours;
(b) sex cord stromal tumours;
(c) miscellaneous germ cell/sex cord stromal tumours.
Germ cell tumours account for 90-95% of cases of testicular
cancer according to the WHO classification system.
Table 2: The recommended pathological classification
(modified World Health Organization 2004)
1. Germ cell tumours
Intratubular germ cell neoplasia
Seminoma (including cases with syncytiotrophoblastic cells)
Spermatocytic seminoma (mention if there is a sarcomatous
component)
Embryonal carcinoma
Yolk sac tumour
Choriocarcinoma
91 Testicular Cancer
Teratoma (mature, immature, with malignant component)
Tumours with more than one histological type
(specify % of individual components)
2. Sex cord/gonadal stromal tumours
Leydig cell tumour
Malignant Leydig cell tumour
Sertoli cell tumour (lipid-rich variant, sclerosing, large cell
calcifying)
Malignant Sertoli cell tumour
Granulosa (adult and juvenile)
Thecoma/fibroma group of tumours
Other sex cord/gonadal stromal tumours
(incompletely differentiated, mixed)
Tumours containing germ cell and sex cord/gonadal stromal
(gonadoblastoma)
3. Miscellaneous non-specific stromal tumours
Ovarian epithelial tumours
Tumours of the collecting ducts and rete testis
Tumours (benign and malignant) of non-specific stroma
Diagnosis of testicular cancer
The diagnosis of testicular cancer is based on:
Clinical examination of the testis and general examination to
rule out enlarged nodes or abdominal masses.
Ultrasound (US) of both testes should be performed whenever
a testicular tumour is suspected. An additional US of the
retroperitoneum is recommended to screen for extensive
retroperitoneal metastasis. Ultrasound of both testes should
also be performed in patients with a retroperitoneal mass
and/or elevated tumour serum markers without a palpable
scrotal mass.
92 Testicular Cancer
Serum tumour markers, both before, and 5-7 days after
orchiectomy (AFP and hCG) and LDH. The latter is mandatory
in advanced tumours.
Inguinal exploration and orchiectomy with en bloc removal of
testis, tunica albuginea, and spermatic cord. If the diagnosis
is not clear, a testicular biopsy (tumour enucleation) is to be
taken for histopathological frozen section.
Organ-sparing surgery can be attempted in special cases
(bilateral tumour or solitary testes). Routine contralateral
biopsy for diagnosis of carcinoma in situ should be discussed
with the patient and is recommended in high risk patients
(testicular volume < 12 mL, a history of cryptorchidism and
age under 40 years).
Diagnosis and treatment of Tin
Biopsy should be offered to patients with high risk for contra-
lateral Tin (testicular volume < 12 mL, history of cryptorchidism
or poor spermatogenesis). If performed, a double biopsy is
preferred. In case of Tin, local radiotherapy is is indicated
following counselling on impaired testosterone production
and infertility.
Staging of testicular tumours
For an accurate staging the following steps are necessary:
Postorchiectomy half-life kinetics of serum tumour markers.
The persistence of elevated serum tumour markers after
orchiectomy may indicate the presence of disease, while its
normalisation does not necessarily mean absence of tumour.
Tumour markers should be assessed until they are normal, as
long as they follow their half-life kinetics and no metastases
are revealed.
Assessment of retroperitoneal and mediastinal nodes and
93 Testicular Cancer
viscera by abdominal CT and thoracic CT/plain radiography
chest. Supraclavicular nodes are to be assessed by physical
examination. MRI is helpful only when the above are incon-
clusive or in patients with an allergy to contrast agents. Other
examinations such as brain or spinal CT, bone scan or liver US
should be performed if metastases are suspected.
In patients diagnosed with testicular seminoma and a positive
abdominopelvic CT, a chest CT is recommended.
A chest CT scan should be routinely performed in patients
diagnosed with non-seminomatous germ cell tumours
(NSGCT) because in up to 10% of cases, small subpleural
nodes may be present that are not visible radiologically.
Staging system
The Tumour, Node, Metastasis (TNM 2009) staging system is
endorsed.
Table 3: TNM classification for testicular cancer
pT - Primary tumour
1
pTX
pT0
pTis
pT1
pT2
pT3
pT4
Primary tumour cannot be assessed
No evidence of primary tumour (e.g. histologic scar
in testis)
Intratubular germ cell neoplasia (testicular
intraepithelial neoplasia)
Tumour limited to testis and epididymis without
vascular/lymphatic invasion: tumour may invade
tunica albuginea but not tunica vaginalis
Tumour limited to testis and epididymis with vascu-
lar/lymphatic invasion, or tumour extending through
tunica albuginea with involvement of tunica vaginalis
Tumour invades spermatic cord with or without
vascular/lymphatic invasion
Tumour invades scrotum with or without vascular/
lymphatic invasion
94 Testicular Cancer
N - Regional lymph nodes clinical
NX
N0
Regional lymph nodes cannot be assessed
No regional lymph node metastasis
N1
N2
N3
Metastasis with a lymph node mass 2 cm in
greatest dimension, or multiple lymph nodes, none
> 2 cm in greatest dimension
Metastasis with a lymph node mass > 2 cm but 5
cm in greatest dimension, or multiple lymph nodes,
any one mass > 2 cm but 5 cm in greatest
dimension
Metastasis with a lymph node mass > 5 cm in
greatest dimension
pN - Pathological regional lymph nodes
pNX
pN0
pN1
pN2
pN3
Regional lymph nodes cannot be assessed
No regional lymph node metastasis
Metastasis with a lymph node mass 2 cm in
greatest dimension and 5 or fewer positive nodes,
none > 2 cm in greatest dimension
Metastasis with a lymph node mass > 2 cm but
< 5 cm in greatest dimension; or > 5 nodes positive,
none > 5 cm; or evidence of extranodal extension of
tumour
Metastasis with a lymph node mass > 5 cm in
greatest dimension
M - Distant metastasis
MX
M0
M1
M1a
M1b
Distant metastasis cannot be assessed
No distant metastasis
Distant metastasis
Non-regional lymph node(s) or lung
Other sites
pM - Pathological distant metastasis
The pM category corresponds to the M category
95 Testicular Cancer
S - Serum tumour markers
Sx
S0
Serum markers studies not available or not
performed
Serum marker study levels within normal limits
LDH (U/L) hCG (mlU/mL) AFP (ng/mL)
S1 < 1.5 x N and < 5,000 and < 1,000
S2 1.5-10 x N or 5,000-50,000 or 1,000-10,000
S3 > 10 x N or > 50,000 or > 10,000
1
Except for pTis and pT4, where radical orchiectomy is not
always necessary for classification purposes, the extent of the
primary tumour is classified after radical orchiectomy; see pT.
In other circumstances, TX is used if no radical orchiectomy
has been performed.
The International Germ Cell Cancer Collaborative Group
(IGCCCG) defined a prognostic factor-based staging system
for metastatic germ cell cancer that includes good and
intermediate prognosis seminoma and good, intermediate,
and poor prognosis NSGCT.
96 Testicular Cancer
Table 4: Prognostic-based staging system for metastatic
germ cell cancer (IGCCCG)
Good-prognosis group
Non-seminoma (56% of
cases)
All of the following criteria:
5-year PFS 89%
5-year survival 92%
Testis/retroperitoneal primary
No non-pulmonary visceral
metastases
AFP < 1,000 ng/mL
hCG < 5,000 IU/L (1,000 ng/mL)
LDH < 1.5 x ULN
Seminoma
(90% of cases)
All of the following criteria:
5-year PFS 82%
5-year survival 86%
Any primary site
No non-pulmonary visceral
metastases
Normal AFP
Any hCG
Any LDH
Intermediate-prognosis group
Non-seminoma
(28% of cases)
All of the following criteria:
5-year PFS 75%
5-year survival 80%
Testis/retroperitoneal primary
No non-pulmonary visceral
metastases
AFP 1,000 - 10,000 ng/mL or
hCG 5,000 - 50,000 IU/L or
LDH 1.5 - 10 x ULN
Seminoma
(10% of cases)
All of the following criteria:
97 Testicular Cancer
5-year PFS 67%
5-year survival 72%
Any primary site
Non-pulmonary visceral
metastases
Normal AFP
Any hCG
Any LDH
Poor-prognosis group
Non-seminoma
(16% of cases)
Any of the following criteria:
5-year PFS 41%
5-year survival 48%
Mediastinal primary
Non-pulmonary visceral
metastases
AFP > 10,000 ng/mL or
hCG > 50,000 IU/L
(10,000 ng/mL) or
LDH > 10 x ULN
Seminoma No patients classified as poor
prognosis
PFS = progression-free survival; AFP = alpha-fetoprotein;
hCG = beta-human chorionic gonadotrophin; LDH = lactate
dehydrogenase; ULN = upper limit of normal range.
Guidelines for the diagnosis and staging of testicular
cancer GR
Testicular US is mandatory. A
Orchidectomy and pathological examination of the
testis is necessary to confirm the diagnosis and to
define the local extension (pT category). In a life-
threatening situation due to extensive metastasis,
chemotherapy has to be started before orchidectomy.
A
Serum determination of tumour markers (AFP, hCG,
and LDH) must be performed before and after
orchidectomy for staging and prognostic reasons.
A
98 Testicular Cancer
The state of the retroperitoneal, mediastinal, and
supraclavicular nodes and visceral state must be
assessed in testicular cancer.
A
AFP = alpha-fetoprotein; hCG = human chorionic gonado-
trophin; LDH = lactate dehydrogenase.
Pathological examination of the testis
Following orchiectomy, the pathological examination of the
testis should include a number of investigations.
1. Macroscopic features: side, testis size, maximum tumour
size and macroscopic features of epididymis, spermatic
cord and tunica vaginalis.
2. Sampling: 1 cm
2
section for every centimetre of maximum
tumour diameter, including normal macroscopic paren-
chyma (if present), albuginea and epididymis with selection
of suspected areas. At least one proximal and one distal
section of the spermatic cord plus any suspected area.
3. Microscopic features and diagnosis:
histological type (specify individual components and
estimate amount as a percentage);
presence or absence of peri-tumoural venous and/or
lymphatic invasion;
presence or absence of albuginea, tunica vaginalis,
rete testis, epididymis or spermatic cord invasion, and;
presence or absence of intratubular germinal neo-
plasia (Tin) in non-tumoural parenchyma intratubular
germ cell neoplasia.
4. pT category according to TNM 2009.
5. Immunohistochemical studies: in seminoma and mixed
germ cell tumour, AFP and hCG.
99 Testicular Cancer
Guidelines for the treatment of testicular cancer
Seminoma stage I GR
Surveillance is the recommended management option
(if facilities available and patient compliant).
A
Carboplatin-based chemotherapy (one course at AUC
7) can be recommended.
B
Adjuvant treatment is not recommended for patients
at low risk.
A
Radiotherapy is not recommended as adjuvant treat-
ment.
A
NSGCT stage I GR
CS1 risk-adapted treatments based on vascular
invasion or surveillance without using risk factors are
recommended treatment options.
A
Risk-adapted treatments for CS1 based on vascular
invasion
CS1A (pT1, no vascular invasion): low risk
1. If the patient is willing and able to comply with a
surveillance policy, long-term (at least 5 years) close
follow-up should be recommended.
A
2. In low-risk patients not willing (or suitable) to
undergo surveillance, adjuvant chemotherapy or
nerve-sparing RPLND are treatment options
If RPLND reveals PN+ (nodal involvement) disease,
chemotherapy with two courses of PEB should be
considered.
A
CS1B (pT2-pT4): high risk
1. Primary chemotherapy with two courses of PEB
should be recommended (one course of PEB within a
clinical trial or registry).
A
100 Testicular Cancer
2. Surveillance or nerve-sparing RPLND in high-risk
patients remain options for those not willing to
undergo adjuvant chemotherapy.
If pathological stage II is revealed at RPLND, further
chemotherapy should be considered.
A
Guidelines for the treatment of metastatic germ cell
tumours
GR
1. Low volume NSGCT stage IIA/B with elevated
markers should be treated like good or intermedi-
ate prognosis advanced NSGCT, with three or four
cycles of PEB.
A
2. In stage IIA/B without marker elevation, histology
can be gained by RPLND or biopsy. A repeat
staging can be performed after six weeks of surveil-
lance before final decision on further treatment.
B
3. In metastatic NSGCT (> stage IIC) with a good
prognosis, three courses of PEB is the primary
treatment of choice.
A
4. In metastatic NSGCT with an intermediate or poor
prognosis, the primary treatment of choice is four
courses of standard PEB and inclusion in clinical
trials is strongly recommended.
A
5. Surgical resection of residual masses after
chemotherapy in NSGCT is indicated in the case of
visible residual masses and when serum levels of
tumour markers are normal or normalising.
A
6. Seminoma CS IIA/B can initially be treated with
radiotherapy. When necessary, chemotherapy
can be used as a salvage treatment with the same
schedule as for the corresponding prognostic
groups of NSGCT.
A
101 Testicular Cancer
7. In seminoma stage CS IIB, chemotherapy (4 x EP or
3 x PEB, in good prognosis) is an alternative to
radiotherapy. It appears that 4 x EP or 3 x PEB
achieve a similar level of disease control.
B
8. Seminoma stage IIC and higher should be treated
with primary chemotherapy according to the same
principles used for NSGCT.
A
EP = eposide, cisplatin; NSGCT = non-seminomatous germ cell
tumour; PEB = cisplatin, eposide, bleomycin;
RPLND = retroperitoneal lymph node dissection.
Relapse after chemotherapy
The treatment of relapsed GCT after chemotherapy is
typically salvage chemotherapy. For patients at first relapse
with good prognostic features (initial achievement of CR/PR
M- and gonadal primary tumour) 4 cycles of standard dose
salvage chemotherapy are proposed. For patients with poor
prognostic factors (extragonadal primary and/or incomplete
response to first line chemotherapy) and for all patients with
subsequent (> first) relapse, high-dose chemotherapy with
autologous stem cell support is recommended.
Follow-up of patients with testicular cancer
The aim of the follow-up is to detect relapse as early as
possible and to monitor the contralateral testis. In the
presence of a curative- or life prolongation therapy, the
following principles should apply;
(a) interval between examinations and duration of follow-up
should be consistent with the time of maximal risk of
recurrence;
(b) tests should be directed at the most likely sites of
recurrence and have a good accuracy;
(c) the increased risk of second malignancy, both in the
primary site and in other tissues that may have been
exposed to the same carcinogens, or in which there is
102 Testicular Cancer
epidemiological evidence of increased risk, should also
guide the selection of tests;
(d) non-malignant complications of therapy must also be
considered.
Table 5: Recommended minimum follow-up schedule in a
surveillance policy: stage I non-seminoma
Procedure Year 1 Year 2 Year 3-5 Year 6-10
Physical
examination
4 times 4 times Once/yr. Once/yr.
Tumour markers 4 times 4 times Once/yr. Once/yr.
Plain radio-
graphy chest
Twice Twice
Abdominopelvic
CT
Twice
(at 3 and
12 mo)
CT = computed tomography.
Table 6: Recommended minimum follow-up schedule after
RPLND or adjuvant chemotherapy:
stage I non-seminoma
Procedure Year 1 Year 2 Year 3-5 Year 6-10
Physical
examination
4 times 4 times Once/yr. Once/yr.
Tumour markers 4 times 4 times Once/yr. Once/yr.
Plain radio-
graphy chest
Twice Twice
Abdominopelvic
CT
Once Once
CT = computed tomography.
103 Testicular Cancer
Table 7: Recommended minimum follow-up schedule for
post-orchidectomy surveillance, radiotherapy or
chemotherapy: stage I seminoma
Procedure Year 1 Year 2 Year 3 Year 4-5
Physical
examination
3 times 3 times Once/yr. Once/yr.
Tumour markers 3 times 3 times Once/yr. Once/yr.
Plain radio-
graphy chest
Twice Twice
Abdominopelvic
CT
Twice Twice
CT = computed tomography.
Table 8: Recommended minimum follow-up in advanced
NSGCT and seminoma
Procedure Year 1 Year 2 Year 3-5 thereafter
Physical
examination
4 times 4 times Twice/yr. Once/yr.
Tumour markers 4 times 4 times Twice/yr. Once/yr.
Plain radio-
graphy chest
4 times 4 times Twice/yr. Once/yr.
Abdominopelvic
CT*

Twice Twice As indi-


cated
As indi-
cated
Chest CT As indi-
cated
As indi-
cated
As indi-
cated
As indi-
cated
Brain CT As indi-
cated
As indi-
cated
As indi-
cated
As indi-
cated
104 Testicular Cancer
* Abdominal CT must be performed at least annually if
teratoma is found in the retroperitoneum.

If the post-chemotherapy evaluation in a seminoma


patient shows any mass > 3 cm, the appropriate CT should
be repeated 2 and 4 months later to ensure that the mass
is continuing to regress. If available, FDG-PET/CT can be
performed.

A chest CT is indicated if abnormality is detected on plain


radiography chest and after pulmonary resection.

In patients with headaches, focal neurological findings, or


any central nervous system symptoms.
CT = computed tomography; FDG-PET/CT = fluorodeoxyglu-
cose-positron emission tomography computed tomography.
Testicular stromal tumours
Testicular stromal tumours are rare, however, Leydig cell and
Sertoli cell tumours are of clinical relevance.
Leydig cell tumours
Leydig cell tumours constitute 1-3% of adult testicular
tumours and 3% of testicular tumours in children. Only about
10% of them are malignant presenting the following features:
Large size (> 5 cm);
Cytologic atypia and DNA aneuploidy;
Increased mitotic activity and increased MIB -1 expression;
Necrosis;
Vascular invasion infiltrative margins;
Extension beyond the testicular parenchyma.
The tumour presents as a painless enlarged testis or as an
incidental ultrasound finding accompanied in up to 80% of
cases by hormonal disorders. Serum tumour markers are
negative and approximately 30% of patients present with
gynaecomastia. These tumours are often treated by inguinal
105 Testicular Cancer
orchiectomy because they are misinterpreted as germ cell
tumours.
Especially in patients with symptoms of gynaecomastia
or hormonal disorders or typical imaging on ultrasound, until
final histology is available, a partial orchiectomy (+ frozen
section) should be considered. In case of histological signs
of malignancy orchiectomy and RPLND are the treatment of
choice.
Sertoli cell tumours
They are even rarer than Leydig cell tumours, and they are
malignant in 10-22% of cases. Morphological signs of
malignancy are:
Large size (> 5 cm);
Pleomorphic nuclei with nucleoli;
Increased mitotic activity;
Necrosis and vascular invasion.
They present either as an enlarged testis or as incidental
ultrasound finding. Hormonal disorders are infrequent and
serum tumour markers are negative.
Ultrasonographically they generally appear as hypoechoic
and cannot be safely distinguished from germ-cell tumour
except for the subtype large cell calcifying form which is
usually associated with genetic syndromes (Carneys com-
plex, Peutz-Jeghers syndrome). Sertoli cell tumours are often
interpreted as germ-cell tumours and an orchiectomy is
performed.
Organ-sparing surgery should be considered (with caution)
but in case of histological signs of malignancy orchiectomy
and RPLND are the treatment of choice.
Conclusions
Most testis tumours derive from germ cells and are diagnosed
at an early stage. Staging is the cornerstone and the 2009
106 Testicular Cancer
TNM system is recommended for classification and staging
purposes.
The IGCCCG staging system is recommended for metastatic
disease. Following orchiectomy, excellent cure rates are
achieved for those early stages irrespective of the
treatment policy adopted, although pattern and relapse
rates are closely linked to the treatment modality chosen. In
metastatic disease a multidisciplinary therapeutic approach
offers an acceptable survival. Follow-up schedules should be
tailored to initial staging and treatment. Testicular stromal
tumours are rare and usually benign. When suspected and
pathologically confirmed they can be treated by organ sparing
surgery. However, in case of malignancy (small percentage)
orchiectomy and RPLND are the treatment of choice.
This short booklet text is based on the more comprehensive EAU
guidelines (ISBN 978-90-79754-96-0), available to all members of the
European Association of Urology at their website,
http://www.uroweb.org.
107 Male Lower Urinary Tract Symptoms
GUIDELINES ON MALE LOWER
URINARY TRACT SYMPTOMS (LUTS),
INCLUDING BENIGN PROSTATIC
OBSTRUCTION (BPO)
(Text update February 2012)
M. Oelke (chair), A. Bachmann, A. Descazeaud, M. Emberton,
S. Gravas, M.C. Michel, J. NDow, J. Nordling, J.J. de la Rosette
The EAU Guideline on Male LUTS is a symptom-orientated
guideline that mainly reviews LUTS secondary to benign
prostatic enlargement (BPE) or benign prostatic obstruction
(BPO), detrusor overactivity or overactive bladder, and noc-
turia due to nocturnal polyuria in men aged 40 years or older.
The multifactorial aetiology of LUTS is illustrated in Figure 1.
An update of these guidelines will be presented in the course
of 2013.
Assessment
Systematic diagnostic work-up is recommended (Figure 2).
History, symptom and quality-of-life questionnaire, physical
examination, urinalysis, blood analysis, ultrasonography (US)
of the prostate, bladder and kidneys, as well as uroflowmetry
and measurement of post-void residual urine are recom-
mended in all patients. Optional tests are bladder diary in men
with urinary frequency or nocturia; computer-urodynamic
evaluation before surgical treatment should be performed in
men who:
cannot void 150 ml;
have a maximum flow rate 15 mL/s;
are < 50 or > 80 years of age;
can void but have post-void residual urine > 300 mL;
108 Male Lower Urinary Tract Symptoms
are suspicious of having neurogenic bladder dysfunction;
have bilateral hydronephrosis;
had radical pelvic surgery or;
had previous unsuccessful (invasive) treatment.
Note that only the diagnosis of nocturnal polyuria (> 33% of
the 24-hour urine excretion over night) can be made by the
bladder diary, whereas the diagnosis of all other forms of non-
neurogenic benign forms of LUTS in men aged 40 years or
older is mainly made by exclusion.
Benign
Prostatic
Obstruction
(BPO)
OAB -
detrusor
overactivity
Nocturnal
polyuria
Detrusor
underactivity
Neurogenic
bladder
dysfunction
Urinary
tract
infection
Foreign
body
LUTS
Prostatitis
Urethral
stricture
Bladder
tumour
Distal
ureteral
stone
And others
...
Figure 1: Causes of male lower urinary tract symptoms (LUTS)
109 Male Lower Urinary Tract Symptoms



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Figure 2: Assessment algorithm of LUTS in men aged 40 years
or older
Treatment
The level of evidence and the grade of recommendation
(according to the Oxford Centre for Evidence-Based Medicine
110 Male Lower Urinary Tract Symptoms
[CEBM]) for each treatment option are summarised in Table 1.
Conservative treatment
Watchful waiting (WW) is suitable for mild-to-moderate
uncomplicated LUTS. It includes education, re-assurance, life-
style advice, and periodic monitoring.
Drug treatment
Drugs used for the treatment of various forms of male LUTS
are listed in Table 2.
Table 2: Key pharmacokinetic properties and standard
doses of drugs licensed in Europe for the treatment
of LUTS
Drug (class) t
max

[hours]
t [hours] Recommended
daily dose

1
-adrenoceptor antagonists (for treating symptoms of
BPH)
Alfuzosin IR 1.5 4-6 3 x 2.5 mg
Alfuzosin SR 3 8 2 x 5 mg
Alfuzosin XL 9 11 1 x 10 mg
Doxazosin IR 2-3 20 1 x 2-8 mg
Doxazosin GITS 8-12 20 1 x 4-8 mg
Silodosin 2.5 11-18 1 x 4-8 mg
Tamsulosin MR 6 10-13 1 x 0.4 mg
Tamsulosin
OCAS
4-6 14-15 1 x 0.4 mg
Terazosin 1-2 8-14 1 x 5-10 mg
5-reductase inhibitors (for treating benign prostatic
enlargement due to BPH)
Dutasteride 1-3 3-5 weeks 1 x 0.5 mg
Finasteride 2 6-8 1 x 5 mg
111 Male Lower Urinary Tract Symptoms
Antimuscarinic drugs (for treating OAB/storage symptoms)
Darifenacin 7 13 - 19 1 x 7.5-15 mg
Fesoterodine 5 7 1 x 4-8 mg
Oxybutynin IR 0.5 - 1 2 - 4 3-4 x 2.5-5 mg
Oxybutynin ER 5 16 2-3 x 5 mg
Propiverine 2.5 13 - 20 2-3 x 15 mg
Propiverine ER 7 20 1 x 30 mg
Solifenacin 4 - 6 45 - 68 1 x 5-10 mg
Tolterodine IR 1 - 3 2-10 2 x 1-2 mg
Tolterodine ER 4 6 - 10 1 x 4 mg
Trospium chlo-
ride
4 - 6 5 - 15 3 x 10-15 mg or 2
x 10-20 mg
Antidiuretic (for treating nocturnal polyuria)
Desmopressin 1-2 3 1 x 0.1-0.4 mg
orally before
sleeping
Phosphodiesterase 5 Inhibitors (for treating erectile
dysfunction male LUTS [experimental])
Sildenafil 1 (0.5-2) * 3-5 1 x 25-100 mg
Tadalafil 2 (0.5-12) 17.5 1 x 2.5-20 mg
Vardenafil 1 (0.5-2) * 4-5 2 x 10 mg
ER = extended release; GITS = gastrointestinal therapeutic
system; IR = immediate release; MR = modified release; OCAS
= oral controlled absorption system; SR = sustained release;
t
max
= time to maximum plasma concentration; t = elimina-
tion half-life. *dependent on food intake (i.e. slower resorption
of the drug and an increase in t
max
by approximately 1 hour
after a fatty meal).

1
-adrenoceptor antagonists (
1
-blockers) are often the
first-line drug treatment of male LUTS because of their rapid
onset of action and good efficacy. They are also used inter-
mittently in LUTS of fluctuating symptom intensity. The main
112 Male Lower Urinary Tract Symptoms

1
-blockers are alfuzosin, doxazosin, tamsulosin and tera-
zosin. All
1
-blockers have a similar efficacy in mild, moderate,
or severe LUTS and in different age groups. Efficacy may be
better with smaller prostates (< 40 mL). Some patients still
require surgical treatment because
1
-blockers do not reduce
prostate size or prevent acute urinary retention.
1
-blocker
efficacy is maintained over at least 4 years. The commonest
side effects of
1
-blockers are asthenia, dizziness and (orthos-
tatic) hypotension.
5-reductase inhibitors should only be considered in men
with bothersome moderate-to-severe LUTS and enlarged
prostates (prostate volume > 40 mL) or elevated PSA con-
centration (> 1.4-1.6 g/L). 5-reductase inhibitors are only
suitable for long-term treatment (over many years) because
of their slow onset of action. Dutasteride and finasteride are
equally effective. Symptom reduction may not be better than
placebo in patients with prostates < 40 mL. 5-reductase
inhibitors reduce LUTS more slowly than
1
-blockers and, in
finasteride, less effectively. The greater the baseline pros-
tate volume (or serum PSA concentration), the faster and
more pronounced the symptomatic benefit of dutasteride.
5-reductase inhibitors, but not
1
-blockers, reduce the
long-term (> 1 year) risk of acute urinary retention or need for
surgery. The most relevant side effects include reduced libido,
erectile dysfunction and ejaculation disorders. About 1-2% of
patients develop gynaecomastia (breast enlargement with
breast or nipple tenderness).
Muscarinic receptor antagonists may benefit men with small-
er PSA levels (smaller prostates). Tolterodine significantly
reduced urgency incontinence, daytime or 24-hour frequency,
and urgency-related voiding compared to placebo. Nocturia,
urgency and the International Prostate Symptom Score (IPSS)
were also reduced, though without statistical significance.
113 Male Lower Urinary Tract Symptoms
Although studies have been carried out with tolterodine or
fesoterodine, other antimuscarinic agents are likely to show
similar effects. Muscarinic receptor antagonists are generally
well tolerated. Adverse effects include dry mouth, constipa-
tion, micturition difficulties, nasopharyngitis and dizziness.
An increase in post-void residual (PVR) urine in men without
BPO is minimal. Antimuscarinic drugs are not recommended
in men with BPO because of a theoretical decrease in blad-
der strength, which might be associated with PVR or urinary
retention. However, short-term treatment with antimuscarinic
drugs in men with BPO is safe. There are no published long-
term studies addressing efficacy. On this basis, antimuscari-
nic drugs, especially in men with BPO, should be prescribed
with caution, and regular re-evaluations of IPSS and PVR are
advised.
Plant extracts (phytotherapy): no specific recommendations
can be made about phytotherapy in male LUTS because of
product heterogeneity, lack of regulatory framework, and
research methodological problems.
Desmopressin is a synthetic analogue of the antidiuretic
hormone, arginine vasopressin, which plays a key role in body
water homoeostasis and urine production. Desmopressin
is used to treat nocturia due to nocturnal polyuria in adults.
The clinical effects (urine volume decrease, increase in urine
osmolality) last about 8-12 hours. The most frequent adverse
events are headache, nausea, diarrhoea, abdominal pain,
dizziness, dry mouth, and hyponatremia (serum sodium con-
centration <130 mmol/L). Peripheral oedema and hyperten-
sion were reported with long-term treatment. Serum sodium
concentration should be monitored regularly to detect
hyponatremia. The risk of hyponatremia increases with age,
lower serum sodium concentration at baseline, and higher
basal 24-hour urine volume per bodyweight.
114 Male Lower Urinary Tract Symptoms
Combination therapies

1
-blocker + 5-reductase inhibitor are best prescribed long
term (> 12 months) to men with moderate-to-severe LUTS
at risk of disease progression (e.g. higher prostate volume,
higher PSA concentration, advanced age). Combination
treatment is better than monotherapy at reducing symptoms
and improving Q
max
, and better than
1
-blockers at reducing
the risk of acute urinary retention and the need for surgery.
The
1
-blocker may be discontinued after 6 months in men
with moderate LUTS at baseline, but longer-term combina-
tion therapy is beneficial in severe LUTS (IPSS > 20). Adverse
events of both drug classes have been reported.

1
-blocker + muscarinic receptor antagonist are more effica-
cious in reducing voiding frequency, nocturia, or IPSS than

1
-blockers or placebo alone. Furthermore, combination
treatment significantly reduced urgency urinary incontinence
episodes and urgency and increased quality of life. Persistent
LUTS during
1
-blocker treatment can be reduced by the
addition of a muscarinic receptor antagonist (tolterodine)
especially if there is detrusor overactivity. Adverse events of
both drug classes are reported. PVR measurement is recom-
mended during combination treatment to assess increased
PVR or urinary retention.
Phosphodiesterase 5 inhibitors (PDE5Is) are still experimen-
tal and should not be used routinely.
Summary conservative and/or medical treatment
Behavioural with or without medical treatments are usually
the first choice of therapy. A flowchart illustrating conserva-
tive and medical treatment choices according to evidence-
based medicine and patients profiles is provided in Figure 3.
115 Male Lower Urinary Tract Symptoms
Figure 3: Treatment algorithm of male LUTS using medical
and/or conservative treatment options. Treatment
decisions depend on results assessed during initial
evaluation ().The absence (-) or presence of the
condition (+) are indicated in circles (o).
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116 Male Lower Urinary Tract Symptoms
Surgical treatment
Prostate surgery is usually required when patients have
experienced recurrent or refractory urinary retention, over-
flow incontinence, recurrent urinary tract infections, bladder
stones or diverticula, treatment-resistant macroscopic hae-
maturia due to BPH/BPE, or dilatation of the upper urinary
tract due to BPO, with or without renal insufficiency (absolute
operation indications, need for surgery). Additionally, surgery
is usually needed when patients have had insufficient relief in
LUTS or PVR after conservative or medical treatments (rela-
tive operation indications).
Transurethral Resection (TURP) or Transurethral Incision
of the Prostate (TUIP): TUIP reduces BPO by splitting the
bladder outlet without tissue removal and TURP removes
tissue from the prostatic transition zone to reduce BPO and,
secondly LUTS. The choice between TURP and TUIP is based
on prostate volume with prostates < 30 mL suitable for TUIP
and prostates of 30-80 mL for TURP. Urinary tract infections
should be treated prior to surgery. Bipolar TURP is an alterna-
tive to monopolar TURP in moderate-to-severe LUTS second-
ary to BPO. It has similar efficacy but lower morbidity.
Open prostatectomy is the oldest surgical treatment moda-
lity for moderate-to-severe LUTS secondary to BPO. Removal
of prostatic tissue resolves BPO and, secondarily, LUTS.
Efficacy is maintained > 5 years. Perioperative complications
include mortality and blood transfusion. Long-term complica-
tions are urinary incontinence and bladder neck stenosis or
urethral stricture. Open prostatectomy is the most invasive,
but also the most effective and durable procedure for treat-
ing LUTS/BPO. Only Holmium enucleation (HoLEP) delivers
similar results, but with less morbidity. In the absence of a
Holmium laser, open prostatectomy is the surgical treatment
of choice for men with prostates > 80 mL.
117 Male Lower Urinary Tract Symptoms
Transurethral Microwave Therapy (TUMT) emits microwave
radiation through an intra-urethral antenna to deliver heat
into the prostate, which leads to tissue destruction, apopto-
sis, and denervation of -receptors reducing BPO and LUTS.
Treatment is well tolerated, although most patients experi-
ence perineal discomfort and urinary urgency and require pain
medication prior to or during therapy. TUMT is an outpatient
procedure and an alternative for older patients with co-mor-
bidities and those at risk for anaesthesia or otherwise unsuit-
able for invasive treatment. Baseline parameters predicting
an unfavourable outcome include small prostates, mild-to-
moderate BOO, and low energy delivered during treatment.
Transurethral Needle Ablation (TUNA) of the prostate
delivers low-level radiofrequency energy to the prostate via
needles inserted transurethrally into the prostatic parenchy-
ma. The energy induces coagulation necroses in the prostatic
transition zone resulting in prostate volume reduction and
resolution of BPO. TUNA is unsuitable for prostates > 75 mL
or isolated bladder neck obstruction. TUNA can be per-
formed as a day-case procedure and is associated with fewer
side effects than TURP (e.g. bleeding, erectile dysfunction,
urinary incontinence).
Holmium Laser Enucleation (HoLEP) or Holmium Laser
Resection of the Prostate (HoLRP): the holmium:yttrium-alu-
minum-garnet (Ho:YAG) laser with a wavelength of 2140 nm is
a pulsed, solid-state laser. Resection is usually performed in
prostates < 60 mL, while enucleation is used for larger glands.
Patients using anticoagulant medication and those with uri-
nary retention can be treated safely. Dysuria is the most com-
mon peri-operative complication.
Laser vaporisation of prostate (KTP, Greenlight) leads to
immediate removal of prostatic tissue, relief of BPO and,
118 Male Lower Urinary Tract Symptoms
secondarily, reduction of LUTS. Because no tissue for patho-
logical examination can be harvested, screening for prostate
cancer, if indicated, should be carried out before the laser
operation. The treatment choice of tissue ablation depends
on the availability of the armamentarium, patients choice,
concomitant morbidity or drug use, and experience of the
surgeon.
Prostate stents are an alternative to catheterisation for
men unfit for surgery. Stents require a functioning detrusor.
Insertion is usually performed in an outpatient setting under
local anaesthesia. Placement is confirmed by abdominal US
or cystoscopy. Antibiotic prophylaxis is only necessary with a
positive urine culture.
Ethanol or botulinum toxin injections into the prostate are
still experimental.
Summary surgical treatment
The choice of the surgical technique depends primarily on
prostate size, co-morbidities of the patient, and the ability to
have anaesthesia but also on patients preferences, willing-
ness to accept surgery-associated side effects, availability of
the surgical armamentarium, and experience of the surgeon
with these operation techniques. A flowchart illustrating
surgical treatment choices according to patients profiles is
provided in Figure 4.
119 Male Lower Urinary Tract Symptoms
Figure 4: Treatment algorithm of bothersome LUTS refractory
to conservative/medical treatment or in cases of
absolute operation indications. The flowchart was
stratified by the patients ability to have anaesthe-
sia, cardiovascular risk, and prostate size.
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120 Male Lower Urinary Tract Symptoms
Follow-up
The below listed follow-up strategy is recommended:
Patients with WW should be reviewed at 6 months and
then annually, provided symptoms do not deteriorate or
absolute indications develop for surgical treatment.
Patients receiving
1
-blockers, muscarinic receptor antag-
onists, or a combination of
1
-blockers + 5-reductase
inhibitors or muscarinic receptor antagonists should be
reviewed 4-6 weeks after drug initiation. If patients gain
symptomatic relief in the absence of troublesome adverse
events, drug therapy may be continued. Patients should be
reviewed at 6 months and then annually, provided symp-
toms do not deteriorate or absolute indications develop
for surgical treatment.
Patients receiving 5-reductase inhibitor monotherapy
should be reviewed after 12 weeks and 6 months to deter-
mine their response and adverse events.
In patients receiving desmopressin, serum sodium concen-
tration should be measured at day 3 and 7 as well as after
1 month and, if serum sodium concentration has remained
normal, every 3 months subsequently; the follow-up
sequence should be re-started after dose escalation.
Patients after prostate surgery should be reviewed 4-6
weeks after catheter removal to evaluate treatment
response and adverse events. If patients have sympto-
matic relief and are without adverse events further re-
assessment is not necessary.
121 Male Lower Urinary Tract Symptoms
Table 1: Level of Evidence (LE) and Grade of
Recommendation (GR) of various treatments of male LUTS
and follow-up
LE GR
Conservative treatment Watchful Waiting
Suitable for men with mild symptoms. 1b A
Men with LUTS should be offered lifestyle
advice prior to or concurrent with treat-
ment.
1b A
Drug treatment
1.
1
-blockers should be offered to men with
moderate-to-severe LUTS.
1a A
2. 5-reductase inhibitors should be offered
to men who have moderate-to-severe
LUTS and an enlarged prostate (> 40
mL). 5-reductase inhibitors can prevent
disease progression with regard to acute
urinary retention and need for surgery.
1b A
3. Muscarinic receptor antagonists might
be considered in men with moderate-to-
severe LUTS who have predominantly
bladder storage symptoms.
Caution is advised in men with bladder
outlet obstruction (BOO).
1b
4
B
C
4. Desmopressin can be used for the treat-
ment of nocturia due to nocturnal polyu-
ria.
1b A
122 Male Lower Urinary Tract Symptoms
5. Combination treatment with an

1
-blocker together with a 5-reductase
inhibitor should be offered to men with
bothersome moderate-to-severe LUTS,
enlarged prostates, and reduced Q
max

(men likely to develop disease progres-
sion).
Combination treatment is not recom-
mended for short-term therapy (< 1 year).
1b A
6. Combination treatment with an

1
-blocker together with a muscarinic
receptor antagonists might be consid-
ered in patients with bothersome moder-
ate-to-severe LUTS if symptom relief has
been insufficient with the monotherapy
of either drug. Combination treatment
should cautiously be prescribed in men
with suspected BOO.
1b
2b
B
B
7. PDE5Is reduce moderate-to-severe male
LUTS but are experimental and restricted
to men with erectile dysfunction, pulmo-
nary arterial hypertension, or to those
who have bothersome LUTS in clinical
trials.
1b A
Surgical treatment
1. Monopolar TURP is the current surgical
standard procedure for men with pros-
tate sizes of 30-80 mL and bothersome
moderate-to-severe LUTS secondary of
BPO. Monopolar TURP provides subjec-
tive and objective improvement rates
superior to medical or minimally invasive
treatments.
1a A
Bipolar TURP achieves short-term results
comparable to monopolar TURP.
1a A
123 Male Lower Urinary Tract Symptoms
TUIP is the surgical therapy of choice for
men with prostate sizes < 30 mL, without
a middle lobe, and bothersome moderate-
to-severe LUTS secondary to BPO.
1a A
2. Open prostatectomy is the first choice of
surgical treatment in men with prostate
sizes > 80 mL, bothersome moderate-to-
severe LUTS secondary to BPO, and LUTS
refractory to drugs in the absence of a
Holmium laser.
1b A
Open prostatectomy is the most invasive
surgical method with significant morbid-
ity.
1b A
3. TUMT achieves symptom improvement
comparable to TURP, but is associated
with decreased morbidity and lower flow
improvements.
1a A
Durability is in favour of TURP with lower
re-treatment rates compared to TUMT.
1a A
4. TUNA is an alternative to TURP for
patients who wish to defer/avoid (com-
plications of) TURP, but patients should
be aware of significant re-treatment rates
and less improvement in symptoms and
quality of life.
1a A
5. HoLEP and 532 nm laser vaporisation of
the prostate are minimally invasive alter-
natives to TURP in men with moderate-
to-severe LUTS due to BPO. Laser opera-
tions lead to immediate, objective and
subjective improvements comparable to
TURP.
1b A
124 Male Lower Urinary Tract Symptoms
With regard to intra-operative safety, 532
nm laser vaporisation is superior to TURP
and should be considered in patients
receiving anticoagulant medication or
with high cardiovascular risk.
3 B
With regard to long-term complication
rates, results are only available for HoLEP
and are comparable to TURP.
1b A
6. Prostatic stents are an alternative to
catheterisation for men unfit for surgery.
Stents may have a role in the temporary
relief of LUTS/BPO after minimally inva-
sive treatment.
3 C
7. Intra-prostatic ethanol injections for men
with moderate-to-severe LUTS secondary
to BPO are still experimental and should
be performed only in clinical trials.
3 C
8. Intra-prostatic BTX injections for men
with bothersome moderate-to-severe
LUTS secondary to BPO or men in uri-
nary retention are still experimental and
should be performed only in clinical trials.
3 C
Follow-up
1. Follow-up for all conservative, medical or
operative treatment modalities is based
on empirical data or theoretical consider-
ations but not on evidence based studies.
3-4 C
This short booklet text is based on the more comprehensive EAU
guidelines (ISBN 978-90-79754-83-0), available to all members of the
European Association of Urology at their website,
http://www.uroweb.org.
125 Male Sexual Dysfunction
GUIDELINES ON MALE SEXUAL
DYSFUNCTION: Erectile Dysfunction
and Premature Ejaculation
(Text update March 2013)
E. Wespes (chair), I. Eardley, F. Giuliano, D. Hatzichristou,
K. Hatzimouratidis (vice-chair), I. Moncada, A. Salonia, Y. Vardi
Eur Urol 2006 May;49(5):806-15
Eur Urol 2010 May;57(5):804-14
Eur Urol 2012 Sep;62(3):543-52
ERECTILE DYSFUNCTION
Definition, epidemiology and risk factors
Erectile dysfunction (ED) is the persistent inability to attain
and maintain an erection sufficient to permit satisfactory sex-
ual performance. Although ED is a benign disorder, it affects
physical and psychosocial health and has a significant impact
on the quality of life (QoL) of sufferers and their partners.
There is increasing evidence that ED can be an early mani-
festation of coronary artery and peripheral vascular disease;
thus, ED should not be regarded only as a QoL issue but also
as a potential warning sign of cardiovascular disease includ-
ing lack of exercise, obesity, smoking, hypercholesterolaemia,
and the metabolic syndrome. The risk of ED may be reduced
by modifying these risk factors, particularly taking exercise or
losing weight. Another risk factor for ED is radical prostatec-
tomy (RP) in any form (open, laparoscopic, or robotic) because
of the risk of cavernosal nerve injury, poor oxygenation of the
corpora cavernosa, and vascular insufficiency.
126 Male Sexual Dysfunction
Diagnosis and work-up
Basic work-up
The basic work-up (minimal diagnostic evaluation) outlined in
Fig. 1 must be performed in every patient with ED.
Due to the potential cardiac risks associated with sexual
activity, the three Princeton Consensus Conference stratified
patients with ED wanting to initiate, or resume, sexual activity
into three risk categories. The low-risk group includes asymp-
tomatic patients with less than three risk factors for coronary
artery disease (excluding male gender), mild or stable angina
(evaluated and/or being treated), uncomplicated past myocar-
dial infarction, left ventricular dysfunction or congestive heart
failure (NYHA class I), post-successful coronary revascularisa-
tion, controlled hypertension, and mild valvular disease. All
other patients are included in an intermediate- or high-risk
category and require a cardiology consultation.
Specific examinations and tests
Although most patients with ED can be managed within the
sexual care setting, some circumstances require specific diag-
nostic testing:
Patients with primary erectile disorder (not caused by
organic disease or psychogenic disorder).
Young patients with a history of pelvic or perineal trauma
who could benefit from potentially curative vascular sur-
gery.
Patients with penile deformities (e.g. Peyronies disease,
congenital curvature) that might require surgical correc-
tion.
Patients with complex psychiatric or psychosexual disor-
ders.
Patients with complex endocrine disorders.
Specific tests may also be indicated at the request of the
patient or his partner.
127 Male Sexual Dysfunction
For medico-legal reasons (e.g. penile prosthesis implant,
sexual abuse).
Specific diagnostic tests include:
nocturnal penile tumescence and rigidity (NTPR) using
Rigiscan;
vascular studies:
- intracavernous vasoactive drug injection;
- duplex ultrasound of the cavernous arteries;
- dynamic infusion cavernosometry/cavernosography
(DICC);
- internal pudendal arteriography;
neurological studies (e.g. bulbocavernosus reflex latency,
nerve conduction studies);
endocrinological studies;
specialised psychodiagnostic evaluation.
The NPTR should take place for at least two nights. A func-
tional erectile mechanism is indicated by an erectile event of
at least 60% rigidity recorded on the tip of the penis, lasting
for 10 min or longer.
The intracavernous injection test provides limited information
about vascular status. However, Duplex ultrasound provides
a simple way of assessing vascular status. Further vascular
investigation is unnecessary if Duplex ultrasound is normal,
as indicated by a peak systolic blood flow > 30 cm/s an end-
diastolic velocity of < 3 cm/s and a resistance index > 0.8. If
ultrasound is abnormal, however, arteriography and DICC
should be performed only in patients who are potential candi-
dates for vascular reconstructive surgery.
128 Male Sexual Dysfunction
Recommendations for the diagnostic work-up LE GR
Clinical use of a validated questionnaire related
to ED may help assess all sexual function
domains and the effect of a specific treatment
modality.
3 B
Physical examination is needed in the initial
assessment of ED to identify underlying medical
conditions associated with ED.
4 B
Routine laboratory tests, including glucose-lipid
profile and total testosterone, are required to
identify and treat any reversible risk factors and
modifiable lifestyle factors.
4 B
Specific diagnostic tests are indicated by only a
few conditions.
4 B
ED = erectile dysfunction.
Treatment of ED
As a rule, EC can be treated successfully with current treat-
ment options, but cannot be cured, with the exception of:
Psychogenic ED: psychosexual therapy may be given,
either alone or with another therapeutic approach, but
takes time and has had variable results.
Post-traumatic arteriogenic ED in young patients: surgical
penile revascularisation has a 60-70% long-term success
rate.
Hormonal causes of ED: testosterone replacement therapy
is effective, but should only be used after other endocrino-
logical causes for testicular failure have been excluded.
Currently, it is contraindicated in men with untreated
prostate cancer, unstable cardiac disease and severe LUT
obstruction. Close follow-up is necessary, including digital
rectal examination (DRE), serum prostate-specific antigen
(PSA) and haematocrit assessment, as well as monitoring
the development of hepatic or prostatic disease.
129 Male Sexual Dysfunction
Fig. 1: Minimal diagnostic evaluation (basic work-up) in
patients with ED
Patient with ED (self-reported)
Identify
common
causes of
ED
Identify
reversible
risk factors
for ED
Assess psy-
chosocial
status
Medical and psychosexual history
(use of validated instruments, e.g. IIEF)
Identify
sexual
problems
other than
ED
Prostatic
disease
Signs of
hypogonad-
ism
Cardio-
vascular and
neuro-
logical status

Focused physical examination
Penile
deformities
Total testosterone
(morning sample).
If indicated, bio-available of
free testosterone



Laboratory tests
Glucose-lipid prole
(if not assessed in the
last 12 months)

IIEF = International Index for Erectile Function; ED = erectile
dysfunction.
130 Male Sexual Dysfunction
The use of pro-erectile drugs following RP is very important
in achieving erectile function after surgery. Rehabilitation
should start as soon as possible following RP.
Most men with ED will be treated with treatment options that
are not cause-specific. This approach requires a structured
treatment strategy that depends on efficacy, safety, invasive-
ness, and cost, as well as patient and partner satisfaction. A
treatment algorithm for ED is given in Fig. 2.
First-line therapy
Oral pharmacotherapy
Three potent, selective PDE5 inhibitors (PDE5Is) have been
approved by the European Medicines Agency (EMA) for
the treatment of ED. They are not initiators of erection and
require sexual stimulation for an erection to occur. Efficacy is
defined as rigidity sufficient for vaginal penetration.
Sildenafil (Viagra)
Sildenafil is effective after 30-60 min from administration.
A heavy, fatty meal may reduce or prolong absorption. It is
administered in 25, 50 and 100 mg doses. The recommended
starting dose is 50 mg and adapted according to patient
response and side-effects. Efficacy may be maintained for
up to 12 h. Efficacy rates (erections sufficient for successful
intercourse) are 56%, 77% and 84% of men taking 25, 50 and
100 mg of sildenafil, respectively. The efficacy of sildenafil
in almost every subgroup of patients with ED has been well
established.
Tadalafil (Cialis)
Tadalafil is effective from 30 min after administration but its
peak efficacy occurs after about 2 h. Efficacy is maintained
for up to 36 h and is not affected by food. It is administered
in 10 and 20 mg doses. The recommended starting dose is 10
131 Male Sexual Dysfunction
mg and is adapted according to patient response and side-
effects. Efficacy rates are 67% and 81% of men taking 10 mg
and 20 mg of tadalafil, respectively. Tadalafil also improves
erections in difficult-to-treat subgroups.
Vardenafil (Levitra)
Vardenafil is effective after 30 min from administration. A
fatty meal, > 57% in fat, reduces its effect. It is administered in
5, 10 and 20 mg doses. The recommended starting dose is 10
mg and adapted according to the response and side-effects.
In vitro, it is 10-fold more potent than sildenafil. However, this
does not necessarily mean greater clinical efficacy. Efficacy
rates are 66%, 76% and 80% of men taking 5 mg, 10 mg and 20
mg of vardenafil, respectively. Vardenafil also improves erec-
tions in difficult-to-treat subgroups.
Choice of, or preference for, different PDE5Is
The choice of a PDE5I depends on the frequency of inter-
course (occasional use or regular therapy, 3-4 times weekly)
and the patients personal experience of the agent. Patients
need to know whether a drug is short- or long-acting, possible
disadvantages, and how to use it.
On-demand or chronic use of PDE5Is
Although PDE5Is were introduced as on-demand treatment,
in 2008, tadalafil was also approved for continuous, everyday
use in 2.5 and 5 mg doses. Daily dosing was well tolerated and
significantly improved erectile function. Similar results have
been found in diabetic patients. Daily tadalafil provides an
alternative to on-demand dosing for couples that prefer spon-
taneous rather than scheduled sexual activity or who have
frequent sexual activity.
Adverse events
Common adverse events include headache, flushing, dizzi-
132 Male Sexual Dysfunction
ness, dyspepsia, and nasal congestion. Sildenafil and vardena-
fil have been associated with visual abnormalities in less than
2% of patients, while tadalafil has been associated with back
pain/myalgia in 6% of patients. However, adverse events are
generally mild in nature, self-limited by continuous use, and
the dropout rate due to adverse events is similar to placebo.
Cardiovascular safety
Clinical trials and post-marketing data of all PDE5Is have
demonstrated no increase in myocardial infarction rates. No
PDE5I has adversely affected total exercise time or time to
ischaemia during exercise testing in men with stable angina.
In fact, they may improve exercise tests.
Nitrates are totally contraindicated with all PDE5Is due
to unpredictable hypotension. The duration of interaction
between organic nitrates and PDE5Is varies according to the
PDE5I and nitrate. If a patient develops angina while using a
PDE5I, other antiangina agents may be used instead of nitro-
glycerine or until after the appropriate time has passed (24 h
for sildenafil or vardenafil and 48 h for tadalafil).
In general, the adverse event profile of the PDE5I is not wors-
ened, even when the patient is on multiple antihypertensive
agents.
Alpha-blocker interactions
All PDE5Is appear to interact with alpha-blockers, which
under some conditions may result in orthostatic hypotension.
Patients should be stable on alpha-blocker therapy prior
to initiating combined treatment, and that the lowest dose
should be started initially of PDE5Is.
Dosage adjustments
Lower doses of PDE5Is may be required in patients taking
133 Male Sexual Dysfunction
ketoconazole, itraconazole, erythromycin, clarithromycin, and
HIV protease inhibitors (ritonavir, saquinavir). Higher doses of
PDE5Is may be necessary in patients taking rifampicin, phe-
nobarbital, phenytoin, or carbamazepine. Kidney or hepatic
dysfunction may require dose adjustments. In patients with
hypogonadism, androgen supplementation improves erectile
response.
Management of non-responders to PDE5Is
Physicians should check that the patient is using a licensed
medication and that the medication has been properly pre-
scribed and correctly used (adequate sexual stimulation,
dosage, and enough time between taking the medication and
attempt at intercourse).
Provided a patient is using a PDE5I appropriately, there are
several ways of improving efficacy. They include modification
of associated risk factors, treatment of associated hypogo-
nadism, changing to another PDE5I, or continuous use of a
PDE5I.
Vacuum erection devices
A vacuum erection device (VED) applies a negative pressure
to the penis to draw venous blood into the penis, which is
then retained by application of a visible constricting band at
the base of the penis. Efficacy, defined by an erection satis-
factory for intercourse, is as high as 90%. Satisfaction rates
range between 27% and 94%. Adverse events include penile
pain, numbness, and delayed ejaculation and occur in less
than 30% of patients. VED is acceptable for couples in a
stable relationship.
134 Male Sexual Dysfunction
Second-line therapy
Patients not responding to oral drugs may be offered intrac-
avernous injections. Alprostadil (Caverject, Edex/Viridal) is
the only drug approved for intracavernous treatment of ED.
It is the most efficacious monotherapy for intracavernous
treatment using 5-40 g doses. The patient should been rolled
in an office-based training programme (one or two visits) to
learn the correct injection process.
Complications of intracavernosal prostadil include penile pain
(50% of patients), prolonged erections (5%), priapism (1%),
and fibrosis (2%). Drug combinations (mainly the three-drug
combination of alprostadil + papaverine + phentolamine) may
increase efficacy by up to 90%. Fibrosis was found to be more
common (5-10%) if papaverine was used (depending on total
dose).
After 4 h of erection, patients are advised to consult their
doctor to avoid any damage to the intracavernous muscle, as
this will result in permanent impotence. Blood aspiration and
injection of phenylephrine are used to treat prolonged erec-
tions. If this problem occurs, the dosage of the next intracav-
ernosal injection is usually reduced.
Prostaglandin E1 may be administered intra-urethrally as a
semi-solid pellet (125-1000 g). A band placed at the base of
the penis improves the resulting rigidity. The clinical success
rate is lower than with intracavernosal injections, but about
70% of patients are satisfied with treatment. Side-effects
include local pain (29-41%), dizziness (1.9-14%), and urethral
bleeding (5%).
Third-line therapy (penile prostheses)
Surgical implantation of a penile prosthesis may be consid-
ered in patients who fail pharmacotherapy or who want a
135 Male Sexual Dysfunction
permanent solution. Prostheses are either malleable (semi
rigid) or inflatable (two- or three-piece). Most patients prefer
the three-piece inflatable devices because erections are
more natural, but these implants are much more expensive.
Satisfaction rates of 70-87% are reported from patients after
appropriate consultation.
Complications include mechanical failures and infections.
With antibiotic prophylaxis, the infection rate is 2-3% and
may be further reduced by using an antibiotic-impregnated or
hydrophilic-coated implant. Infection requires removing the
prosthesis, antibiotic administration and re-implantation after
6-12 months.
Recommendations for ED treatment LE GR
Lifestyle changes and risk factor modification
must precede or accompany ED treatment.
1a A
Pro-erectile treatments have to be given at the
earliest opportunity after radical prostatectomy.
1b A
When a curable cause of ED is found, it must be
treated first.
1b B
PDE5Is are first-line therapy. 1a A
Daily administration of PDE5Is may improve
results and restore erectile function.
1b A
A vacuum erection device can be used in
patients with stable relationship.
4 C
Intracavernous injection is second-line therapy. 1b B
Penile implant is third-line therapy. 4 C
PDE5I = phosphodiesterase type 5 inhibitor.
136 Male Sexual Dysfunction
Fig. 2: Treatment algorithm for ED
PDE5 inhibitor = phosphodiesterase type 5 inhibitor.
Assess therapeutic outcome:
Erectile response
Side-effects
Satisfaction with treatment
Consider penile prosthesis implantation
Inadequate treatment outcome
Treatment of erectile dysfunction (ED)
PDE5Is
Intracavernous injections
Vacuum devices
Intraurethral alprostadil
Identify and treat
curable causes of
ED
Lifestyle changes
and risk factor
modification
Provide education
and counselling to
patients and partners
Assess adequate use of treatment options
Provide new instructions and counselling
Re-trial
Consider alternative or combination therapy
Inadequate treatment outcome
Identify patient needs and expectations
Shared decision-making
Offer conjoint psychosocial and medical treatment
137 Male Sexual Dysfunction
PREMATURE EJACULATION
Definition, epidemiology and risk factors
The International Society for Sexual Medicine (ISSM) has
adopted a completely new definition of lifelong PE, which is
the first evidence-based definition: Premature ejaculation is
a male sexual dysfunction characterized by ejaculation which
always or nearly always occurs prior to or within about one
minute of vaginal penetration; and inability to delay ejacula-
tion on all or nearly all vaginal penetrations; and negative
personal consequences, such as distress, bother, frustration
and/or the avoidance of sexual intimacy.
Thus, PE may be classified as lifelong (primary) or acquired
(secondary). Lifelong PE is characterised by onset from the
first sexual experience and remains a problem during life.
Acquired PE is characterised by a gradual or sudden onset
with ejaculation being normal before onset of the problem.
Time to ejaculation is short, but not usually as fast as in life-
long PE.
Premature ejaculation has a detrimental effect on self-confi-
dence and relationship with the partner. It may cause mental
distress, anxiety, embarrassment, and depression. However,
most men with PE do not seek help.
Diagnostic work-up
Diagnosis of PE is based on the patients medical and sexual
history. The history should classify PE as lifelong or acquired
and determine whether PE is situational (under specific cir-
cumstances or with a specific partner) or consistent. Special
attention should be given to the length of time of ejaculation,
degree of sexual stimulus, impact on sexual activity and QoL,
and drug use or abuse. It is also important to distinguish PE
from ED.
138 Male Sexual Dysfunction
Recommendations for diagnosis of PE LE GR
Diagnosis and classification of PE is based on
medical and sexual history.
It should be multidimensional and assess IELT,
perceived control, distress, and interpersonal
difficulty due to the ejaculatory dysfunction.
1a A
Clinical use of self-estimated IELT is adequate.
Stopwatch-measured IELT is necessary in clini-
cal trials.
2a B
Patient-reported outcomes have the potential
to identify men with PE. Further research is
needed before they can be recommended for
clinical use.
3 C
Physical examination may be necessary in initial
assessment of PE to identify underlying medical
conditions associated with PE or other sexual
dysfunctions particularly ED.
3 C
Routine laboratory or neurophysiological tests
are not recommended. Additional tests should
be directed by specific findings from history or
physical examination.
3 C
IELT = intravaginal ejaculatory latency time.
Treatment of PE
In many relationships, PE causes few, if any, problems. In
such cases, treatment should be limited to psychosexual
counselling. Before beginning treatment, it is essential to
discuss patient expectations thoroughly. Erectile dysfunction
or other sexual dysfunction or genitourinary infection (e.g.
prostatitis) should be treated first or at the same time as PE.
Various behavioural techniques have demonstrated benefit in
treating PE. In lifelong PE, behavioural techniques are not rec-
ommended for first-line treatment. They are time-intensive,
require the support of a partner, and can be difficult to do.
139 Male Sexual Dysfunction
Pharmacotherapy is the basis of treatment in lifelong PE but
all medical treatments are off-label indications. Only chronic
selective serotonin reuptake inhibitors (SSRIs) and on-
demand topical anaesthetic agents have consistently shown
efficacy in PE. A treatment algorithm for PE is presented in
Fig. 3.
Psychological/behavioural strategies
Behavioural strategies mainly include the stop-start pro-
gramme developed by Semans and its modification, the
squeeze technique, proposed by Masters and Johnson
(several modifications exist). Masturbation before anticipa-
tion of sexual intercourse is another technique used by many
younger men.
Overall, success rates of 50-60% have been reported short
term. Improvements achieved with these techniques are
generally not maintained long term.
Topical anaesthetic agents
Lidocaine-prilocaine cream (5%) is applied for 20-30 min prior
to intercourse. A condom is required to avoid diffusion of
the topical anaesthetic agent into the vaginal wall causing
numbness in the partner. In two RCTs, lidocaine-prilocaine
cream significantly increased the stopwatch-measured IELT
compared to placebo. No significant side-effects have been
reported. An aerosol formulation of lidocaine 7.5 mg plus
prilocaine 2.5 mg (Topical Eutectic Mixture for Premature
Ejaculation, TEMPE) is under evaluation and has shown simi-
lar results.
SS-cream is a topical anaesthetic agent made from the
extracts of nine herbs. It is applied to the glans penis 1 h
before and washed off immediately prior to coitus. In a RCT,
application of 0.2 g SS-cream significantly improved IELT
140 Male Sexual Dysfunction
and satisfaction compared to the placebo group. Mild local
burning and mild pain were reported by 18.5% of patients.
No adverse effects on sexual function or partner or systemic
side-effects were observed.
Selective serotonin reuptake inhibitors
Commonly used selective serotonin reuptake inhibitors
(SSRIs) include paroxetine (20-40 mg/day), sertraline (25-
200 mg/day), and fluoxetine (10-60 mg). Selective serotonin
reuptake inhibitors were expected to increase the geometric
mean IELT by 2.6-fold to 13.2-fold. Paroxetine was found
to be superior to fluoxetine, clomipramine, and sertraline.
Ejaculation delay may start a few days after drug intake, but
it is more evident after 1-2 weeks and may be maintained for
several years. Common side-effects of SSRIs include fatigue,
drowsiness, yawning, nausea, vomiting, dry mouth, diarrhoea,
and perspiration; they are usually mild and gradually improve
after 2-3 weeks. Decreased libido, anorgasmia, anejaculation,
and ED have been also reported. On-demand treatment is
inferior to daily dosing, but may be combined with an initial
trial of daily treatment or concomitant low-dose daily treat-
ment to reduce adverse effects.
Dapoxetine is a potent SSRI, which has been specially
designed as an on-demand oral treatment for PE. An inte-
grated analysis of two RCTs reported that dapoxetine, 30
and 60 mg, improved IELT significantly compared to placebo.
Improved ejaculation control was reported by 51% and 58%
of patients in the 30 mg and 60 mg dosage groups, respec-
tively. Both dapoxetine doses were effective on the first dose.
Common adverse events were nausea, diarrhoea, headache,
and dizziness. Dapoxetine has been approved (December
2008) for the on-demand treatment of PE in seven European
countries (Sweden, Austria, Finland, Germany, Spain, Italy, and
Portugal). This is currently the first and only drug approved for
141 Male Sexual Dysfunction
such an indication.
Phosphodiesterase type 5 inhibitors
Several recent studies have supported the therapeutic role of
PDE5Is in PE. However, there is only one RCT comparing silde-
nafil to placebo. Although IELT was not significantly improved,
sildenafil increased confidence, the perception of ejaculatory
control and overall sexual satisfaction, reduced anxiety, and
decreased the refractory time to achieve a second erection
after ejaculation.
Recommendations for PE treatment LE GR
Erectile dysfunction, other sexual dysfunction,
or genitourinary infection (e.g. prostatitis)
should be treated first.
2a B
Behavioural techniques can benefit PE.
However, they are time intensive, require the
support of a partner, and can be difficult to do.
3 C
Pharmacotherapy is the basis of treatment in
lifelong PE.
1a A
Daily SSRIs are first-line, off-label, pharmaco-
logical treatment for PE. The pharmacokinetic
profile of currently available SSRIs is not amena-
ble to on-demand dosing.
1a A
Dapoxetine, a short-acting SSRI, has already
been approved for the on-demand treatment of
PE in seven European countries.
1a A
Topical anaesthetic agents provide viable alter-
natives to SSRIs (off-label).
1b A
A trial of PDE5Is may be attempted. 2b C
Recurrence is likely after treatment cessation. 1b A
Behavioural therapy may augment pharmaco-
therapy to enhance prevention of relapse.
3 C
SSRI = selective serotonin reuptake inhibitor.
142 Male Sexual Dysfunction
Fig. 3: Management of PE
PE = premature ejaculation; IELT = intravaginal ejaculatory
latency time; ED = erectile dysfunction; SSRI = selective serot-
onin receptor inhibitor.
Adapted from Lue et al. Summary of the recommendations on
sexual dysfunctions in men. J Sex Med 2004;1:6-23.
Behavioural therapy includes stop/startechnique, squeeze sensate
focus
Pharmacotherapy (o label) includes SSRIs (daily use) and topical anaes-
thetics; it is recommended as rst-line treatment option in lifelong PE
Consider dapoxetine for on-demand use (the only approved drug for PE)
Atempt graduated withdrawal of Drug therapy afer 6-8 weeks
Pharmacotherapy
Relationship conselling
Behavioural therapy
Combination treatment
Behavioural therapy
Pharmacotherapy
Relationship counselling
Combination treatment
Lifelong PE Lifelong PE
Treatment of premature ejaculation
Patient counselling
Discussion of treatment options
If PE is secondary to ED, treat ED rst or concomitantly
Clinical diagnosis of premature ejaculation
based on patient/partner histor
Time to ejaculation (IELT)
Perceived degree of ejaculatory control
Degree of bother/distress
Onset and duration of PE
Psychosocial/Relationship issues
Medical history
143 Male Sexual Dysfunction
This short booklet text is based on the more comprehensive EAU
guidelines (ISBN 978-90-79754-71-7), available to all members of the
European Association of Urology at their website,
http://www.uroweb.org.
144 Penile Curvature
GUIDELINES ON
PENILE CURVATURE
E. Wespes (chair), K. Hatzimouratidis (vice-chair), I. Eardley,
F. Giuliano, D. Hatzichristou, I. Moncada, A. Salonia, Y. Vardi
Eur Urol 2012 Sep;62(3):543-52
Congenital penile curvature
Congenital penile curvature has an unknown cause and a
prevalence rate of 4-10% in the absence of urethral abnor-
malities. It is diagnosed from the medical and sexual history.
Physical examination during erection helps to document
curvature and exclude other pathologies. Erectile function is
normal, but can be compromised by excessive curvature.
Congenital penile curvature can only be treated surgically,
using the same principles as in Peyronies disease (see below),
except surgery can be performed at any time in adults.
Surgery is almost exclusively plication, resulting in high
curvature correction rates of 67-97%.
Peyronies disease
Epidemiology, physiopathology and natural history
The cause of Peyronies disease is unknown, but the most
widely accepted hypothesis is trauma to the tunica albuginea.
The most commonly associated comorbidities and risk factors
are diabetes, hypertension, lipid abnormalities, ischaemic car-
diopathy, erectile dysfunction, smoking and excessive alcohol
consumption. It has a prevalence rate of 0.4-9%. Dupuytrens
contracture is more common in Peyronies disease (9-39%),
while Peyronies disease occurs in 4% of patients with
Dupuytrens contracture. However, it is unclear if these fac-
tors contribute to the pathophysiology of Peyronies disease.
145 Penile Curvature
Two phases of the disease can be distinguished. The first is
the acute inflammatory phase, which may be associated with
pain. The second is the fibrotic phase, identified by formation
of hard palpable plaques that can be calcified, which results in
disease stabilisation. With time, penile curvature is expected
to worsen in 30-50% of patients or stabilise in 47-67% of
patients. Spontaneous improvement has been reported by
only 3-13% of patients and is more likely early in the disease.
Pain tends to resolve with time in 90% of men, usually during
the first 12 months after disease onset.
Patient evaluation
Particular attention should be given to whether the disease is
still active, as this will influence medical treatment or the
timing of surgery. Patients most likely to have active disease
are those with short symptom duration, pain during erec-
tion, or a recent change in penile curvature. Resolution of
pain and stability of the curvature for at least 3 months are
well-accepted criteria for disease stabilisation and referral for
surgical intervention.
A palpable node or plaque is usually identified on a routine
genitourinary assessment. However, there is no correlation
between plaque size and degree of curvature. The meas-
urement of length during erection is important because it
impacts directly on treatment decisions. An objective assess-
ment of penile curvature with an erection is mandatory. This
can be obtained by a home (self) photograph of a (preferably)
natural erection, a vacuum-assisted erection, or an intra-
cavernosal injection using vasoactive agents. Erectile dys-
function is common (> 50%) due to penile vascular disease.
The presence of erectile dysfunction may impact on treat-
ment strategy.
Ultrasound (US) measurement of the plaques size is inac-
146 Penile Curvature
curate and operator-dependent and is not recommended in
everyday clinical practice. Doppler US may be necessary to
assess vascular parameters.

Non-operative treatment
Conservative treatment of Peyronies disease is primarily
focused on patients in the early stages of disease. Several
options have been suggested, including oral pharmacother-
apy (vitamin E, potassium para-aminobenzoate, tamoxifen,
colchicine, acetyl esters of carnitine, pentoxifylline), intra-
lesional injection therapy (steroids, verapamil, clostridial col-
lagenase, interferon) and other topical treatments (verapamil,
iontophoresis, extracorporeal shock wave therapy, traction
devices, vacuum devices).
The role of conservative treatment in men with stable/chronic
disease has not yet been adequately defined. No single drug
has been approved by the European Medical Association for
the treatment of Peyronies disease.
The results of the studies on conservative treatment for
Peyronies disease are often contradictory because of several
methodological problems that make it difficult to provide
recommendations in everyday real life.
Recommendations on non-operative treatment
for Peyronies disease
LE GR
Conservative treatment for Peyronies disease
is primarily aimed at treating patients in
the early stages of disease. It is an option in
patients not fit for surgery or when surgery is
not acceptable to the patient.
3 C
147 Penile Curvature
Oral treatment with potassium para-aminoben-
zoate may result in a significant reduction
in penile plaque size and penile pain and an
increase in penile curvature stabilisation.
1b B
Intralesional treatment with verapamil may
result in a significant reduction in penile curva-
ture and plaque volume.
1b C
Intralesional treatment with clostridial
collagenase showed significant decreases in
the deviation angle, plaque width and plaque
length.
2b C
Intralesional treatment with interferon may
improve penile curvature, plaque size and
density, and pain.
1b B
Topical verapamil gel 15% may improve penile
curvature and plaque size.
1b B
Iontophoresis with verapamil 5 mg and
dexamethasone 8 mg may improve penile
curvature and plaque size.
1b B
Extracorporeal shock-wave treatment fails
to improve penile curvature and plaque size,
and should not be used to reduce plaque size.
However, it may help improve penile pain.
1b B
Penile traction devices and vacuum devices
may reduce penile deformity and increase
penile length.
3 C
Recommendations AGAINST
Intralesional treatment with steroids does not
reduce penile curvature, plaque size or penile
pain and is not recommended.
1b B
Oral treatment with vitamin E and tamoxifen is
not recommended.
2b B
Other oral treatments (acetyl esters of carni-
tine, pentoxifylline) are not recommended.
3 C
148 Penile Curvature
Surgical treatment
Although conservative treatment for Peyronies disease
should resolve painful erections in most men, only a small per-
centage experience any significant straightening of the penis.
The aim of surgery is to correct curvature and allow satisfac-
tory intercourse. Surgery is indicated only in patients with
stable disease for at least 3 months, although a 6-12 month
period has also been suggested.
Two major types of repair may be considered for both con-
genital penile curvature and Peyronies disease: penile short-
ening and penile lengthening procedures. Penile shortening
procedures include the Nesbit wedge resection and the plica-
tion techniques performed on the convex side of the penis.
Penile lengthening procedures are performed on the concave
side of the penis and require the use of a graft. They are used
to minimise penile shortening caused by Nesbit resection
or plication of the tunica albuginea or to correct complex
deformities. Several types of grafts include autologous grafts
(dermis, vein grafts, tunica albuginea, tunica vaginalis, tempo-
ralis fascia, buccal mucosa), allografts (cadaveric pericardium,
cadaveric fascia lata, cadaveric dura matter, cadaveric der-
mis), xenografts (porcine small intestine submucosa, bovine
pericardium, porcine dermis) and synthetic grafts (Gore-Tex,
Dacron). Finally, in patients with Peyronies disease and
erectile dysfunction not responding to medical treatments,
surgical correction of the curvature with concomitant penile
prosthesis implantation should be considered.
The decision on the most appropriate surgical procedure to
correct penile curvature is based on pre-operative assess-
ment of penile length, the degree of the curvature, and
erectile function status. The results of the different surgical
approaches are presented in Table 1. It must be emphasised
that there are no randomised controlled trials available
149 Penile Curvature
addressing surgery in Peyronies disease. The treatment algo-
rithm is presented in Figure 1.
Recommendations on surgical treatment for
penile curvature
LE GR
Surgery is indicated when Peyronies disease
is stable for at least 3 months (without pain or
deformity deterioration), which usually occurs
after 12 months from the onset of symptoms,
and intercourse is compromised by the
deformity.
3 C
Penile length, curvature severity, erectile func-
tion (including response to pharmacotherapy in
case of erectile dysfunction) and patient expec-
tations must be assessed prior to surgery.
3 C
Tunical shortening procedures, especially
plication techniques are the first treatment
options for congenital penile curvature and for
Peyronies disease with adequate penile length,
curvature < 60 and absence of special
deformities (hour-glass, hinge).
2b B
Grafting techniques are the preferred treatment
option for patients with Peyronies disease with
no adequate penile length, curvature > 60 and
presence of special deformities (hour-glass,
hinge).
2b B
Penile prosthesis implantation, with or without
any additional procedure (modelling, plication
or grafting), is recommended in Peyronies
disease patients with erectile dysfunction not
responding to pharmacotherapy.
2b B
150 Penile Curvature
Table 1: Results of surgical treatments for Peyronies dis-
ease (data from different, non-comparable studies)
Tunical shortening
procedures
Tunical
lengthening
procedures
Nesbit Plication Grafts
Penile shortening 4.7-30.8% 41-90% 0-40%
Penile straightening 79-100% 58-100% 74-100%
Persistent or
recurrent curvature
4-26.9% 7.7-10.6% 0-16.7%
Post-operative
erectile dysfunction
0-13% 0-22.9% 0-15%
Penile hypoesthesia 2-21% 0-21.4% 0-16.7%
Technical
modifications
1 At least 3 Many types
of grafts and
techniques
used
151 Penile Curvature
Treatment of Peyronies disease
Discuss natural history of the disease
Reassure patient that Peyronies is a benign disease
Discuss current treatment modalities
Shared decision-making
Conservative treatment Surgical treatment
No ED
Short penis
Curvature > 60
Presence of special
deformities (hour-glass,
hinge)
Adequate penis length
Curvature < 60
Absence of special
deformities (hour-glass,
hinge)
Tunica lengthening
procedures
Nesbit or plication
procedures
No
Penile
prosthesis
(remodelling,
plaque)
Active disease
(pain, deformity deterioration, no
calcication on US)
Stable disease
(no pain, no deformity deterioration,
calcication plaques on US)
Yes
ED
Response
to
treatment
This short booklet text is based on the more comprehensive EAU
guidelines (978-90-79754-83-0), available to all members of the
European Association of Urology at their website,
http://www.uroweb.org.
Figure 1: Treatment algorithm for Peyronies disease
152 Male Infertility
GUIDELINES FOR THE INVESTIGATION
AND TREATMENT OF MALE
INFERTILITY
(Text update March 2013)
A. Jungwirth, T. Diemer, G.R. Dohle, A. Giwercman, Z. Kopa,
H. Tournaye, C. Krausz
Eur Urol 2004 Nov;46(5):555-8
Eur Urol 2012 Jan;61(1):159-63
Definition
Infertility is the inability of a sexually active, non-contracept-
ing couple to achieve spontaneous pregnancy in one year.
(WHO, 1995).
About 15% of couples do not achieve pregnancy within 1 year
and seek medical treatment for infertility. Eventually, less
than 5% remain unwillingly childless.
Prognostic factors
The main factors influencing the prognosis in infertility are:
duration of infertility;
primary or secondary infertility;
results of semen analysis;
age and fertility status of the female partner.
As a urogenital expert, the urologist should examine any male
with fertility problems for urogenital abnormalities.
Diagnosis
The diagnosis of male fertility should focus on a number of
prevalent disorders (Table 1). Simultaneous assessment of the
female partner is preferable, even if abnormalities are found in
153 Male Infertility
the male, since data show that in 1 out of 4 couples both male
and female partners have pathological findings.
Table 1: Reasons for a reduction in male fertility
Congenital factors (cryptorchidism and testicular
dysgenesis, congenital absence of the vas deferens)
Acquired urogenital abnormalities (obstructions, testicular
torsion, testicular tumour, orchitis)
Urogenital tract infections
Increased scrotal temperature (e.g. due to varicocele)
Endocrine disturbances
Genetic abnormalities
Immunological factors (autoimmune diseases, antisperm
antibodies)
Systemic diseases (diabetes, renal and liver insufficiency,
cancer, hemochromatosis)
Exogenous factors (medications, toxins, irradiation)
Lifestyle factors (obesity, smoking, drugs, anabolic steroids)
Idiopathic (40-50% of cases)
Semen analysis
Semen analysis forms the basis of decisions concerning fur-
ther treatment. Analysis should be performed in a laboratory
adhering to national quality control standards (Table 2).
Table 2: Lower reference limits (5th centiles and 95%
confidence intervals) for semen characteristics*
Parameter Lower reference
limit (95% CI)
Semen volume (mL) 1.5 (1.4-1.7)
Total sperm number (10
6
per ejaculate) 39 (33-46)
Sperm concentration (10
6
per mL) 15 (12-16)
154 Male Infertility
Total motility (PR+NP, %) 40 (38-42)
Progressive motility (PR, %) 32 (31-34)
Vitality (live spermatozoa, %) 58 (55-63)
Sperm morphology (normal forms, %) 4 (3.0-4.0)
Other consensus threshold values
pH 7.2
Peroxidase-positive leukocytes
(10
6
per mL)
< 1.0
MAR test (motile spermatozoa with
bound particles, %)
< 50
Immunobead test (motile spermatozoa
with bound beads, %)
< 50
Seminal zinc (mol/ejaculate) 2.4
Seminal fructose (mol/ejaculate) 13
Seminal neutral glucosidase
(mU/ejaculate)
20
*WHO Manual for Semen Analysis, 5th edn, 2010.
Recommended number of semen analyses
If values are normal, one test should suffice. If the results are
abnormal, semen analysis should be repeated. It is impor-
tant to distinguish between oligozoospermia (< 15 million
spermatozoa/mL), asthenozoospermia (< 40% motile sper-
matozoa) and teratozoospermia (< 4% normal forms). Quite
often, all three pathologies occur at the same time, i.e. as
oligo-astheno-teratozoospermia (OAT) syndrome. In extreme
cases of OAT syndrome (< 1 million spermatozoa/mL), just as
with azoospermia, there is an increased incidence of genetic
abnormalities and/or obstruction of the male genital tract.
Hormonal investigation
Endocrine malfunctions are more prevalent in infertile men
than in the general population, but are still quite uncommon.
155 Male Infertility
Hormonal screening can be limited to determining the levels
of follicle stimulating hormone (FSH), luteinizing hormone
(LH), testosterone and sex hormone binding globulin (SHBG)
in cases of abnormal semen parameters. In men diagnosed
with azoospermia or extreme OAT, it is important to dis-
tinguish between obstructive and non-obstructive causes.
Criteria with a reasonable predictive value for obstruction
are a normal FSH with bilaterally normal testicular volume.
However, 29% of infertile men with a normal FSH appear to
have defective spermatogenesis.
Hypergonadotrophic hypogonadism (elevated FSH/LH)
Impaired spermatogenesis associated with elevated levels of
gonadotrophins is a common problem and is due to primary
testicular failure. Causes include:
Congenital - Klinefelters syndrome, anorchia,
cryptorchidism, testicular dysgenesis, Y chromosome
microdeletions;
Acquired - after orchitis, testicular torsion, testicular
tumour, systemic illness, cytotoxic therapy.
Hypogonadotrophic hypogonadism (low FSH/LH)
Low levels of gonadotrophins due to dysfunction of the pitui-
tary gland or hypothalamus are rare and may occur as a result
of:
Congenital anomalies - idiopathic Hypogonadotrophic
Hypogonadism (iHH), Kallmanns syndrome,
Prader-Willi syndrome;
Acquired anomalies - acquired hypothalamic/pituitary
gland diseases (malignant CNS tumours, pituitary
adenoma, hyperprolactinaemia, granulomatous illness,
hemochromatosis);
Exogenous factors - drugs (anabolic steroids, obesity,
irradiation).
156 Male Infertility
If unexplained hypogonadotrophic hypogonadism is present,
the medical examination should include magnetic resonance
imaging (MRI) of the pituitary gland.
Microbiological assessment
Indications for microbiological assessment include abnormal
urine samples, urinary tract infections, male accessory gland
infections (MAGI) and sexually transmitted diseases (STDs).
White blood cells detected in a semen sample, in combination
with a small ejaculate volume, may point to a (partial) obstruc-
tion of the ejaculatory ducts caused by a (chronic) infection of
the prostate or seminal vesicles. Genital infections may
instigate the production of spermatotoxic free oxygen
radicals. Neisseria gonorrhoea and Chlamydia trachomatis
infections can also cause obstruction of the genital tract.
Although antibiotic procedures for MAGI might provide
improvement in sperm quality, therapy does not necessarily
increase the probability of conception.
Genetic evaluation
A substantial number of andrological fertility disorders that
used to be described as idiopathic male infertility have a
genetic origin. An extensive family history and karyotype
and Y-chromosome deletion analysis will detect a number of
these disorders, not only providing a diagnosis, but also ena-
bling appropriate genetic counselling. The latter may be very
important with the advent of intracytoplasmic sperm injection
(ICSI), because genetic defects may be transferred and a bal-
anced translocation of the infertile father may become unbal-
anced in the offspring.
Chromosomal abnormalities are more common in men with
OAT and with azoospermia, and karyotyping is recommended
in these men both for diagnosis purposes and for genetic
counselling. The most common sex chromosome abnormality
157 Male Infertility
is Klinefelters syndrome (47, XXY), which affects around 14%
of men diagnosed with azoospermia. Klinefelters syndrome is
characterised by hypergonadotrophic hypogonadism which
may be associated with eunuchoid features and/or gynaeco-
mastia. Both testicles are very small due to extensive tubular
sclerosis. In 60% of all patients, testosterone levels decrease
with age requiring androgen replacement.
Furthermore, chromosome translocations and deletions can
be found, which may be hereditary and cause habitual abor-
tion and congenital malformations in the offspring. In cases
of azoospermia or severe OAT, there may be deletions in the
azoospermic factor (AZF) region of the Y-chromosome and
testing is advised. The prevalence of Y deletions is consider-
able (around 5%) in this group of patients. The presence of a
Y deletion means that the defect will be passed to sons, who
will then also be affected by spermatogenic disturbances or
failure.
When performing ICSI with surgically retrieved sperm or
ejaculated spermatozoa, based on a diagnosis of congenital
bilateral/unilateral absence of the vas deferens (CAVD), both
the male and the female partner should be tested for muta-
tions in the cystic fibrosis transmembrane regulator (CFTR)
gene. Apart from causing cystic fibrosis (CF), this gene is also
associated with CAVD; over 85% of all males diagnosed with
CAVD also test positive for two CFTR-gene mutations when
the entire gene is sequenced. In cases of a homozygous CFTR
mutation carrier with a mutation carrier partner, depending
on the mutations involved, there is a 50% chance of a child
with CF or CAVD. Genetic counselling is mandatory in these
cases.
Ultrasonography
Ultrasonography (US) is a useful tool for locating intrascrotal
158 Male Infertility
lesions. Colour Doppler US of the scrotum can detect a vari-
cocele in around 30% of subfertile males. Testicular tumours
can be found in 0.5%, and testicular microcalcifications (a
potentially premalignant condition) are detected in around
2-5% of subfertile males, especially patients diagnosed with a
history of cryptorchidism. Transrectal ultrasonography (TRUS)
is indicated in men with a low volume of ejaculate (< 1.5 mL)
to exclude obstruction of the ejaculatory ducts caused by a
midline prostatic cyst or stenosis of the ejaculatory ducts.
Testicular biopsy
Testicular biopsy is usually performed as part of a therapeutic
process in azoospermic patients (testicular sperm retrieval
- TESE) who decide to undergo ICSI. Indications for perform-
ing a diagnostic testicular biopsy could be azoospermia or
extreme OAT, in the presence of a normal testicular volume
and normal FSH levels. The biopsy is aimed at differentiating
between testicular insufficiency and obstruction of the male
genital tract. It is advised that, during the procedure, tissue
that contains spermatozoa is cryopreserved for future ICSI
attempts.
In addition, testicular biopsies are performed to detect car-
cinoma in situ of the testis in infertile men with testicular
microcalcifications and risk factors for testicular cancer (i.e.
male infertility, cryptorchidism, history of a testicular tumour,
testicular atrophy).
Pathological classifications are:
Absence of seminiferous tubules (tubular sclerosis);
Absence of germ cells (Sertoli cell only syndrome);
Maturation arrest - spermatogenesis arrested at different
stages (spermatogonia, spermatocytes or spermatides);
159 Male Infertility
Hypospermatogenesis - all cell types up to spermatozoa
are present, but there is a distinct decline in the number of
reproducing spermatogonia.
Treatment
Counselling
Lifestyle factors can impair semen quality, e.g. heavy smoking,
alcohol abuse, use of anabolic steroids, extreme sports (mara-
thon training, excessive strength sports), and an increase in
scrotal temperature through thermal underwear, sauna or hot
tub use, or occupational exposure to heat sources. A consid-
erable number of drugs can affect spermatogenesis.
Medical (hormonal) treatment
Antioxidant treatment (folic acid, vitamin E, zinc, selenium)
may have a positive influence on semen quality but infertile
couples should be advised that current evidence on their
benefit to promote pregnancy is inconclusive. No studies
have confirmed that hormonal therapies, such as human
menopausal gonadotrophin (HMG)/human chorionic gona-
dotrophin (HCG), androgen, anti-oestrogens (clomiphene and
tamoxifen), prolactin inhibitors (bromocriptine) and steroids,
have improved pregnancy rates in men with idiopathic OAT.
However, some primarily endocrinological pathologies can be
treated medically, including:
Low testosterone: clomiphene citrate 50 mg/day or
tamoxifen 20 mg/day;
Hypogonadotrophic hypogonadism: start HCG 1500 IU 3
times per week, and add HMG or FSH 75-150 IU 3 times per
week, until spermatogenesis occurs;
Hyperprolactinaemia: dopamine agonists.
In patients with anti-sperm antibodies, high-dose steroids are
not recommended because of serious side-effects and ques-
tionable benefit.
160 Male Infertility
Surgical treatment
Varicocele
The treatment of varicocele is a controversial subject, mainly
based on whether there is an actual need to treat varicocele
in infertile men. There is evidence of improved semen param-
eters after successful varicocele treatment. Current informa-
tion supports the hypothesis that in some men, the presence
of varicocele is associated with progressive testicular damage
from adolescence onwards and consequent reduction in
fertility. Although treatment of varicocele in adolescents may
be effective, there is a significant risk of over-treatment. In
cases of normal semen analysis and in men with a subclini-
cal varicocele, there appears to be no benefit from treatment
compared with observation. Varicocele repair, however,
seems effective in couples in whom the men has a oligo- or
asthenozoospermia, a clinical varicocele, and otherwise unex-
plained infertility.
Microsurgery/vasovasostomy and epididymovasostomy
Only urologists with experience in microsurgery should under-
take these procedures using an operating microscope. The
likelihood of initiating pregnancy is inversely proportional to
the obstruction interval and becomes less than 50% after
8 years. Other important prognostic factors are the qual-
ity of the semen after the procedure and the partners age.
In approximately 15% of men who have undergone a suc-
cessful vasovasostomy, sperm quality deteriorates to the
level of azoospermia or extreme oligospermia within 1 year.
Sometimes an epididymal obstruction coexists, especially
in men with a long interval between vasectomy and vasova-
sostomy. In these men a vaso-epididymostomy is indicated.
Considering that a vaso-epididymostomy has a limited effect
on pregnancy rates (20-30%), it is advisable to combine this
procedure with microsurgical epididymal sperm aspira-
tion (MESA), and cryopreserve the harvested spermatozoa
161 Male Infertility
for ICSI. The indications for vaso-epididymostomy include
obstructions at the level of the epididymis in the presence
of a normal spermatogenesis (testicular biopsy). Poor sperm
quality and sometimes sperm antibodies after successful
vasectomy repair may prevent spontaneous pregnancy and
assisted reproduction is indicated.
MESA/TESE
MESA/testicular sperm extraction (TESE) in combination with
ICSI is indicated in men with obstructive azoospermia when
reconstruction (vasovasostomy, vaso-epididymostomy) can-
not be performed or is unsuccessful. An alternative would
be percutaneous aspiration of spermatozoa from the caput
epididymis (PESA). In 50-60% of men with non-obstructive
azoospermia (NOA), spermatozoa can be found in the testis.
Some authors recommend taking several testicular samples,
while others advocate microsurgical harvesting of sperma-
tozoa. So far, no clinical or laboratory parameter has been
shown to be useful in predicting sperm harvesting in men with
NOA. In case of AZFa and AZFb microdeletions, no spermato-
zoa can be retrieved.
Transurethral incision of ejaculatory ducts or midline
prostatic cyst
Distal obstructions of the genital tract are commonly caused
by infections of the prostatic urethra and the accessory
glands or by a cyst in the midline of the prostate. Treatment
of the obstruction by transurethral incision of the cyst or the
ejaculatory ducts (TURED) may lead to an increase in semen
quality and, occasionally, spontaneous pregnancy. Long-term
results, however, are disappointing.
Disorders of ejaculation
Retrograde ejaculation and anejaculation can occur:
In neurological diseases, e.g. multiple sclerosis, diabetes
162 Male Infertility
mellitus (neuropathy) and spinal cord injuries;
Following prostate surgery, bladder neck surgery, sym-
pathectomy and retroperitoneal surgery, e.g. lymph node
dissections for testicular tumours;
During antidepressant therapy.
Diagnosis is based on the medical history of post-ejaculate
urine. Retrograde ejaculation should also be suspected if the
ejaculate volume is very low (partial retrograde ejaculation).
Treatment of retrograde ejaculation aimes at removing the
cause of the disorder or harvesting spermatozoa from the
urine after orgasm. Anejaculation can be treated by vibros-
timulation or electro-ejaculation techniques. It is possible to
induce ejaculation in around 90% of patients with spinal cord
injuries. However, the semen quality is often poor with a low
number of motile spermatozoa and increased rates of DNA
fragmentation. This accounts for the disappointing results of
assisted reproduction techniques in these men. TESE, in-vitro
fertilisation, and ICSI are often required.
Recommendations GR
Testicular biopsy is the best procedure to define the
histological diagnosis and possibility of finding sperm.
Spermatozoa should be cryopreserved for use in ICSI.
A
Men with NOA can be offered TESE with cryopreser-
vation of the spermatozoa to be used for ICSI.
A
Testing for microdeletions is not necessary in men
with OA (with normal FSH) when ICSI is used because
spermatogenesis should be normal.
A
Men with severely damaged spermatogenesis (sper-
matozoa < 5 million/mL) should be advised to undergo
Yq microdeletion testing for both diagnostic and prog-
nostic purposes. Yq microdeletion also has important
implications for genetic counselling (see below).
A
163 Male Infertility
If complete AZFa or AZFb microdeletions are detect-
ed, micro-TESE is not necessary because it is extreme-
ly unlikely that any sperm will be found.
A
If a man with Yq microdeletion and his partner wish to
proceed with ICSI, they should be advised that micro-
deletions will be passed to sons, but not to daughters.
A
Standard karyotype analysis should be offered to all
men with damaged spermatogenesis
(spermatozoa <10 million/mL) who are seeking fertility
treatment by IVF.
B
Genetic counselling is mandatory in couples with a
genetic abnormality found in clinical or genetic inves-
tigation and in patients who carry a (potential) inherit-
able disease.
A
When a man has structural abnormalities of the vas
deferens (unilateral or bilateral absence), he and his
partner should be tested for CF gene mutations.
A
Aetiological treatments for ejaculatory disorders
should be offered before sperm collection and ART is
performed.
B
This short booklet text is based on the more comprehensive EAU
guidelines (978-90-79754-71-7), available to all members of the
European Association of Urology at their website,
http://www.uroweb.org.
164 Male Hypogonadism
GUIDELINES ON
MALE HYPOGONADISM
G.R. Dohle (chair), S. Arver, C. Bettocchi, S. Kliesch, M. Punab,
W. de Ronde
Introduction
Male hypogonadism is a clinical syndrome caused by andro-
gen deficiency. It may adversely affect multiple organ func-
tions and quality of life. Androgens play a crucial role in the
development and maintenance of male reproductive and
sexual functions. Low levels of circulating androgens can
cause disturbances in male sexual development, resulting
in congenital abnormalities of the male reproductive tract.
Later in life, this may cause reduced fertility, sexual dysfunc-
tion, decreased muscle formation and bone mineralisation,
disturbances of fat metabolism, and cognitive dysfunction.
Testosterone levels decrease as a process of ageing: signs
and symptoms caused by this decline can be considered a
normal part of ageing. However, low testosterone levels are
also associated with several chronic diseases, and sympto-
matic patients may benefit from testosterone treatment.
Androgen deficiency increases with age; an annual decline
in circulating testosterone of 0.4-2.0% has been reported.
In middle-aged men, the incidence was found to be 6%. It is
more prevalent in older men, in men with obesity, those with
co-morbidities, and in men with a poor health status.
Aetiology and forms
Male hypogonadism can be classified in 4 forms:
1. Primary forms caused by testicular insufficiency.
2. Secondary forms caused by hypothalamic-pituitary
dysfunction.
165 Male Hypogonadism
3. Late onset hypogonadism.
4. Male hypogonadism due to androgen receptor
insensitivity.
The main causes of these different forms of hypogonadism
are highlighted in Table 1.
The type of hypogonadism has to be differentiated, as this has
implications for patient evaluation and treatment and enables
identification of patients with associated health
problems.
Table 1: Different forms of male hypogonadism and main
causes
Primary forms
(testicular insufficiency)
Main causes
Congenital forms Klinefelter syndrome
Testicular dysgenesis
(cryptorchidism)
Congenital anorchia
Acquired forms Testicular malignancy
Orchitis
Medications (chemotherapy)
Systemic diseases
Acquired anorchia
Secondary forms
(hypothalamic-pituitary
dysfunctions)
Main causes
Congenital forms Kallmann syndrome
Idiopathic
hypogonadotrophic
hypogonadism (IHH)
166 Male Hypogonadism
Acquired forms Pituitary tumour
(prolactinoma)
Drugs
Systemic disease (renal
failure, haemochromatosis,
hypothyroidism, trauma,
infections)
Abuse of anabolic steroids
Morbid obesity
Radiotherapy
Late onset hypogonadism Ageing
(Combined testicular and
hypothalamic pituitary
insufficiency)
Obesity
Chronic diseases
Poor health status
Androgen receptor
insensitivity
Partial androgen insensitivity
syndrome (PAIS)
Diagnosis
The diagnosis of male hypogonadism is based on clinical
symptoms and signs of androgen deficiency (Tables 2 and 3),
together with consistently low serum testosterone levels.
167 Male Hypogonadism
Table 2: Signs and symptoms suggesting prepubertal-onset
hypogonadism
Small testes
Cryptorchidism
Gynaecomastia
High voice
Unclosed epiphyses
Linear growth into adulthood
Eunuchoid habitus
Sparse body/facial hair
Infertility
Low bone mass
Sarcopenia
Reduced sexual desire/activity
Table 3: Signs and symptoms associated with late-onset
hypogonadism
Loss of libido
Erectile dysfunction
Sarcopenia
Low bone mass
Depressive thoughts
Changes in mood, fatigue and anger
Sleep disturbances
Loss of body hair
Hot flushes
Loss of vigour
Insulin resistance
Metabolic syndrome
Visceral obesity
Gynaecomastia
168 Male Hypogonadism
Diminished cognitive functions
Routine screening for testosterone deficiency is not indi-
cated. However, testosterone assessment should be done in
men with:
Pituitary mass, following radiation involving the sellar
region and other diseases in the hypothalamic and sellar
region.
End-stage renal disease receiving haemodialysis.
Treatment with medications that cause suppression of
testosterone levels e.g. corticosteroids and opiates;
Moderate to severe chronic obstructive lung disease;
Infertility.
Osteoporosis or low-trauma fractures.
Human immunodeficiency virus (HIV) infection with sarco-
penia.
Type 2 diabetes.
Acquired hypogonadotropic hypogonadism (secondary forms)
can be caused by some drugs, hormones, anabolic steroids
and by tumours of the pituitary gland. Imaging (CT or MRI)
of the sellar region and complete endocrine work-up is
requested when a pituitary tumour is suspected.
Recommendations for screening GR
Screening for testosterone deficiency is only recom-
mended in adult men with consistent and preferably
multiple signs and symptoms, listed in Tables 2 and 3.
C
Adult men with established severe hypogonadism
should be screened for concomitant osteoporosis.
B
Total testosterone assessment should be repeated at
least on two occasions with a reliable method.
A
169 Male Hypogonadism
- In men with total testosterone levels close to the
lower normal range (8-12 nmol/l), the free testoste-
rone level should be measured to strengthen the
laboratory assessment.
- In men with suspected or known abnormal sex
hormone-binding globulin (SHBG) levels, free
testosterone should also be included.
Treatment
The aim of treatment is to restore testosterone levels to the
physiological range and thereby improve the patients quality
of life. Indications and contraindications are listed in Tables 4
and 5.
Table 4: Indications for testosterone treatment
Adult men with consistent and preferably multiple signs and
symptoms of hypogonadism (listed in Tables 2 and 3) and
low testosterone
Delayed puberty (idiopathic, Kallmann syndrome)
Klinefelter syndrome with hypogonadism
Sexual dysfunction and low testosterone
Low muscle strength and bone mass in hypogonadism
Hypopituitarism
Testicular insufficiency and symptomatic hypogonadism
170 Male Hypogonadism
Table 5: Contraindications against testosterone treatment
Prostate cancer
Prostate-specific antigen (PSA) > 4 ng/mL
Male breast cancer
Severe sleep apnoea
Male infertility
Haematocrit > 50%
Severe lower urinary tract symptoms due to benign
prostatic enlargement
Choice of treatment
Testosterone replacement therapy (TRT) is safe and effective
and the agents are available as oral preparations, intramuscu-
lar injections, and transdermal gel or patches (Table 6).
Table 6: Testosterone preparations for replacement
therapy
Formulation Administration Advantages Dis-
advantages
Testosterone
undecanoate
Oral; 2-6 cps
every 6 h
Absorbed
through the
lymphatic
system, with
consequent
reduction of
liver involve-
ment
Variable
levels of
testosterone
above and
below the
mid-range.
Need for
several doses
per day with
intake of
fatty food
171 Male Hypogonadism
Testosterone
cypionate
Intramuscular;
one injection
every 2-3 weeks
Short-acting
preparation
that allows
drug with-
drawal in
case of onset
of side effects
Possible
fluctuation of
testosterone
levels
Testosterone
enanthate
Intramuscular;
one injection
every 2-3 weeks
Short-acting
preparation
that allows
drug with-
drawal in
case of onset
of side effects
Possible
fluctuation of
testosterone
levels
Testosterone
undecanoate
Intramuscular;
one injection
every 10-14
weeks
Steady-state
testosterone
levels without
fluctuation
Long-acting
preparation
that cannot
allow drug
withdrawal
in case of
onset of side
effects
Transdermal
testosterone
Gel or skin
patches; daily
application
Steady-state
testosterone
level without
fluctuation
Skin irritation
at the site of
application
and risk of
interpersonal
transfer
172 Male Hypogonadism
Sublingual
testosterone
Sublingual; daily
doses
Rapid absorp-
tion and
achievement
of physiologi-
cal serum
level of testo-
sterone
Local irrita-
tion
Buccal
testosterone
Buccal tablet;
two doses per
day
Rapid absorp-
tion and
achievement
of physiologi-
cal serum
level of testo-
sterone
Irritation and
pain at the
site of appli-
cation
Subdermal
depots
Subdermal
implant every 5-7
months
Long duration
and constant
serum testo-
sterone level
Risk of infec-
tion and
extrusion of
the implants
In patients with secondary hypogonadism, anti-oestrogens
or hormonal stimulation with hCG and FSH or alternatively
GnRH can restore testosterone production.
Recommendations GR
The patient should be fully informed about expected
benefits and side effects of each treatment option. The
selection of the preparation should be a joint decision
by an informed patient and the physician.
A
Short-acting preparations may initially be preferred to
long-acting depot administration when starting treat-
ment. Patients can switch to a long-acting depot if
preferred and side effects are absent or minimal.
B
173 Male Hypogonadism
Human chorionic gonadotrophin (hCG) treatment can
only be recommended for hypogonadal patients who
are receiving simultaneous fertility treatment.
B
Risk factors in testosterone treatment
Case reports and small cohort studies point to a possible
correlation between TRT and the onset of breast cancer,
but there is as yet a lack of strong evidence for this rela-
tionship.
Randomised controlled trials support the hypothesis that
TRT does not result in changes in prostatic histology.
However, there are not yet data available that show long-
term prostatic safety of TRT.
Testosterone therapy is not related to the development
of de novo cardiovascular events. However, patients with
severe cardiovascular diseases should be screened first by
a cardiologist before TRT is initiated.
Recommendations for initiation of treatment GR
Haematological, cardiovascular, breast and prostatic
assessment should be performed before the start of
treatment.
A
Men with severe cardiovascular co-morbidity should
be assessed by a cardiologist before TRT is initiated
and there should be close cardiovascular monitoring
during TRT.
C
Prostate health should be assessed by digital rectal
examination (DRE) and PSA before the start of TRT.
A
In patients treated for localised prostate cancer
and without signs of prostate cancer recurrence,
testosterone therapy should not start before at least 1
year of follow-up.
C
174 Male Hypogonadism
Recommendations for monitoring GR
The response to treatment (symptoms and
testosterone serum levels) should be assessed 3, 6 and
12 months after the onset of treatment, and thereafter
annually.
C
In men with an abnormal bone mineral density (BMD),
BMD measurements should be repeated 6 and 12
months after the start of TRT and thereafter annually.
C
Haematocrit should be monitored at 3, 6 and 12
months and thereafter annually. The testosterone
dosage should be decreased, or therapy discontinued
if the haematocrit increases above normal levels.
C
Prostate health should be monitored by PSA testing at
3, 6 and 12 months and thereafter annually.
C
Routine screening of potential cardiovascular side
effects is not indicated in men receiving TRT.
A
This short booklet text is based on the more comprehensive EAU
guidelines (978-90-79754-83-0), available to all members of the
European Association of Urology at their website,
http://www.uroweb.org.
175 Urinary Incontinence
GUIDELINES ON URINARY
INCONTINENCE
(Text update March 2013)
M.G. Lucas (chair), D. Bedretdinova, J.L.H.R. Bosch,
F. Burkhard, F. Cruz, D.J.M.K. de Ridder, A. Nambiar, A. Tubaro,
R.S. Pickard
This pocket version aims to synthesise the important clini-
cal messages described in the full text and is presented as
a series of evidence summaries and graded action based
recommendations, which follow the standard for levels of evi-
dence used by the EAU (see Introduction chapter).
ASSESSMENT AND DIAGNOSIS
History and Physical Examination
Although there is no evidence to support this, there is abso-
lute consensus of expert opinion that this is an essential step.
Recommendations 1 GR
Take a history to include the following;
Type of incontinence (stress, urge or mixed)
Timing and severity
Any associated urinary symptoms
Obstetric and gynaecological history
Any comorbidities
Medication review
A*
176 Urinary Incontinence
Do a physical examination to include:
Abdominal exam to detect bladder enlargement or
abdominal/pelvic mass
Perineal examination
Digital vaginal or rectal examination
Assess oestrogen status of woman
Assess voluntary pelvic floor contraction
A*
Consider early referral to specialist if:
Urinary incontinence associated with pain
Haematuria
History of recurrent urinary tract infection
Previous pelvic surgery or radiotherapy
Constant leak suspicious of fistula
Any voiding difficulty
Suspicion of neurological disease
A*
* Given Grade A because, despite an absence of evidence,
expert opinion assigns absolute importance to these steps
Questionnaires
Recommendations 2 GR
Use a validated questionnaire when standardised
assessment of severity and monitoring of effects of
treatment is required, e.g. in trials or registries or for
audit purposes.
C
Voiding diaries
Recommendations 3 GR
Use a frequency volume chart to evaluate co-existing
storage and voiding dysfunction in patients with
urinary incontinence.
A
Use a diary duration of between 3 and 7 days. B
177 Urinary Incontinence
Urinalysis and UTI
Recommendations 4 GR
Do urinalysis as part of the initial assessment of a
patient with urinary incontinence.
A
In a patient with urinary incontinence, treat a
symptomatic urinary tract infection appropriately (see
EAU Guidelines on Urological Infections).
A
Do not treat asymptomatic bacteriuria in elderly
patients to improve urinary incontinence.
B
Post-voiding residual volume
Recommendations 5 GR
Use US to measure post-voiding residual. A
Measure post-voiding residual in patients with urinary
incontinence who have voiding dysfunction.
B
Measure post-voiding residual when assessing
patients with complicated urinary incontinence.
C
Post-voiding residual should be monitored in patients
receiving treatments that may cause or worsen
voiding dysfunction.
B
Urodynamics
Recommendations 6
(NB: These refer only to neurologically intact adults
with urinary incontinence)
GR
Clinicians carrying out urodynamics in patients with
urinary incontinence should:
Ensure that the test replicates the patients
symptoms
Interpret results in context of the clinical problem
Check recordings for quality control
Remember there may be physiological variability
within the same individual.
C
178 Urinary Incontinence
Advise patients that the results of urodynamics may
be useful in discussing treatment options, although
there is limited evidence that performing urodynamics
will alter the outcome of treatment for urinary
incontinence.
C
Do not routinely carry out urodynamics when offering
conservative treatment for urinary incontinence.
B
Perform urodynamics if the findings may change the
choice of invasive treatment.
B
Do not routinely carry out urethral pressure
profilometry.
C
Pad testing
A well-designed continence pad will contain any urine leaked
within a period of time and this has therefore been used as
a way of quantifying leakage. Although the International
Continence Society has attempted to standardise pad testing,
there remain differences in the way patients are instructed to
undertake activity during the test.
Recommendations 7 GR
Use a pad test when quantification of urinary inconti-
nence is required.
C
Use repeat pad test after treatment if an objective
outcome measure is required.
C
Imaging
Recommendation 8 GR
Do not routinely carry out imaging of the upper or
lower urinary tract as part of the assessment of
uncomplicated stress urinary incontinence in women.
A
CONSERVATIVE TREATMENT
Conventional medical practice encourages the use of simple,
179 Urinary Incontinence
relatively harmless, interventions before resort to those asso-
ciated with higher risks.
Simple Medical interventions
Correction of Underlying disease/cognitive impairment
Numerous conditions exacerbate UI or make it more likely to
occur, whether or not they play any part in the patho-
physiology of leakage. These conditions include:
cardiac failure
chronic renal failure
diabetes
chronic obstructive pulmonary disease
neurological disorders
stroke
dementia
multiple sclerosis
general cognitive impairment
sleep disturbances e.g. sleep apnoea.
Adjustment of medication
There is very little evidence of benefit from the adjustment of
medication. There is also a theoretical risk, at least, that stop-
ping or altering medication may bring with it more harm than
good.
Recommendations 9 GR
Take a drug history from all patients with urinary
incontinence.
A
Inform women with urinary incontinence that begins
or worsens after starting systemic oestrogen replace-
ment therapy that it may cause urinary incontinence.
A
Review any new medication associated with the
development or worsening of urinary incontinence.
C
180 Urinary Incontinence
Constipation
Several studies have shown strong associations between
constipation, urinary incontinence and overactive bladder.
Constipation can be improved by behavioural and medical
treatments.
Recommendations 10 GR
For adults with urinary incontinence, treat co-existing
constipation.
C
Containment (pads etc)
Recommendations 11 GR
Offer pads when containment of urinary incontinence
is needed.
B
Adapt the choice of pad to the type and severity of
urinary incontinence and the patients needs.
A
Offer catheterisation to manage urinary incontinence
when no other treatments can be considered.
B
Offer condom catheters to men with urinary
incontinence without significant residual urine.
A
Offer to teach intermittent catheterisation to manage
urinary incontinence associated with retention of
urine.
A
Do not routinely offer intravaginal devices as
treatment for incontinence.
B
Do not use penile clamps for control of urinary
incontinence in men.
A
Lifestyle Changes
Examples of lifestyle factors that may be associated with
incontinence include obesity, smoking, level of physical activ-
ity and diet. It may therefore be possible to improve urinary
181 Urinary Incontinence
incontinence by beginning lifestyle interventions, such as
weight loss, fluid restriction, reduction of caffeine or alcohol
intake, limiting heavy activity and stopping smoking.

Recommendations 12 GR
Encourage obese women suffering from any urinary
incontinence to lose weight (> 5%).
A
Advise adults with urinary incontinence that reducing
caffeine intake may improve symptoms of urgency
and frequency but not incontinence.
B
Patients with abnormally high or abnormally low fluid
intake should be advised to modify their fluid intake
appropriately.
C
Counsel female athletes experiencing urinary
incontinence with intense physical activity that it will
not predispose to urinary incontinence in later life.
C
Patients with urinary incontinence who smoke should
be given smoking cessation advice in line with good
medical practice although there is no definite effect
on urinary incontinence.
A
Behavioural and physical therapies
Recommendations 13 GR
Offer supervised pelvic floor muscle training, lasting
at least 3 months, as a first-line therapy to women
with stress or mixed urinary incontinence.
A
Pelvic floor muscle training programmes should be as
intensive as possible.
A
Offer pelvic floor muscle training to elderly women
with urinary incontinence.
B
Consider using biofeedback as an adjunct in women
with stress urinary incontinence.
A
182 Urinary Incontinence
Offer supervised pelvic floor muscle training to
continent women in their first pregnancy to help
prevent incontinence in the postnatal period.
A
Offer instruction on pelvic floor exercises to men
undergoing radical prostatectomy to speed recovery
of urinary incontinence.
B
Offer bladder training as a first-line therapy to adults
with urge urinary incontinence or mixed urinary
incontinence.
A
Offer timed voiding to adults with urinary
incontinence, who are cognitively impaired.
A
Do not offer electrical stimulation with surface
electrodes (skin, vaginal, anal) alone for the treatment
of urinary incontinence.
A
Do not offer magnetic stimulation for the treatment
of urinary incontinence or overactive bladder in adult
women.
B
Do not offer posterior tibial nerve stimulation to
women or men who are seeking a cure for urge
urinary incontinence.
A
Offer, if available, posterior tibial nerve stimulation
as an option for improvement of urge urinary
incontinence in women, but not men, who have not
benefited from antimuscarinic medication.
B
Support other healthcare professionals in use of
rehabilitation programmes including prompted
voiding for care of elderly care-dependent people
with urinary incontinence.
A
183 Urinary Incontinence
DRUG TREATMENT OF URINARY INCONTINENCE
Antimuscarinics
Recommendations 14 GR
Offer immediate release or extended release formula-
tions of antimuscarinic drugs as initial drug therapy
for adults with urge urinary incontinence.
A
If immediate release formulations of antimuscarinic
drugs are unsuccessful for adults with urge urinary
incontinence, offer extended release formulations or
longer-acting antimuscarinic agents.
A
Consider using transdermal oxybutynin if oral
antimuscarinic agents cannot be tolerated due to dry
mouth.
B
Offer and encourage early review (of efficacy and side
effects) of patients on antimuscarinic medication for
urge urinary incontinence (< 30 days).
A
When prescribing antimuscarinic drugs to elderly
patients, be aware of the risk of cognitive side effects,
especially in those receiving cholinesterase inhibitors.
C
Avoid using oxybutynin immediate release in patients
who are at risk of cognitive dysfunction.
A
Consider use of trospium chloride in patients known
to have cognitive dysfunction.
B
Use antimuscarinic drugs with caution in patients
with cognitive dysfunction.
B
Do an objective assessment of mental function before
treating patients whose cognitive function may be at
risk.
C
Check mental function in patients on antimuscarinic
medication if they are at risk of cognitive dysfunction.
C
184 Urinary Incontinence
Adrenergic drugs
Recommendations 15 GR
Offer mirabegron extended release to people with
urge urinary incontinence depending on local licens-
ing arrangements.
B
Duloxetine
Recommendations 16 GR
Duloxetine should not be offered to women or men
who are seeking a cure for their urinary incontinence.
A
Duloxetine can be offered to women or men who are
seeking temporary improvement in incontinence
symptoms.
A
Duloxetine should be initiated using dose titration
because of high adverse effect rates.
A
Intravaginal Oestrogen
Recommendations 17 GR
Offer post-menopausal women with urinary inconti-
nence local oestrogen therapy, although the ideal
duration of therapy and best delivery method are
unknown.
A
Desmopressin
Recommendations 18 GR
Offer desmopressin to patients requiring occasional
short-term relief from urinary incontinence and inform
them that this drug is not licensed for this indication.
B
Do not use desmopressin for long-term control of uri-
nary incontinence.
A
185 Urinary Incontinence
SURGICAL TREATMENT
Generic principles of surgery:
Always discuss the purpose of surgery and the likely
benefits and risks, with the patient and/or carers
Explain alternative approaches even if they are not
available locally
Surgeons should be properly trained to do these
procedures and perform adequate numbers to maintain
expertise
Surgeons should be able to report their own outcomes for
any operation they offer and share this information with
their patient
Recommendations 19
(Surgery for women with uncomplicated stress
urinary incontinence)
GR
Offer the mid-urethral sling to women with uncom-
plicated stress urinary incontinence as the preferred
surgical intervention whenever available.
A
Offer colposuspension (open or laparoscopic) or
autologous fascial sling to women with stress urinary
incontinence if mid-urethral sling cannot be consid-
ered.
A
Inform older women with stress urinary incontinence
about the increased risks associated with surgery,
including the lower probability of success.
B
Inform women that any vaginal surgery may have an
impact on sexual function.
C
Warn women who are being offered a retropubic
insertion synthetic sling about the relatively higher
risk of peri-operative complications compared to
transobturator insertion.
A
Warn women who are being offered transobturator
insertion of mid-urethral sling about the higher risk
of pain and dyspareunia in the longer term.
A
186 Urinary Incontinence
Warn women undergoing autologous facial sling that
there is a high risk of voiding difficulty and the need
to perform clean intermittent self-catheterisation;
ensure they are willing and able to do so.
A
Do a cystoscopy as part of retropubic insertion of a
mid-urethral sling, or if difficulty is encountered during
transobturator sling insertion, or if there is a signifi-
cant cystocoele.
C
Women being offered a single-incision sling device
should be warned that long-term efficacy remains
uncertain.
C
Only offer new devices, for which there is no level 1
evidence base, as part of a structured research pro-
gramme.
A
Only offer adjustable mid-urethral sling as a primary
surgical treatment for stress urinary incontinence as
part of a structured research programme.
C
Do not offer bulking agents to women who are
seeking a permanent cure for stress urinary inconti-
nence.
A
Complicated Stress Urinary Incontinence in women
Recommendations 20
(Surgery for complicated stress urinary incontinence
in women)
GR
The choice of surgery for recurrent stress urinary
incontinence should be based on careful evaluation of
the individual patient including video-urodynamics.
C
Warn women with recurrent stress urinary
incontinence, that the outcome of a surgical
procedure, when used as a second-line treatment, is
generally inferior to its use as a first-line treatment,
both in terms of reduced efficacy and increased risk of
complications.
C
187 Urinary Incontinence
Consider secondary synthetic sling, colposuspension
or autologous sling as first options for women with
complicated stress urinary incontinence.
C
Do not undertake open colposuspension in women
who have had more than two previous operations for
urinary incontinence.
C
Implantation of AUS or ACT for women with com-
plicated stress urinary incontinence should only be
offered in high-volume centres.
C
Warn women receiving AUS or ACT that, even in high-
volume centres, there is a high risk of complications,
mechanical failure or a need for explantation.
C
AUS = artificial urinary sphincter; ACT = adjustable compres-
sion therapy.
Women with both Stress Urinary Incontinence and
Pelvic Organ Prolapse
Recommendations 21
(Women requiring surgery for bothersome POP who
have symptomatic or unmasked SUI)
GR
Offer simultaneous surgery for pelvic organ prolapse
and stress urinary incontinence.
A
Warn women of the increased risk of adverse events
with combined surgery compared to prolapse surgery
alone.
A
POP = pelvic organ prolapse; SUI = stress urinary inconti-
nence.
Recommendations 22
(Women requiring surgery for bothersome POP
without symptomatic or unmasked SUI)
GR
Warn women that there is a risk of developing de novo
stress urinary incontinence after prolapse surgery.
A
188 Urinary Incontinence
Inform women that the benefit of prophylactic stress
urinary incontinence surgery is uncertain.
C
Warn women that the benefit of surgery for stress
may be outweighed by the increased risk of adverse
events with combined surgery compared to prolapse
surgery alone.
A
POP = pelvic organ prolapse; SUI = stress urinary inconti-
nence.
Men with Stress Urinary Incontinence
Recommendations 23
(Surgical treatment of men with stress urinary
incontinence)
GR
Only offer bulking agents to men with mild post-pros-
tatectomy incontinence who desire temporary relief
of urinary incontinence symptoms.
C
Do not offer bulking agents to men with severe post-
prostatectomy incontinence.
C
Offer fixed slings to men with mild-to-moderate post-
prostatectomy incontinence.
B
Warn men that severe incontinence, prior pelvic radio-
therapy or urethral stricture surgery, may worsen the
outcome of fixed male sling surgery.
C
Offer AUS to men with moderate-to-severe post-
prostatectomy incontinence.
B
Implantation of AUS or ACT for men should only be
offered in high volume centres.
C
Warn men receiving AUS or ACT that, even in high
volume centres, there is a high risk of complications,
mechanical failure or a need for explantation.
C
Do not offer non-circumferential compression device
(ProACT) to men who have had pelvic radiotherapy.
C
AUS = artificial urinary sphincter; ACT = artificial compression
device.
189 Urinary Incontinence
Surgical interventions for Refractory Detrusor
Overactivity
Intravesical Botulinum Toxin injection
Recommendations 24 GR
Offer botulinum toxin A intravesical injections to
patients with urge urinary incontinence refractory to
antimuscarinic therapy.
A
Always check the botulinum toxin brand before
injection, as units among the available brands are not
interchangeable.
A
Offer onabotulinum toxin A 100 U as initial dose to
minimise the risk of urinary retention and urinary tract
infection.
A
Warn patients of the limited duration of response, the
possible prolonged need to self-catheterise (ensure
that they are willing and able to do so) and the
associated risk of urinary tract infection.
A
Patients should also be informed of the licensing
status of botulinum toxin A, and that long-term
adverse effects, although improbable, remain
uncertain.
A
Sacral Nerve Stimulation (neuromodulation)
Recommendation 25 GR
If available, offer to patients, who have urge urinary
incontinence refractory to conservative therapy, the
opportunity to be treated with sacral nerve neuro-
modulation before bladder augmentation or urinary
diversion is considered.
A
190 Urinary Incontinence
Augmentation Cystoplasty / Urinary Diversion
Recommendations 26 GR
Only offer augmentation cystoplasty to patients with
detrusor overactivity incontinence who have failed
conservative therapy, in whom the possibility of botu-
linum toxin and sacral nerve stimulation has been
discussed.
C
Warn patients undergoing augmentation cystoplasty
of the high risk of having to perform clean
intermittent self-catheterisation; ensure they are will-
ing and able to do so.
C
Do not offer detrusor myectomy as a treatment for
urinary incontinence.
C
Only offer urinary diversion to patients who have
failed less invasive therapies for the treatment of uri-
nary incontinence and who will accept a stoma.
C
Warn patients undergoing augmentation cystoplasty
or urinary diversion of the high risk of short-term and
long-term complications, and the possible small risk
of malignancy.
C
Life-long follow-up is recommended for patients who
have undergone augmentation cystoplasty or urinary
diversion.
C
Treatment of Mixed Urinary Incontinence
Recommendations 27 GR
Treat the most bothersome symptom first in patients
with mixed urinary incontinence.
C
Warn patients with mixed urinary incontinence that
the chance of success of pelvic floor muscle training
is less satisfactory than for stress urinary inconti-
nence alone.
B
191 Urinary Incontinence
Offer antimuscarinic drugs to patients with urgency-
predominant mixed urinary incontinence.
A
Warn patients with mixed urinary incontinence that
surgery is less likely to be successful than surgery in
patients with stress urinary incontinence alone.
A
Older People with Urinary Incontinence
Recommendations 28
(Conservative treatment of elderly people with
urinary incontinence)
GR
Do not treat asymptomatic bacteriuria in elderly
patients to improve urinary incontinence.
B
Support other healthcare professionals in use of
rehabilitation programmes, including prompted
voiding for the care of elderly care-dependent people
with urinary incontinence.
A
For adults with urinary incontinence, treat co-existing
constipation.
C
Offer pelvic floor muscle training to elderly women
with urinary incontinence.
B
Recommendations 29
(Antimuscarinic drugs)
GR
Offer immediate release or extended release formula-
tions of antimuscarinic drugs as initial drug therapy
for adults with urge urinary incontinence.
A
If immediate release formulations of antimuscarinic
drugs are unsuccessful for adults with urge urinary
incontinence, offer extended release formulations or
longer-acting antimuscarinic agents.
A
Consider using transdermal oxybutynin if oral
antimuscarinic agents cannot be tolerated due to dry
mouth.
B
192 Urinary Incontinence
Offer and encourage early review (of efficacy and side
effects) of patients on antimuscarinic medication for
urge urinary incontinence (< 30 days).
A
When prescribing antimuscarinic drugs to elderly
patients, be aware of the risk of cognitive side effects,
especially in those receiving cholinesterase inhibitors.
C
Avoid using oxybutynin immediate release in patients
who are at risk of cognitive dysfunction.
A
Consider use of trospium chloride in patients known
to have cognitive dysfunction.
B
Use solifenacin, tolterodine and darifenacin with cau-
tion in patients with cognitive dysfunction.
B
Do an objective assessment of mental function before
treating patients whose cognitive function may be at
risk.
C
Check mental function in patients on antimuscarinic
medication if they are at risk of cognitive dysfunction.
C
Recommendation 30
(Surgery for urinary incontinence in the elderly)
GR
Inform older women with stress urinary incontinence
about the increased risks associated with surgery,
including the lower probability of success.
B
This short text is based on the more comprehensive EAU guidelines
(ISBN 978-90-79754-71-7), available to all members of the European
Association of Urology at their website, http://www.uroweb.org.
193 Urinary Incontinence
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continued on page 194
194 Urinary Incontinence
M
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continued on page 195
195 Urinary Incontinence
M
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196 Urinary Incontinence
I
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continued on page 197
197 Urinary Incontinence
continued on page 198
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198 Urinary Incontinence
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199 Urological Infections
GUIDELINES ON
UROLOGICAL INFECTIONS
(Text update April 2010)
M. Grabe (chairman), T.E. Bjerklund-Johansen, H. Botto, M. ek,
K.G. Naber, R.S. Pickard, P. Tenke, F. Wagenlehner, B. Wullt
Introduction
Infections of the urinary tract (UTIs) pose a serious health
problem for patients at high cost for society. UTIs are also the
most frequent healthcare associated infections.
E. coli is the predominating pathogen in uncomplicated
UTIs while other Enterobacteriaceae and Enterococcus spp
are isolated in higher frequency in patients with urological
diseases. The present state of microbial resistance
development is alarming and the rates of resistance are
related to the amount of antibiotics used in the different
countries. Particularly worrisome is the increasing resistance
to broad spectrum antibiotics. It is thus essential to limit
the use of antibiotics in general and fluoroquinolones and
cephalosporins in particular, especially in uncomplicated
infections and asymptomatic bacteriuria.
Classification and definitions
For practical clinical reasons, UTIs and male genital tract
infections are classified into entities defined by the predomi-
nant clinical symptoms (Table 1).
200 Urological Infections
Table 1: Classification of urinary and male genital tract
infections
Uncomplicated lower UTI (cystitis)
Uncomplicated pyelonephritis
Complicated UTI with or without pyelonephritis
Urosepsis
Urethritis
Prostatitis, epididymitis, orchitis
The definitions of bacteriuria and pyuria are listed in Table 2.
Table 2: Significant bacteriuria in adults
1. 10
3
uropathogens/mL of midstream urine in acute
uncomplicated cystitis in female.
2. 10
4
uropathogens/mL of midstream urine in acute
uncomplicated pyelonephritis in female.
3. 10
5
uropathogens/mL in midstream urine of women or
10
4
uropathogens/mL of midstream urine in men (or in
straight catheter urine in women) with complicated UTI.
4. In a suprapubic bladder puncture specimen, any count of
bacteria is relevant.
Asymptomatic bacteriuria
Asymptomatic bacteriuria is defined as two positive urine
cultures taken more than 24 hours apart containing 10
5
uropathogens/mL of the same bacterial strain (usually only
the species can be detected).
Pyuria
The diagnostic requirement for pyuria is 10 white blood cells
per high-power field (HPF) (x400) in the resuspended sedi-
ment of a centrifuged aliquot of urine or per mm
3
in unspun
urine. For routine investigation, a dipstick method can also be
201 Urological Infections
used, including a leukocyte esterase test and the assessment
of haemoglobin and of nitrites.
Urethritis
Symptomatic urethritis is characterised by alguria and puru-
lent discharge.
Classification of prostatitis/chronic pelvic pain syndrome
(CPPS)
It is recommended that the classification according to
NIDDK/NIH is used (Table 3).
Table 3: Classification of prostatitis according to NIDDK/
NIH
I Acute bacterial prostatitis (ABP)
II Chronic bacterial prostatitis (CBP)
III Chronic pelvic pain syndrome (CPPS)
IIIA Inflammatory CPPS: WBC in EPS/voided
bladder urine-3 (VB3)/semen
IIIB Non-inflammatory CPPS: no WBC/EPS/VB3/semen
IV Asymptomatic inflammatory prostatitis (histological
prostatitis)
Epididymitis, orchitis
Most cases of epididymitis, with or without orchitis, are
caused by common urinary pathogens. Bladder outlet
obstruction and urogenital malformations are risk factors for
this type of infection. Consider Chlamydia trachomatis infec-
tion in the younger male population.
Diagnosis
UTI (general)
A disease history, physical examination and dipstick urinaly-
sis, including white and red blood cells and nitrite reaction,
202 Urological Infections
Table 4: Recommendations for antimicrobial therapy in urology
Diagnosis Most frequent pathogen/species Initial, empirical antimicrobial therapy Therapy duration
Cystitis
acute,
uncomplicated
E. coli
Klebsiella
Proteus
Staphylococci
TMP-SMX
1
Nitrofurantoin
Fosfomycin trometamol
Pivmecillinam
Alternative:
Fluoroquinolone
2,3
3 days
(5-)7 days
1 day
(3-)5 days
(1-)3 days
Pyelonephritis
acute,
uncomplicated
E. coli
Proteus
Klebsiella
Other enterobacteria
Staphylococci
Fluoroquinolone
2
Cephalosporin (group 3a)
Alternatives:
Aminopenicillin/BLI
Aminoglycoside
7-10 days
UTI with
complicating
factors
E. coli
Enterococci
Pseudomonas
Staphylococci
Fluoroquinolone
2
Aminopenicillin/BLI
Cephalosporin (group 2)
Cephalosporin (group 3a)
Aminoglycoside
3-5 days after
defervescence
or control/
elimination of
complicating
factor
Nosocomial UTI Klebsiella
Proteus In case of failure of initial therapy
within 1-3 days or in clinically
cases:
Anti-Pseudomonas active:
Fluoroquinolone, if not used initially
Acylaminopenicillin/BLI
Cephalosporin (group 3b)
Carbapenem
Aminoglycoside
In case of Candida:
Fluconazole
Amphotericin B
Pyelonephritis
severe
acute,
complicated
Enterobacter
Other enterobacteria
(Candida)
203 Urological Infections
Table 4: Recommendations for antimicrobial therapy in urology
Diagnosis Most frequent pathogen/species Initial, empirical antimicrobial therapy Therapy duration
Cystitis
acute,
uncomplicated
E. coli
Klebsiella
Proteus
Staphylococci
TMP-SMX
1
Nitrofurantoin
Fosfomycin trometamol
Pivmecillinam
Alternative:
Fluoroquinolone
2,3
3 days
(5-)7 days
1 day
(3-)5 days
(1-)3 days
Pyelonephritis
acute,
uncomplicated
E. coli
Proteus
Klebsiella
Other enterobacteria
Staphylococci
Fluoroquinolone
2
Cephalosporin (group 3a)
Alternatives:
Aminopenicillin/BLI
Aminoglycoside
7-10 days
UTI with
complicating
factors
E. coli
Enterococci
Pseudomonas
Staphylococci
Fluoroquinolone
2
Aminopenicillin/BLI
Cephalosporin (group 2)
Cephalosporin (group 3a)
Aminoglycoside
3-5 days after
defervescence
or control/
elimination of
complicating
factor
Nosocomial UTI Klebsiella
Proteus In case of failure of initial therapy
within 1-3 days or in clinically
cases:
Anti-Pseudomonas active:
Fluoroquinolone, if not used initially
Acylaminopenicillin/BLI
Cephalosporin (group 3b)
Carbapenem
Aminoglycoside
In case of Candida:
Fluconazole
Amphotericin B
Pyelonephritis
severe
acute,
complicated
Enterobacter
Other enterobacteria
(Candida)
204 Urological Infections
is re commended for routine diagnosis. Except in isolated
episodes of uncomplicated lower UTI (cystitis) in premeno-
pausal, healthy women, a urine culture is recommended in all
other types of UTI before treatment, so allowing antimicrobial
therapy to be adjusted if necessary.
Pyelonephritis
In cases of suspected pyelonephritis, it may be necessary to
evaluate the upper urinary tract to rule out upper urinary tract
obstruction or stone disease.
BLI = beta-lactamase inhibitor; UTI = urinary tract infection.
Prostatitis
acute, chronic
E. coli
Other enterobacteria
Pseudomonas
Enterococci
Chronic:
Staphylococci
Chlamydia
Ureaplasma
E. coli
Other enterobacteria
After urological
interventions - multi-
resistant pathogens:
Pseudomonas
Proteus
Serratia
Enterobacter
Fluoroquinolone
2
Alternative in acute bacterial
prostatitis:
Cephalosporin (group 3a/b)
In case of Chlamydia or Ureaplasma:
Doxycycline
Macrolide
Cephalosporin (group 3a/b)
Fluoroquinolone
2
Anti-Pseudomonas active
acylaminopenicillin/BLI
Carbapenem
Aminoglycoside
Acute:
2-4 weeks
Chronic:
4-6 weeks or
longer
3-5 days after
defervescence or
control/
elimination
of complicating
factor
Epididymitis
Ureaplasma:
Acute
Urosepsis
1
Only in areas with resistance rate < 20% (for E. coli).
2
Fluoroquinolone with mainly renal excretion (see text).
3
Avoid Fluoroquinolones in uncomplicated cystitis whenever possible.
205 Urological Infections
Urethritis
Pyogenic urethritis is indicated by a Gram stain of secretion
or urethral smear that shows more than five leukocytes per
HPF (x1,000) and in case of gonorrhoea gonococci are located
intracellularly as Gram-negative diplococci. A positive leuko-
cyte esterase test or more than 10 leukocytes per HPF (x400)
in the first voiding urine specimen is diagnostic.
Prostatitis/CPPS
In patients with prostatitis-like symptoms, an attempt should
be made to differentiate between bacterial prostatitis and
CPPS. This is best done by the four glass test according to
Mearse & Stamey, if acute UTI and STD can be ruled out.
Prostatitis
acute, chronic
E. coli
Other enterobacteria
Pseudomonas
Enterococci
Chronic:
Staphylococci
Chlamydia
Ureaplasma
E. coli
Other enterobacteria
After urological
interventions - multi-
resistant pathogens:
Pseudomonas
Proteus
Serratia
Enterobacter
Fluoroquinolone
2
Alternative in acute bacterial
prostatitis:
Cephalosporin (group 3a/b)
In case of Chlamydia or Ureaplasma:
Doxycycline
Macrolide
Cephalosporin (group 3a/b)
Fluoroquinolone
2
Anti-Pseudomonas active
acylaminopenicillin/BLI
Carbapenem
Aminoglycoside
Acute:
2-4 weeks
Chronic:
4-6 weeks or
longer
3-5 days after
defervescence or
control/
elimination
of complicating
factor
Epididymitis
Ureaplasma:
Acute
Urosepsis
1
Only in areas with resistance rate < 20% (for E. coli).
2
Fluoroquinolone with mainly renal excretion (see text).
3
Avoid Fluoroquinolones in uncomplicated cystitis whenever possible.
206 Urological Infections
Treatment and Prophylaxis
Treatment of UTI depends on a variety of factors. Table 4 pro-
vides an overview of the most common pathogens, antimicro-
bial agents and duration of treatment for different conditions.
Prophylactic treatment may be recommended for patients
with recurrent UTI. The regimens shown in Table 5 have a
documented effect in preventing recurrent UTI in women.
Special situations
UTI in pregnancy
Asymptomatic bacteriuria is treated with a 7-day course
based on sensitivity testing. For recurrent infections (sympto-
matic or asymptomatic), either cephalexin, 125-250 mg/day, or
nitrofurantoin, 50 mg/day, may be used for prophylaxis.
UTI in postmenopausal women
In women with recurrent infection, intravaginal oestriol is rec-
ommended. If this is not effective, antibiotic prophylaxis could
be considered.
UTI in children
Treatment periods should be extended to 7-10 days. Tetra-
cyclines and fluoroquinolones should not be used because of
adverse effects on teeth and cartilage.
Acute uncomplicated UTI in young men
Treatment should last at least 7 days.
Complicated UTI due to urological disorders
The underlying disorder must be managed if a permanent
cure is to be achieved. Whenever possible, treatment should
be guided by urine culture to avoid inducing resistant strains.
Sepsis in urology (urosepsis)
Patients with UTI may develop sepsis. Early signs of systemic
207 Urological Infections
inflammatory response (fever or hypothermia, tachycardia,
tachypnoea, hypotension, oliguria, leukopenia) should be
recognised as the first signs of possible multi-organ failure. As
well as appropriate antibiotic therapy, life-support therapy in
collaboration with an intensive care specialist may be
necessary. Any obstruction in the urinary tract must be
drained.
Table 5: Recommendations for antimicrobial prophylaxis of
recurrent uncomplicated UTI
Agent
1
Dose
Standard regimen
Nitrofurantoin 50 mg/day
Nitrofurantoin macrocrystals 100 mg/day
TMP-SMX 40/200 mg/day or
three times weekly
TMP 100 mg/day
Fosfomycin trometamol 3 g/10 day
Breakthrough infections
Ciprofloxacin 125 mg/day
Norfloxacin 200-400 mg/day
Pefloxacin 800 mg/week
During pregnancy
Cephalexin 125 mg/day
Cefaclor 250 mg/day
1
Taken at bedtime.
TMP = trimethoprim-sulphamethoxazole.
208 Urological Infections
Follow-up of patients with UTI
For routine follow-up after uncomplicated UTI and
pyelonephritis in women, dipstick urinanalysis is sufficient.
In women with a recurrence of UTI within 2 weeks, repeat-
ed urinary culture with antimicrobial testing and urinary
tract evaluation is recommended.
In the elderly, newly developed recurrent UTI may warrant
a full evaluation of the urinary tract.
In men with UTI, an urological evaluation should be per-
formed in adolescent patients, cases of recurrent infec-
tion and all cases of pyelonephritis. This recommendation
should also be followed in patients with prostatitis, epidi-
dymitis and orchitis.
In children, investigations are indicated after two episodes
of UTI in girls and one episode in boys. Recommended
investigations are ultrasonography of the urinary tract sup-
plemented by voiding cystourethrography.
Urethritis
The following guidelines for therapy comply with the recom-
mendations of the Center for Disease Control and Prevention
(2002). For the treatment of gonorrhoea, the following antimi-
crobials can be recommended:
First choice Second choice
Cefixime 400 mg orally Ciprofloxacin 500 mg orally or
as a single dose Ofloxacin 400 mg orally or
Ceftriaxone 1g im Levofloxacin 250 mg orally
as a single dose as a single dose
(im with local anaesthetic)
As gonorrhoea is often accompanied by chlamydial infec-
tion, an antichlamydial active therapy should be added.
The following treatment has been successfully applied in
Chlamydia trachomatis infections:
209 Urological Infections
First choice Second choice
Azithromycin Erythromycin
1 g (= 4 caps @ 250 mg) 4 times daily 500 mg
orally as single dose orally for 7 days
Doxycycline Ofloxacin 2 times daily
2 times daily 100 mg orally 300 mg orally or
for 7 days Levofloxacin once daily
500 mg orally
for 7 days
If therapy fails, infections with Trichomonas vaginalis and/or
Mycoplasma spp. should be considered. These can be treated
with a combination of metronidazole (2 g orally as a single
dose) and erythromycin (500 mg orally, 4 times daily, for 7
days).
Prostatitis
Acute bacterial prostatitis can be a serious infection. The
parenteral administration of high doses of bactericidal antibi-
otics, such as an aminoglycoside and a penicillin derivative or
a third-generation cephalosporin, is required until deferves-
cence occurs and infection parameters return to normal. In
less severe cases, a fluoroquinolone may be given orally for at
least 10 days.
In chronic bacterial prostatitis and inflammatory CPPS, a
fluoroquinolone or trimethoprim should be given orally for 2
weeks after the initial diagnosis. The patient should then be
reassessed and antibiotics only continued if the pretreatment
cultures were positive or if the patient has reported positive
effects from the treatment. A total treatment period of 4-6
weeks is recommended.
Combination therapy with antibiotics and -blockers:
Urodynamic studies have shown increased urethral closing
pressure in patients with chronic prostatitis. Combination
210 Urological Infections
Table 6: Recommendations for peri-operative antibacterial prophylaxis in urology
Procedure Pathogens Prophylaxis Antibiotics Remarks
(expected) (standard)
Diagnostic procedures
Transrectal biopsy of the Enterobacteriaceae All patients Fluoroquinolones Single dose effective in low
prostate (Anaerobes) TMP SMX risk. Consider prolonged
Metronidazole
1
course in risk patients
Cystoscopy Enterobacteriaceae No TMP SMX Consider in risk patients
Urodynamic study Enterococci Cephalosporin 2
nd

Staphylococci generation
Ureteroscopy Enterobacteriaceae No TMP SMX

No studies
Enterococci Cephalosporin 2
nd

Staphylococci generation
Endourological surgery and SWL
SWL Enterobacteriaceae No TMP SMX In patients with stent or
Enterococci Cephalosporin 2
nd
or nephrostomy tube or other
3
rd
generation risk factor
Aminopenicillin/BLI
2
Ureteroscopy for Enterobacteriaceae No TMP SMX Consider in risk patients
uncomplicated distal stone Enterococci Cephalosporin 2
nd
or
Staphylococci 3
rd
generation
Aminopenicillin/BLI
Fluoroquinolones
Ureteroscopy of proximal Enterobacteriaceae All patients TMP SMX Short course,
or impacted stone and Enterococci Cephalosporin 2
nd
or Length to be determined
percutaneous stone Staphylococci 3
rd
generation Intravenous suggested at
extraction Aminopenicillin/BLI operation
Fluoroquinolones
TUR of the prostate Enterobacteriaceae All patients TMP SMX Low-risk patients and
Enterococci Cephalosporin 2
nd
or small-size prostate
3
rd
generation require no prophylaxis
Aminopenicillin/BLI
211 Urological Infections
Table 6: Recommendations for peri-operative antibacterial prophylaxis in urology
Procedure Pathogens Prophylaxis Antibiotics Remarks
(expected) (standard)
Diagnostic procedures
Transrectal biopsy of the Enterobacteriaceae All patients Fluoroquinolones Single dose effective in low
prostate (Anaerobes) TMP SMX risk. Consider prolonged
Metronidazole
1
course in risk patients
Cystoscopy Enterobacteriaceae No TMP SMX Consider in risk patients
Urodynamic study Enterococci Cephalosporin 2
nd

Staphylococci generation
Ureteroscopy Enterobacteriaceae No TMP SMX

No studies
Enterococci Cephalosporin 2
nd

Staphylococci generation
Endourological surgery and SWL
SWL Enterobacteriaceae No TMP SMX In patients with stent or
Enterococci Cephalosporin 2
nd
or nephrostomy tube or other
3
rd
generation risk factor
Aminopenicillin/BLI
2
Ureteroscopy for Enterobacteriaceae No TMP SMX Consider in risk patients
uncomplicated distal stone Enterococci Cephalosporin 2
nd
or
Staphylococci 3
rd
generation
Aminopenicillin/BLI
Fluoroquinolones
Ureteroscopy of proximal Enterobacteriaceae All patients TMP SMX Short course,
or impacted stone and Enterococci Cephalosporin 2
nd
or Length to be determined
percutaneous stone Staphylococci 3
rd
generation Intravenous suggested at
extraction Aminopenicillin/BLI operation
Fluoroquinolones
TUR of the prostate Enterobacteriaceae All patients TMP SMX Low-risk patients and
Enterococci Cephalosporin 2
nd
or small-size prostate
3
rd
generation require no prophylaxis
Aminopenicillin/BLI
212 Urological Infections
TUR of bladder tumour Enterobacteriaceae No TMP SMX Consider in risk patients
Enterococci Cephalosporin 2
nd
or and large tumours
3
rd
generation
Aminopenicillin/BLI
Open or laparoscopic urological surgery
3
Clean operations Skin-related No Consider in high-risk
pathogens, patients.
e.g. staphylococci Short post-operative
Catheter- catheter requires no
associated treatment
uropathogens
Clean-contaminated Enterobacteriaceae Recommended TMP SMX Single peri-operative
(opening of urinary tract) Enterococci Cephalosporin 2
nd
or course
Staphylococci 3
rd
generation
Aminopenicillin/BLI
Clean-contaminated/ Enterobacteriaceae All patients Cephalosporin 2
nd
or As for colonic surgery
contaminated (use of bowel Enterococci 3
rd
generation
segments): Anaerobes Metronidazole
Skin-related
bacteria
Implant of prosthetic Skin-related All patients Cephalosporin 2
nd
or
devices bacteria, 3
rd
generation
e.g. staphylococci Penicillin
(penicillinase stable)
BLI = beta-lactamase inhibitor; TMP SMX = trimethoprim with or without sulphamethoxale (co-trimoxazole); TUR = transurethral
resection.
1
No evidence for the use of mettronidazole in prostate core biopsies.
2
Gram-negative bacteria excluding Pseudomonas aeruginosa.
3
Classifications of surgical field contamination (CDC).
213 Urological Infections
TUR of bladder tumour Enterobacteriaceae No TMP SMX Consider in risk patients
Enterococci Cephalosporin 2
nd
or and large tumours
3
rd
generation
Aminopenicillin/BLI
Open or laparoscopic urological surgery
3
Clean operations Skin-related No Consider in high-risk
pathogens, patients.
e.g. staphylococci Short post-operative
Catheter- catheter requires no
associated treatment
uropathogens
Clean-contaminated Enterobacteriaceae Recommended TMP SMX Single peri-operative
(opening of urinary tract) Enterococci Cephalosporin 2
nd
or course
Staphylococci 3
rd
generation
Aminopenicillin/BLI
Clean-contaminated/ Enterobacteriaceae All patients Cephalosporin 2
nd
or As for colonic surgery
contaminated (use of bowel Enterococci 3
rd
generation
segments): Anaerobes Metronidazole
Skin-related
bacteria
Implant of prosthetic Skin-related All patients Cephalosporin 2
nd
or
devices bacteria, 3
rd
generation
e.g. staphylococci Penicillin
(penicillinase stable)
BLI = beta-lactamase inhibitor; TMP SMX = trimethoprim with or without sulphamethoxale (co-trimoxazole); TUR = transurethral
resection.
1
No evidence for the use of mettronidazole in prostate core biopsies.
2
Gram-negative bacteria excluding Pseudomonas aeruginosa.
3
Classifications of surgical field contamination (CDC).
214 Urological Infections
treatment with -blockers and antibiotics has been reported
to have a higher cure rate than antibiotics alone in inflammato-
ry CPPS. This treatment option is favoured by many urologists.
Surgery
Generally, surgery should be avoided in the treatment of pros-
tatitis, except for the drainage of prostatic abscesses.
Epididymitis, orchitis
Prior to antimicrobial therapy, a urethral swab and midstream
urine sample should be obtained for microbiological investi-
gation. The first choice of drug therapy should be fluoroqui-
nolones, preferably those agents that react well against C.
trachomatis (e.g. ofloxacin, levofloxacin), because of their
broad antibacterial spectra and favourable penetration into
urogenital tract tissues.
In cases caused by C. trachomatis, treatment may also be
continued with doxycycline, 200 mg/day, for a total treatment
period of at least 2 weeks. Macrolides are alternative agents.
In cases of C. trachomatis infection, the sexual partner should
also be treated.
Perioperative antibacterial prophylaxis in urological
surgery
The main aim of antimicrobial prophylaxis in urology is to pre-
vent symptomatic or febrile genitourinary infections, such as
acute pyelonephritis, prostatitis, epididymitis and urosepsis,
as well as serious wound infections. The recommendations for
short-term peri-operative antibacterial prophylaxis in stand-
ard urological interventions are listed in table 6.
This short booklet is based on the more comprehensive EAU guide-
lines (ISBN 978-90-79754-70-0), available to all members of the
European Association of Urology at their website,
http://www.uroweb.org.
215 Neurogenic Lower Urinary Tract Dysfunction
GUIDELINES ON NEUROGENIC LOWER
URINARY TRACT DYSFUNCTION
(Text update March 2009)
J. Pannek (co-chair), B. Blok (co-chair), D. Castro-Diaz,
G. Del Popolo, G. Kramer, P. Radziszewski, A. Reitz, M. Sthrer,
J-J. Wyndaele
Eur Urol 2009 Jul;56(1):81-8
Introduction
Before the 1980s, considerable morbidity was associated with
renal failure in patients with neurogenic lower urinary tract
dysfunction (NLUTD). Most patients with NLUTD require life-
long care to maintain their quality of life (QoL) and maximise
life-expectancy. Significant technological developments that
have occurred over the last 30 years have helped to achieve
these goals.
Terminology
The terminology used and the diagnostic procedures outlined
follow the recommendations for the investigation of the lower
urinary tract (LUT) published by the International Continence
Society (ICS).
Risk factors and epidemiology
All central and peripheral neurological disorders carry a high
risk of causing functional disturbances of the urinary tract.
Classification
Several classification systems have been proposed for NLUTD.
The panel recommends a functional classification for motor
function based on urodynamic and clinical findings (Figure 1).
216 Neurogenic Lower Urinary Tract Dysfunction
Fig. 1: The EAU-Madersbacher classification system
Detrusor
Over- Over- Over- Under-
active active active active
Overactive Underactive Normo-active Overactive
Urethral sphincter
Detrusor
Under- Under- Normo- Normo-
active active active active

Underactive Normo-active Overactive Underactive
Urethral sphincter
Adapted from Madersbacher et al.
Timing of diagnosis and treatment
In both congenital and acquired NLUTD, early diagnosis and
treatment are essential, as irreversible changes within the
LUT may occur, even when the related neuropathological
signs are normal. Also, remember that NLUTD can, by itself,
be the presenting feature of neurological pathology.
Diagnosis
Patient assessment
Diagnosis of NLUTD should be based on a comprehensive
assessment of neurological and non-neurological conditions.
217 Neurogenic Lower Urinary Tract Dysfunction
Initial assessment should include a detailed history, physical
examination, and urinalysis.
History
An extensive general and specific history is mandatory and
should concentrate on past and present symptoms and dis-
orders of the urinary tract, bowel, and sexual and neurological
function. Special attention should be paid to possible warning
signs and symptoms (e.g. pain, infection, haematuria, fever)
that warrant further investigation.
Physical examination
The neurological status should be described as completely
as possible. All sensations and reflexes in the urogenital area
must be tested, including detailed testing of the anal sphinc-
ter and pelvic floor functions (Figure 2). Availability of this
clinical information is essential for the reliable interpretation
of subsequent diagnostic investigations.
218 Neurogenic Lower Urinary Tract Dysfunction
Fig. 2: The neurological status of a patient with NLUTD must
be described as completely as possible
(a - dermatomes, b - associated reflexes)

Fig. 2a - Dermatomes of spinal cord levels L2-S4.
Fig. 2b - Urogenital and other reflexes in lower spinal cord.
219 Neurogenic Lower Urinary Tract Dysfunction
Urodynamic tests
A bladder diary should be recorded for at least 2-3 days.
Uroflowmetry and US assessment of post-void residual should
be repeated at least 2 or 3 times in patients able to void.
Invasive urodynamic studies comprise mandatory assess-
ment tools to determine the exact type of NLUTD (Table 1).
Table 1: Guidelines for urodynamics and
uro-neurophysiology tests in NLUTD GR
Urodynamic investigation is necessary to document
the (dys-)function of the LUT.
A
The recording of a bladder diary is advisable. B
Non-invasive testing is mandatory before invasive
urodynamics is planned.
A
Video-urodynamics is currently the preferred method
for invasive urodynamics in patients with NLUTD. If
this is not available, then a filling cystometry continu-
ing into a pressure flow study should be performed.
A
For standard urodynamic testing, a physiological filling
rate (see Table 1, e.g. not faster than 20 mL/min) and
body-warm fluid must be used.
A
Specific uro-neurophysiological tests and provocative
manoeuvres (e.g. fast filling cystometry with cooled
saline [the ice water test], coughing, tapping, anal
stretch) are elective procedures.
C
Filling cystometry is the only procedure that quantifies the
filling function of the bladder. However, when filling
cystometry is used alone, the results have limited signifi-
cance.
Measurement of detrusor leak point pressure (DLPP) has
limited diagnostic value; it is not recommended as a stand
alone test.
220 Neurogenic Lower Urinary Tract Dysfunction
Pressure flow studies: the function of the LUT must also be
recorded during the voiding phase.
Video-urodynamics combines filling cystometry and pressure
flow studies with radiological imaging. Currently, video-uro-
dynamics is considered to provide the most comprehensive
information evaluating NLUTD.
Electromyography (EMG) is a semi-quantitative measure of
pelvic floor activity, which can be used to detect detrusor/
sphincter dyssynergia (DSD) and pelvic floor relaxation dis-
orders.
Table 2: Characteristic findings in NLUTD*
Filling phase
Increased, decreased, or absent bladder sensation
Vegetative non-specific sensations
Low bladder compliance
High capacity bladder
Detrusor overactivity, spontaneous or provoked
Incompetent urethral closure mechanism
Voiding phase
Acontractile or underactive detrusor
Bladder outlet obstruction
DSD
Non-relaxing urethral sphincter obstruction
These signs warrant further neurological evaluation, as
LUTD may be the presenting symptom of a neurological
disease.
*modified from ICS publication.
Treatment
Introduction
Treatment of NLUTD aims to protect the upper urinary tract,
221 Neurogenic Lower Urinary Tract Dysfunction
and improve continence, QoL and, whenever possible, LUT
function.
In patients with a high detrusor pressure in the filling
phase, the principal aim of treatment is conversion of an
overactive, high-pressure bladder into a low-pressure reser-
voir; even if this should result in a high post-void residual. The
patients QoL is a prime consideration when making any treat-
ment decision.
Conservative treatment
Drug treatment for neurogenic detrusor overactivity (NDO)
Antimuscarinic agents are currently the most widely used
treatment, although most of the available drugs have not
been registered for the treatment of this patient population.
Antimuscarinic agents can also be given intravesically.
Drug treatment for neurogenic detrusor underactivity
There is no evidence of effective drug treatment for detrusor
underactivity.
Drug treatment to decrease bladder outlet resistance
Selective and non-selective alpha-blockers have been partial-
ly successful in decreasing bladder outlet resistance, residual
urine and autonomic dysreflexia.
Catheterisation
Intermittent, self- or third-party, catheterisation (IC) is the
gold standard for the management of NLUTD. Compared to
clean IC, aseptic IC provides significant benefit in reducing
the potential for contamination.
On average, IC, using a 12-14 Fr catheter, is needed 4-6
times per day.
Indwelling transurethral IC and, to a lesser extent, suprapubic
cystostomy should be avoided as they are risk factors for UTI
222 Neurogenic Lower Urinary Tract Dysfunction
and significant long-term complications. If indwelling ca-
theters must be used, empirical evidence and expert opinion
suggests silicone catheters provide advantages over latex
catheters.
Assisted bladder emptying
Triggered reflex voiding is not recommended as there is a risk
of pathologically elevated bladder pressures. Only in the case
of absence, or surgically reduced, outlet obstruction it may be
an option.
Bladder compression techniques to expel urine (Crede)
and voiding by abdominal straining (Valsalva manoeuvre) cre-
ate high pressures and are potentially hazardous, and their
use should be discouraged.
Rehabilitation
In selected patients, pelvic floor muscle exercises, pelvic floor
electro-stimulation, and biofeedback might be beneficial.
External appliances
Social continence for the incontinent patient can be achieved
using an appropriate method of urine collection.
Minimally invasive treatment
Botulinum toxin A injections in the bladder
Botulinum toxin A causes a long-lasting (approximately
9 months), reversible, chemical denervation.
Intravesical vanilloid treatment
Resiniferatoxin and capsaicin have limited clinical efficacy
compared to botulinum toxin A injected in the detrusor.
Bladder neck and urethral procedures
Reduction of the bladder outlet resistance, to protect the
upper urinary tract, can be achieved by sphincterotomy
223 Neurogenic Lower Urinary Tract Dysfunction
or chemical denervation of the sphincter using botulinum
toxin A. Insertion of urethral stents is not recommended.
Increasing bladder outlet resistance using bulking agents or
urethral inserts, or alternative appliances is not recommend-
ed for long-term treatment.
NDO and reflux
Vesico-ureteral reflux should be managed by lowering intra-
vesical pressure. If reflux is persistent, intervention using bul-
king agents or ureteral re-implantation can be considered.
Surgical treatment
Overactive detrusor
Bladder augmentation/clam cystoplasty is indicated for an
overactive detrusor, when less invasive procedures have
failed. Alternative options include: auto-augmentation (myo-
mectomy), dorsal rhizotomy, with or without sacral anterior
root stimulation (SARS) (complete lesions), and neuromodula-
tion (incomplete lesions). Substitution, with either continent
or incontinent diversion, is indicated for the small contracted
non-compliant bladder.
Fig. 3: Surgery for neurogenic detrusor overactivity
Surgery for neurogenic detrusor overactivity
All lesions
Botulinum Toxin A Neuromodulation Deaerentation
Auto-Augmentation (optional)
Clam Cystoplasty
Enterocystoplasty
Neurostimulation
Complete lesion Incomplete lesion
224 Neurogenic Lower Urinary Tract Dysfunction
Underactive detrusor
Sacral anterior root stimulation (complete lesions) and sacral
neuromodulation (incomplete lesions) are effective in selec-
ted patients.
Sphincter insufficiency (underactive urethra)
The artificial urinary sphincter is the preferred tried and
tested treatment.
Procedures to treat sphincter incompetence are suitable
only when the detrusor activity is, or can be, controlled and
there is no significant associated vesico-ureteral reflux.
Quality of life
Quality of life (QoL) represents a very important aspect in
the global management of the patient who has NLUTD.
Restoration and maintenance of the patients QoL it as much
as possible, should be one of the major aims of treatment.
QoL should be integral to the evaluation of lower urinary tract
symptoms in patients with NLUTD and also, when considering
any type of treatment for neurogenic bladder dysfunction.
Follow-up
Meticulous follow-up and regular checks are essential.
Individualised patient follow-up is imperative to safeguard
QoL and life expectancy. The underlying pathology and the
state of the urinary tract dictate the frequency of follow-up
required.
225 Neurogenic Lower Urinary Tract Dysfunction
Table 3: Minimum follow-up required in patients with
NLUTD*
Investigation Frequency GR
Urinalysis At least once every 6
months
A
US of the upper urinary tract,
bladder status, post void
residual
Every 6 months A
Physical examination, blood
biochemistry, and urine micro-
biology
Annually A
(Video-)urodynamic investi-
gations in patients without
detrusor overactivity and with
normal bladder compliance
Every 2 years A
(Video-)urodynamic investiga-
tions in patients with detrusor
overactivity, and/or low blad-
der compliance
At least once a year A
The need for detailed special investigations must be deter-
mined on the basis of the patients risk profile (see above),
but should, where indicated, include a video-urodynamic
study, which should be carried out in an institution with
neuro-urological expertise.
* Grades of recommendation assigned on basis of panel con-
sensus.
Summary
NLUTD is a multi-faceted pathology. Extensive investigation
and a precise diagnosis are required before the clinician can
initiate individualised therapy. Treatment must take into
account the patients medical and physical condition and
expectations with regard to his/her future social, physical, and
medical situation.
226 Neurogenic Lower Urinary Tract Dysfunction
This short booklet text is based on the more comprehensive EAU
guidelines (ISBN 978-90-79754-09-0), available to all members of the
European Association of Urology at their website,
http://www.uroweb.org.
227 Urological Trauma
GUIDELINES ON
UROLOGICAL TRAUMA
(Text update March 2013)
D.J. Summerton (chair), N. Djakovic, N.D. Kitrey, F.E. Kuehhas,
N. Lumen, E. Serafetinides
Eur Urol 2010 May;57(5):791-803
Eur Urol 2012 Oct;62(4):628-39
Introduction
Genito-urinary trauma is seen in both sexes and in all age
groups, but is more common in males. Traumatic injuries are
classified according to the basic mechanism into penetrating
and blunt.
Penetrating trauma is further classified according to the
velocity of the projectile:
1. High-velocity projectiles (e.g. rifle bullets - 800-1000m/sec).
2. Medium-velocity (e.g. handgun bullets - 200-300 m/sec).
3. Low-velocity items (e.g. knife stab).
High-velocity weapons inflict greater damage because the
bullets transmit large amounts of energy to the tissues,
resulting in damage to a much larger area then the projectile
tract itself. In lower velocity injuries, the damage is usually
confined to the track of the projectile.
Blast injury is a complex cause of trauma because it
commonly includes both blunt and penetrating trauma, and
may also be accompanied by a burn injury.
Initial evaluation and treatment
The first priority is stabilisation of the patient and treatment
228 Urological Trauma
of associated life-threatening injuries. A direct history is
obtained from the patient (if conscious) or from witnesses/
emergency personnel (if patient unconscious and/or seriously
injured).
In penetrating injuries, assess size of the weapon in stab-
bings, and the type and caliber of the weapon used in gunshot
wounds. The medical history should be as detailed as pos-
sible.
It is important to recognise the high risk of hepatitis B and
C infection in trauma patients and take appropriate precau-
tions. In any penetrating trauma, tetanus vaccination should
be considered according to the patients vaccination history
and nature of the wound.
Renal Trauma
Renal injuries (RI) account for 1-5% of all trauma and in 10% of
all abdominal trauma cases.
Table 1: Injury severity scale for the kidney*
#
Grade Description
1 Contusion or non-expanding subcapsular
haematoma, no laceration
2 Non-expanding perirenal haematoma, cortical
laceration < 1 cm deep without extravasation
3 Cortical laceration > 1 cm without urinary
extravasation
4 Laceration: through corticomedullary junction
into collecting system or vascular: segmental renal
artery or vein injury with contained haematoma
5 Laceration: shattered kidney or vascular: renal
pedicle injury or avulsion
* Adapted from the American Association for the Surgery of
Trauma (AAST).
# Advance one grade for multiple injuries up to grade 3.
229 Urological Trauma
Diagnosis
Haemodynamic stability should be assessed upon
admission.
History: time and setting of incident, past renal surgery,
known renal abnormalities.
Lab: gross haematuria, dipstick urine analysis, serial hae-
matocrit, baseline serum creatinine.
In blunt trauma with macroscopic or microscopic
haematuria and hypotension, a history of rapid decelera-
tion injury and/or significant associated injuries should
undergo radiographic evaluation.
Any degree of haematuria after penetrating abdominal or
thoracic injury requires urgent imaging.
Imaging: computed tomography (CT) scan, with and with-
out intravenous contrast material, in haemodynamically
stable patients.
Ultrasound (US) may be helpful during the primary evalua-
tion or follow-up of recuperating patients.
Angiography can be used for diagnosis and simultaneous
selective embolization of bleeding vessels if necessary.
Treatment
Indications for renal exploration include:
haemodynamic instability;
exploration for associated injuries;
expanding or pulsatile peri-renal haematoma identified
during laparotomy.
grade 5 vascular injury (Figs. 1 and 2).
Interventional radiology is indicated in patients with active
bleeding from renal injury but without other indications for
immediate abdominal operation.
230 Urological Trauma
Fig. 1: Evaluation of blunt renal trauma in adults
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231 Urological Trauma
Fig. 2: Evaluation of penetrating renal trauma in adults
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232 Urological Trauma
Post-operative care, follow-up and complications
Repeat imaging is recommended in cases of suspected
complications, cases of fever, flank pain, or falling
haematocrit.
Nuclear scintigraphy is useful for documenting functional
recovery.
First follow up should be at approximately 3 months after
major renal injury with hospitalisation and should include:
physical examination, urinalysis, individualised radiologi-
cal investigation, blood pressure measurement and serum
determination of renal function.
Long-term follow-up should be decided on a case-by-case
basis.
Complications following renal trauma require a thorough
radiographic evaluation.
Medical management and minimally invasive techniques
should be the first choice for the management of compli-
cations.
Iatrogenic renal injuries (IRI)
IRIs are procedure-dependent (1.8-15%).
Significant injury requiring intervention is rare.
Most common injuries are vascular.
Renal allografts are more susceptible.
Injuries occurring during surgery are rectified immediately.
Symptoms suggestive of a significant injury require investi-
gation.
Patients with minor injuries should be treated conserva-
tively.
Severe or persistent injuries require intervention with
embolization.
In stable patients, a second embolisation should be
considered in case of failure.
233 Urological Trauma
Ureteral Trauma
Ureteral injuries are quite rare - most are iatrogenic. They
are often missed intra-operatively, usually involve the lower
ureter, and may result in severe sequelae. Risk factors include
advanced malignancy, prior surgery or irradiation - i.e. condi-
tions which alter the normal anatomy. External ureteral trau-
ma usually accompanies severe abdominal and pelvic injuries.
Gunshot wounds account for the majority of penetrating
ureteral trauma, while motor vehicle accidents account for
most of blunt injuries.
Diagnosis
A high index of suspicion of ureteral injury should be main-
tained because the majority of cases are diagnosed late
and predispose the patient to pain, infection, and renal
function impairment.
Haematuria is an unreliable indicator.
Extravasation of contrast material in CT is the hallmark
sign of ureteral trauma, and in unclear cases, a retrograde
or antegrade urography is required for confirmation.
Treatment
Partial injury can be managed with ureteral stenting or
urinary diversion by a nephrostomy.
In complete injuries, ureteral reconstruction following tem-
porary urinary diversion is required.
The type of repair procedure depends on the site of the
injury (table 1), and it should follow the principles outlined
in table 2.
Proximal and mid-ureteral injuries can often be managed
by primary uretero-ureterostomy, while a distal injury is
often treated with ureteral reimplantation.
234 Urological Trauma
Ureteral reconstruction options by site of injury
Site of injury Reconstruction options
Upper ureter Uretero-ureterostomy
Transuretero-ureterostomy
Uretero-calycostomy
Mid ureter Uretero-ureterostomy
Transuretero-ureterostomy
Ureteral reimplantation and a Boari flap
Lower ureter Ureteral reimplantation
Ureteral reimplantation with a psoas hitch
Complete Ileal interposition graft
Autotransplantation
Principles of surgical repair of ureteral injury
Debridement of necrotic tissue
Spatulation of ureteral ends
Watertight mucosa-to-mucosa anastomosis with absorb-
able sutures
Internal stenting
External drain
Isolation of injury with peritoneum or omentum
Bladder Trauma
Bladder injuries can be due to external (blunt or penetrating)
or iatrogenic trauma. Iatrogenic trauma is caused by external
laceration or internal perforation (mainly during TURB). Blunt
bladder injuries are strongly associated with pelvic fractures.
Bladder injuries are classified as extraperitoneal, intraperito-
neal or combined.
235 Urological Trauma
Diagnosis
Clinical signs and symptoms
External trauma
Cardinal sign: gross haematuria.
Others: abdominal tenderness, inability to void, bruises
over the suprapubic region, and abdominal distension (in
case of urinary ascites).
Penetrating bladder injury: entrance and exit wounds in
lower abdomen or perineum.
Bloody urethrorrhaphy: suspect concomitant urethral
injury.
Iatrogenic trauma
External perforation: extravasation of urine, visible lacera-
tion, clear fluid in the surgical field, appearance of the blad-
der catheter, and blood and/or gas (in case of laparoscopy)
in the urine bag.
Internal perforation: fatty tissue or bowel between detru-
sor muscle fibres, inability of bladder distension, low return
of irrigation fluid and/or abdominal distension.
Postoperative symptoms of unrecognised bladder per-
foration: haematuria, lower abdominal pain, abdominal
distension, ileus, peritonitis, sepsis, urine leakage from the
wound, decreased urinary output, and increased serum
creatinine.
Imaging
Cystography (conventional or CT-cystography)
Fill the bladder with at least 350 mL of dilute contrast
material.
CT cystography preferred in case of other possible abdomi-
nal injuries or causes of abdominal pain.
Standard evaluation for external trauma and in case of sus-
picion of an iatrogenic bladder injury in the postoperative
setting.
236 Urological Trauma
Imperative in case of gross haematuria combined with
pelvic fracture.
Cystoscopy
To detect intra-operative bladder injuries.
Recommended after minimally invasive synthetic sub-
urethral sling operations by retropubic route and major
gynaecologic operations.
Optional after any other type of sling procedure or trans-
vaginal mesh procedure.
Treatment
Surgical repair (two-layer vesicorraphy)
Penetrating injury.
Blunt intraperitoneal injury.
Blunt extraperitoneal injury with internal osteosynthetic
fixation of pelvic fracture.
(large) Iatrogenic internal intraperitoneal injury.
Intra-operative recognised injury.
In case of bladder neck involvement, bony fragment(s) in
the bladder, concomitant rectal injury and/or bladder wall
entrapment.
Conservative treatment (urinary catheter)
Postoperative recognised extraperitoneal perforation.
Blunt extraperitoneal perforation.
Iatrogenic internal extraperitoneal perforation.
Small internal intraperitoneal perforation in absence of
ileus and peritonitis. Placement of an intraperitoneal drain
is optional.
Urethral Trauma
Injuries to the anterior urethra (AU) are caused by trauma
during sexual intercourse (associated with penile fracture),
penetrating trauma, placement of penile constriction
237 Urological Trauma
bands, and from iatrogenic trauma e.g. endoscopic instru-
ments, catheterisation.
Injuries to the posterior urethra (PU) occur with pelvic
fractures, mostly as a result of motor vehicle accidents.
The male PU is injured in 4-19% of pelvic fractures, and the
female urethra in 0-6% of all pelvic fractures.
The combination of straddle fractures with diastasis of the
sacroiliac joint has the highest risk of urethral injury.
Injuries can vary from simple stretching to partial rupture
to complete disruptions.
Urethral injuries in women are rare.
Diagnosis
Blood at the external urethral meatus is the most common
clinical sign, and indicates the need for further diagnostic
work up.
Although non-specific, haematuria on a first voided speci-
men may indicate urethral injury. The amount of urethral
bleeding correlates poorly with the severity of injury.
Pain on urination or inability to void may indicate disrup-
tion.
Blood at the vaginal introitus is present in more than 80%
of female patients with pelvic fractures and co-existing
urethral injuries.
Rectal examination may reveal a high riding prostate.
However, this is an unreliable finding. Blood on the exami-
nation finger is suggestive of a rectal injury associated
with pelvic fracture Urethral bleeding or urinary extravasa-
tion can cause penile and scrotal swelling and hematoma.
Retrograde urethrography is the gold standard for evalua-
ting urethral injury and urethral catheterisation should be
avoided until the urethra is imaged.
In an unstable patient, however, an attempt can be made
to pass a urethral catheter (gently, by someone with uro-
238 Urological Trauma
logical experience). If this is not possible, a suprapubic
catheter is inserted and a retrograde urethrogram is per-
formed later.
In females, urethroscopy may be an important adjunct for
the identification and staging of urethral injuries
Treatment
While intervention should be guided by the clinical circum-
stances, the following treatment is suggested:
Anterior urethral injuries are treated by primary urethral
repair only if associated with penile fracture or in pen-
etrating wounds. Blunt trauma should be treated in the
acute management by suprapubic cystosomy or urethral
catheterisation. After the patient has recovered from any
associated injuries, and the urethral injury has stabilized,
delayed management is used applied 3 to 6 months. Short
and flimsy strictures are managed by optical urethrotomy
or urethral dilatation. Denser strictures require urethral
reconstruction.
Posterior urethral injuries are treated by primary open
repair only in stable patients with penetrating wounds. In
all other cases a suprapubic cystostomy is performed. In
stable patients with blunt trauma associated with com-
plete urethral rupture an open surgery is only necessary
in the acute phase when complicated by bladder neck or
rectal injuries. In all other cases a suprapubic cystostomy
is the appropriate acute management.
If delayed management is conducted, it consists of
endoscopic realignment or delayed urethroplasty.
Urethral strictures following partial ruptures can be
treated by optical urethrotomy.
Iatrogenic urethral trauma
Most commonly caused by urethral instrumentation, and
results in stricture formation.
239 Urological Trauma
Due to their variable location and severity, they often
require different management strategies.
Short and flimsy strictures can be treated by urethrotomy.
If the stricture is longer or denser, urethroplasty should be
considered.
Genital Trauma
Of all genito-urinary injuries, one-third to two-thirds involve
the external genitalia and is much more common in males
- due to anatomical differences and increased frequency
of road traffic accidents, physical sports, violent crime, and
war-fighting. 80% is blunt trauma, 20% is due to penetrating
injuries.
Diagnosis
Urinalysis should be performed.
Macro- and or microhaematuria require a retrograde
urethrogram in males, and consideration of cystoscopy in
females.
In women with genital injuries and blood at the vaginal
introitus, further gynaecologic investigation to exclude
vaginal injury.
In cases of suspected sexual abuse gynecological and
forensic support and advice is necessary and the emotio-
nal situation and privacy of the patient must be respected.
Blunt Penile trauma
Usually results from trauma to the erect penis during
sexual intercourse or masturbation.
Penile fracture
Sudden cracking or popping sound, pain and immediate
detumescence.
Local swelling of the penile shaft is seen and this may
extend to the lower abdominal wall.
240 Urological Trauma
The rupture of the tunica may be palpable.
Thorough history and examination confirms diagnosis
Imaging (US or magnetic resonance imaging [MRI]) may be
useful.
Treatment
Subcutaneous haematoma, without associated rupture of
the cavernosal tunica albuginea does not require surgical
intervention. Nonsteroidal analgesics and ice-packs are
recommended.
In penile fracture, early surgical intervention with closure
of the tunica albuginea is recommended.
Intra-operative flexible cystoscopy is useful to diagnose
urethral injury and to further localise tunical damage
Conservative management of penile fracture is not recom-
mended.
Penetrating penile trauma
Rarely seen in isolation.
Due to gunshot/knife injury, animal or human bites, assault
and industrial or self-inflicted mutilation.
Non-operative management is recommended in small
superficial injuries with intact Bucks fascia.
More significant injuries require surgical exploration and
debridement of necrotic tissue.
In extended injuries of the penis, primary alignment of
the disrupted tissues may allow for acceptable healing
because of the robust penile blood supply.
In avulsion of the penis, resuscitate the patient and
attempt re-implantation of the penis (if not too badly
damaged) - ideally microsurgical.
Blunt Scrotal trauma
May result in testicular dislocation, haematocoele, testicu-
lar rupture and/or scrotal haematoma.
241 Urological Trauma
Dislocation of the testicle is rare. Treat by manual replace-
ment and secondary orchidopexy. If manual reposition
cannot be performed, immediate orchidopexy is indicated.
If haematocele is smaller than three times the size of the
contralateral testis - conservative management.
If large haematocele - explore.
If testicular rupture suspected, explore, evacuate clot and
any necrotic testicular tubules and close the tunica albug-
inea.
Penetrating scrotal trauma
Surgical exploration with conservative debridement of
non-viable tissue.
Primary reconstruction of testis and scrotum can be per-
formed in most cases.
In complete disruption of the spermatic cord, realignment
without vaso-vasostomy may be considered.
In extensive destruction of the tunica albuginea, mobilisa-
tion of a free tunica vaginalis flap can be performed for
testicular closure.
If reconstruction cannot be achieved, orchiectomy is indi-
cated.
In IED blast injury, the extensive loss of genital tissue often
requires complex and staged reconstructive surgical pro-
cedures.
Genital Trauma in Females
In blunt trauma to the external genitalia, imaging studies of
the pelvis with US, CT, or MRI should be performed.
Vulvar haematomas usually do not require surgical inter-
vention, but in massive vulvar haematoma or haemody-
namically unstable patients, surgical intervention, lavage
and drainage is indicated.
In vulvar laceration, suturing after conservative debride-
ment is indicated with concomitant primary repair of any
242 Urological Trauma
associated vaginal injuries.
Mass casualty events, triage and damage control
Definition
A mass casualty event is one in which the number of injured
people is significantly higher than the number of healthcare
providers available.
Causes of mass casualty events
Potential mass casualty events include:
The collapse of buildings or bridges;
earthquakes;
floods;
tsunamis;
train collisions;
aircraft catastrophes;
civilian terrorism.
Triage divides patients into four groups:
1. Patients with life-threatening injuries that require imme-
diate intervention, presenting with Airway compromise,
Breathing failure and/or Circulatory compromise from
ongoing external haemorrhage.
2. Patients with severe but non-life-threatening injuries, in
whom treatment can be acceptably delayed: major frac-
tures, vascular injuries of the limbs and large soft tissue
wounds.
3. Walking wounded with minimal injuries.
4. Patients who are so severely injured that treatment would
require allocation of resources and time that would deny
other, more salvageable patients, timely care. These
patients are given minimal or no treatment, and reevaluat-
ed when resources become available. There is no absolute
definition for this group because triage is individualised
according to the number and severity of casualties related
243 Urological Trauma
to the available resources.
Principles urological consultations during a mass casualty
scenario:
Rule out under-triage by the surgeon in charge, and per-
form a rapid primary survey of every patient.
Avoid unnecessary imaging procedures such as CT scans
and retrograde urethrography. These procedures are
performed later, after mass casualty protocols have been
suspended.
Treat unstable patients who are to have surgery using
damage control principles.
Stable patients with suspected renal injuries should be
transferred to the surgical ward without imaging proce-
dures. Re-evaluate if there is any change in their haemo-
dynamic status, or when possible as dictated by the
constraints of the mass casualty event. Patients managed
in this delayed fashion should be treated according to tra-
ditional trauma management protocols.
Minimal acceptable procedures should be performed
in order to transfer patients to the surgical wards, e.g.
suprapubic drainage of the bladder when bladder or ure-
thral injuries are suspected, clamping and ligation of bleed-
ing vessels from wounds to the external genitalia, etc.
This short booklet text is based on the more comprehensive EAU
guidelines (ISBN 978-90-79754-71-7) available to all members of the
European Association of Urology at their website,
http://www.uroweb.org.
244 Urological Pain Management & Palliative Care
GUIDELINES ON UROLOGICAL PAIN
MANAGEMENT & PALLIATIVE CARE
(Text update March 2013)
A. Paez Borda (chair), F. Charnay-Sonnek, V. Fonteyne,
E. Papaioannou
Hierarchy of general principles of cancer pain manage-
ment
1. Individualised treatment for each patient.
2. Causal therapy to be preferred over symptomatic therapy.
3. Local therapy to be preferred over systemic therapy.
4. Systemic therapy with increasing invasiveness: World
Health Organization (WHO) ladder.
5. Compliance with palliative guidelines.
6. Both psychological counselling and physical therapy from
the very beginning.
The World Health Organizations analgesic ladder
Step 1: non-opioid analgesic Patients with mild to moder-
ate cancer-related pain should be treated with a non-opio-
id analgesic.
Step 2: non-opioid analgesic + weak opioid Patients
who present with moderate to severe pain or who fail to
achieve adequate relief after a trial of a non-opioid analge-
sia should be treated with a weak opioid (e.g. codeine or
tramadol), typically by using a combination product con-
taining a non-opioid (e.g. aspirin or paracetamol) and an
opioid (e.g. codeine, tramadol or propoxyphene).
Step 3: non-opioid analgesic + strong opioid Patients who
present with severe pain or who fail to achieve adequate
relief with step 2 drugs, should receive a strong opioid (e.g.
morphine, fentanyl, oxycodone, methadon, buprenorphine,
245 Urological Pain Management & Palliative Care
or hydromorphone).
Treatment of neuropathic pain
Drug Dosage Frequency
(maximum)
Amitriptyline
(nortiptyline)
25-75 mg Once per day
Gabapentin 600-1200 mg Three times daily
Pregabalin 75-300 mg Twice daily
Tramadol 50-100 mg Four times daily
Recommendations LE GR
Offer amitriptyline and nortriptyline as a first
line treatment for neuropathic pain, with
nortriptyline having fewer side effects.
1b A
TCAs must be used cautiously in patients with
a history of cardiovascular disorders, glaucoma,
and urine retention.
1b A
Duloxetine is the first-line treatment for neuro-
pathic pain due to diabetic polyneuropathy.
2a A
Duloxetine may be tried as an analgesic in other
neuropathic pain syndromes.
3 C
GR = grade of recommendation.
246 Urological Pain Management & Palliative Care
Pain management in urological cancers
Efficacy of the therapeutic options in pain relief (expert
opinion)
Origin of pain/
therapeutic
options
RCC TCC PCa Penile
cancer
Adrenergic
cancer
Testicular
cancer
Bone metastases
Surgery +++ ? + ? ? +
Radiation ++ ++ +++ ! ! !
Radionuclide + ? +++ ? ++ -
Chemotherapy - ? + ? -
Immunotherapy - - - ? ? ?
Hormone therapy - - ++ - - -
Analgesics +++ +++ +++ +++ +++ +++
Soft tissue infiltration
Surgery +++ +++ - ? ? +
Radiation ++ ! ++ ! ! !
Chemotherapy + ++ + ? ++ +++
Immunotherapy + - - ? ? ?
Hormone therapy - - ++ - - -
Analgesics +++ +++ +++ +++ +++ +++
Nerve compression/nerve infiltration
Surgery +++ +++ ++ ? ? ++
Radiation + ! ++ ! ! !
Chemotherapy + ++ + ? ? +++
Immunotherapy + - - ? ? ?
Hormone therapy - - ++ - - -
Analgesics +++ +++ +++ +++ +++ +++
RCC = renal cell carcinoma; TCC = transitional cell carcinoma;
PCa = prostate cancer;
? = no conclusive data on pain control; - = no pain control; + =
low pain control;
++ = moderate pain control; +++ = good pain control.
! Although studies are lacking, patients presenting with bone
247 Urological Pain Management & Palliative Care
metastases or soft tissue metastases should not be refused
for radiotherapy as an antalgic effect can be expected.
ANTICANCER TREATMENT
Recommendation LE GR
Hormonal therapy (orchiectomy, LHRH
analogues, diethylstilboestrol equivalent)
1a A
Total androgen blockade: flare prevention,
second-line
2b B
Intermittent androgen suppression
experimental
3 B
Monotherapy with anti-androgen is an option 2 B
First-line treatment controls disease for 12-18
months, second-line individualised
1b A
Supportive care
Low-dose glucocorticoids 1b A
Chemotherapy
Mitoxantrone plus prednisolone 1b B
Estramustine + vinblastine or etoposide or
paclitaxel
2b B
Docetaxel 1b A
PAIN MANAGEMENT
Recommendation LE GR
Pain assessment (localisation, type, severity,
overall distress)
B
Pain due to painful or unstable bony metastases (single
lesions)
External beam irradiation 1b A
Pain due to painful bony metastases (widespread)
Radioisotopes (89Sr or 153Sm-EDTMP) 2 B
248 Urological Pain Management & Palliative Care
Pain due to painful metastases (many spots)
Bisphosphonates 1b A
Denosumab 1b A
Systemic pain management
WHO analgesic ladder step 1: NSAID or para-
cetamol
1a A
Opioid administration
Dose titration 2 B
Access to breakthrough analgesia 1b A
Tricyclic antidepressant and/or anticonvulsant
in case of neuropathic pain
1a A
Criteria for selecting patients for primary therapy for spinal
cord compression
Absolute criteria Surgery Radiotherapy
Operability Medically
operable
Medically
inoperable
Duration of paraplegia < 48 hours 48 hours
Life expectancy > 3 months < 3 months
Radiosensitivity Highly sensitive
Relative criteria
Diagnosis of primary
tumour
Unknown Known
Bone fragments with
compression
Present Absent
Number of foci of
compression
1 focus > 1 foci
249 Urological Pain Management & Palliative Care
Pain management in transitional cell carcinoma
patients
Recommendations LE GR
In locally advanced bladder cancer, palliative
cystectomy or exenteration might be an option
for symptom relief
3 B
Use radiotherapy to reduce pain and symptoms
of locally advanced bladder cancer
1a B
Use radiotherapy to reduce pain due to bone
metastases
1b A
Specific pain treatment after different urological
operations
Recommendations LE GR
Analgesics should be given on demand during
and after ESWL because not all patients need
pain relief.
3 B
Premedication with NSAIDs or midazolam often
decreases the need for opioids during the pro-
cedure.
2b B
Intravenous opioids and sedation can be used
in combination during ESWL; dosage is limited
by respiratory depression.
3 C
Post-ESWL, analgesics with a spasmolytic effect
are preferable.
3 C
NSAID = nonsteroidal anti-inflammatory drug.
250 Urological Pain Management & Palliative Care
Transurethral procedures
Recommendations LE GR
Post-operative analgesics with a spasmolytic
effect or mild opioids are preferable.
3 C
Antimuscarinic drugs could be helpful in reduc-
ing discomfort resulting from the indwelling
catheter.
3 B
Antimuscarinic drugs may reduce the need for
opioids.
3 B
Laparoscopic procedures
Recommendations LE GR
Low intra-abdominal pressure and good desuf-
flation at the end of the procedure reduces
postoperative pain.
1b A
NSAIDs are often sufficient for postoperative
pain control.
2a B
NSAIDs decrease the need for opioids. 1b B
NSAID = non-steroidal anti-inflammatory drug.
Open surgery
Recommendations LE GR
For postoperative pain control, multimodal
analgesia with a combination of NSAIDs or
paracetamol plus local anaesthetics should be
used.
3 B
If possible, avoid opioids for outpatients. 3 C
251 Urological Pain Management & Palliative Care
Transvaginal surgery
Recommendations LE GR
NSAIDs are often sufficiently effective after
minor or moderate surgery.
2a B
NSAIDs decrease the need for opioids. 1b B
Transperitoneal laparotomy
Recommendations LE GR
The most effective method for systemic admin-
istration of opioids is PCA, which improves
patient satisfaction and decreases the risk of
respiratory complications.
1b A
Epidural analgesia, especially PCEA, provides
superior postoperative analgesia, reducing
complications and improving patient satisfac-
tion, and is preferable to systemic techniques.
1b A
PCA = patient-controlled analgesia; PCEA patient-controlled
epidural analgesia
Retroperitoneal approach - flank incision - thoracoab-
dominal approach
Recommendations LE GR
Epidural analgesia, especially PCEA, provides
superior postoperative analgesia, reducing
complications and improving patient satisfac-
tion and is therefore preferable to systemic
techniques (see Sections 5.3.5.2 and 5.3.5.3).
1b A
PCEA patient-controlled epidural analgesia
252 Urological Pain Management & Palliative Care
Dosage and method of delivery of some important
analgesics
Dosage and delivery of NSAIDs
Drug Daily dose Route of
administration
Conventional NSAIDs (non-selective COX inhibitors)
Ketorolac 10-30 mg four
times daily
Orally or iv
Ibuprofen 400 mg three
times daily
Orally
Ketoprofen 50 mg four times
daily
Orally or iv
Diclofenac 75 mg twice daily Orally or iv
50 mg three times
daily
Orally or iv
100 mg twice daily Rectally
COX-2 selective inhibitors
Meloxicam 15 mg once per day Orally
Lornoxicam 4-8 mg twice daily Orally or iv
Celecoxib 200 mg once per
day
Orally
Parecoxib 40 mg once or
twice daily
iv form only
Etoricoxib 90-120 mg once
daily
Orally
253 Urological Pain Management & Palliative Care
Dosage and delivery of paracetamol, metamizole and its
combinations with opioids
Drug Method of
administration
Single dose
(mg)
Maximal dose
(mg/day)
Paracetamol Orally 500-1000 4000 (50 mg/
kg)
Paracetamol iv 1000 4000 (50 mg/
kg)
Metamizole Orally 500-1000 4000
Metamizole iv 1000-2500 5000
Paracetamol Opioid Times per
day
Route of
administration
Paracetamol
1 g
Codeine 60 mg Four Orally or
rectally
Paracetamol
600-650 mg
Codeine 60 mg Four Orally or
rectally
Paracetamol
500 mg
Codeine 30 mg Four Orally or
rectally
Paracetamol
300 mg
Codeine 30 mg Four Orally or
rectally
Paracetamol
650 mg
Dextropropoxy-
phene 65 mg
Four Orally
Paracetamol
600-650 mg
Tramadol
75-100 mg
Four Orally
Paracetamol
325 mg
Oxycodone
5 mg
Four Orally
254 Urological Pain Management & Palliative Care
Dose and delivery of opioids
Drug Method of
administra-
tion
Common
single dose
(mg)
Maximal
dose (mg)
Tramadol Orally 50 400-600
Tramadol iv 50-100 400-600
Dihydrocodeine Orally 60-120 240
Piritramid sc/im 15-30 120
Pethidine Orally 25-150 500
Pethidine Rectally 100 500
Pethidine sc/im 25-150 500
Pethidine iv 25-100 500
Morphine* Orally Starting
with 10
No maximal
dose
Morphine* Rectally Starting
with 10
No maximal
dose
Morphine* sc/im Starting
with 5
No maximal
dose
Morphine* iv Starting
with 2
No maximal
dose
Morphine* Iv (PCA) 0.5-2.5 mg
bolus
10-15 min
lockout
No maximal
dose
*Strong opioids have no real upper dose limit (except
buprenorphine). The dose must be titrated in correlation
with pain relief and depending on the individual strength of
unwanted effects such as respiratory depression.
*A simple way of calculating the daily dose of morphine for
adults (20-75 years) is: 100 - patients age = morphine per day
in mg.
255 Urological Pain Management & Palliative Care
Common equi-analgesic doses for parenteral and oral
administration of opioids*
Drug Parenteral (mg) Oral (mg)
Morphine 10 30
Fentanyl 0.1 -
Pethidine 75 300
Oxycodone 15 20-30
Dextropropoxyphene - 50
Tramadol 37.5 150
Codeine 130 200
*All listed opioid doses are equivalent to parenteral morphine
10 mg. The intrathecal opioid dose is 1/100, and the epidural
dose 1/10 of the dose required systemically.
Recommendations LE GR
Transdermal fentanyl is equally effective to
morphine. The incidence of side effects is lower
than for morphine.
1b A
Oral transmucosal administration of fentanyl
should be used to provide rapid relief of break-
through pain. The starting dose is 400 g, or 200
g in the elderly and those with a history of opi-
oid sensitivity or underlying pulmonary disease.
2a B
Recommendations LE GR
Dexamethasone 1-2 mg twice daily can be a
valuable adjuvant in the treatment of pain in
advanced cancer.
2a B
If possible, avoid opioids for outpatients. 3 C
256 Urological Pain Management & Palliative Care
Typical PCA dosing schedule
Drug
(concentration)
Bolus size Lockout
interval (min)
Continuous
infusion
Morphine
(1 mg/mL)
0.5-2.5 mg 5-10 0.01-0.03 mg/
kg/h
Fentanyl
(0.01 mg/mL)
10-20 g 5-10 0.5-0.1 g/
kg/h
Pethidine
(10 mg/mL)
5-25 mg 5-10 -
PCA = patient controlled analgesia
Recommendations LE GR
The use of intravenous patient controlled
analgesia is recommended because it provides
superior postoperative analgesia, improving
patient satisfaction and decreasing risk of respi-
ratory complications.
1b A
Typical PCEA dosing schemes
Drug Demand
dose
Lockout
interval (min)
Continuous
rate
Morphine 100-200 g 10-15 300-600 g/h
Fentanyl 10-15 g 6 80-120 g/h
Pethidine 30 mg 30 -
Bupivacaine
0.125% +
fentanyl 4 g/mL
2 mL 10 4 mL/h
Ropivacaine
0.2% + fentanyl
5 g/mL
2 mL 20 5 mL/h
257 Urological Pain Management & Palliative Care
Typical epidural dosing schemes*
Drug Single dose Continuous
infusion
Morphine 1-5 mg 0.1-1 mg/h
Fentanyl 50-100 g 25-100 g/h
Sufentanil 10-50 g 10-20 g/h
Pethidine 10-30 mg 10-60 mg/h
Bupivacaine 0.125% or
ropivacaine 0.2% + fentanyl
2 g/mL
10-15 mL 2-6 mL/h
*l-bupivacaine doses are equivalent to those of bupivacaine.
Recommendations LE GR
Epidural analgesia, especially PCEA, provides
superior post-operative analgesia, reducing
complications and improving patient satisfac-
tion, and is therefore preferable to systemic
techniques.
1b A
If possible, avoid opioids for outpatients. 3 C
258 Urological Pain Management & Palliative Care
Peri- and post-operative pain management
Recommendations LE GR
The use of paracetamol is recommended for
postoperative pain management because it
reduces consumption of opioids.
1b B
Administer paracetamol as a single therapy to
alleviate mild postoperative pain without major
adverse effects.
2a B
Avoid long-term use of COX inhibitors in
patients with atherosclerotic cardiovascular
disease.
2a B
Acute postoperative pain
Exclude medical/surgical emergency
Exclude medical/surgical emergency
No pain Mild (VAS score 1-3)
(ESWL, transurethral,
percutaneous endoscopic,
transvaginal procedures)
Moderate (VAS score 4-6)
(Laparoscopic, minor operations
of the scrotum/penis and the
inguinal approach)
Severe (VAS score 7-10)
(Open surgery - perineal,
transperitoneal, suprapubic,
retropubic extraperitoneal
laparotomy, retroperitoneal
approach, flank incision,
thoracoabdominal approach)
Pain level reassessment
and evaluation every
4-6 hrs unless patient
expresses discomfort
Paracetamol 500mg-1g x 4 iv
and/or NSAIDs (diclofenac
50mg x3 iv, ketorolac 10-30 mg
x 4 iv, lornoxicam 4-8mg x 2 iv,
parecoxib 40mg x 2 iv) and/or
metamizole 500-1000mg x 4 iv
or paracetamol 500-1000mg
plus codeine 30-60mg x 4
orally.
In case of persistent pain
pethidine 50-100mg iv or
tramadol 50-100 mg iv prn.
Paracetamol 500mg-1g x 4 iv
and/or NSAIDs (diclofenac
50mg x3 iv, ketorolac 10-30 mg
x 4 iv, lornoxicam 4-8mg x 2 iv,
parecoxib 40mg x 2 iv) and/or
metamizole 500-1000mg x 4 iv
or paracetamol 500-1000mg
plus codeine 30-60mg x 4
orally.
Pethidine 50-100mg x 6 iv or
tramadol 50-100 mg x 6 iv or
morphine 5mg starting dose x
4-6 times per day sc/im or 2mg
starting dose x 6 iv.
In case of persistent pain add or
increase morphine dose by 2mg
bolus in 1 hr increments
Paracetamol 500mg-1g x 4 iv
and/or NSAIDs (diclofenac
50mg x3 iv, ketorolac 10-30 mg
x 4 iv, lornoxicam 4-8mg x 2 iv,
parecoxib 40mg x 2 iv) and/or
metamizole 500-1000mg x 4 iv
PCA with morphine iv (0.5-
2.5mg bolus, 10-15 min lockout)
PCEA with morphine 100-
200g demand dose, lockout
interval 10-15 min and
continuous rate 300-600g/h
ropivacaine 0.2% 2ml
demand dose, and continuous
rate 5ml/h or bupivacaine
0.125% 2ml demand dose and
continuous rate 4ml/h.
In case of persistent pain extra
morphine 2-5 mg iv or morphine
1-5mg 10-15ml bupivacaine
0.125% or ropivacaine 0,2% bolus
epidurally in 1 hr increments.
Refer to appropriate level of treatment
259 Urological Pain Management & Palliative Care
The use of intravenous patient controlled
analgesia is recommended because it provides
superior postoperative analgesia, improving
patient satisfaction and decreasing risk of respi-
ratory complications.
1b A
Neural blocks
Local anaesthetic blocks (intermittent and continuous) can
be used after urological surgical operations to
supplement postoperative analgesia.
Examples of neural blocks
Procedure Drug/dosage
Iliohypogastric or ilioinguinal
nerve infiltration after
hernia repair
10-20 mL bupivacaine or
ropivacaine 0.25-0.5%
Intercostal nerve infiltration 5-10 mL bupivacaine or
ropivacaine 0.25-0.5%
Continuous intrapleural
infusion
10 mL/h bupivacaine or
ropivacaine 0.1-0.2%
Perioperative pain management in children
Drug Dosing Route of
administra-
tion
Category
Ketamine 6 mg/kg Oral, intrana-
sal, im
NMDA antag-
onist
Midazolam 0.5 mg/kg Oral, intrana-
sal, rectally
Benzo-
diazepine
Dexmedeto-
midine
4 g/kg Oral, intra-
nasal
2-receptor
agonist
Clonidine 4 g/kg Oral 2-receptor
agonist
260 Urological Pain Management & Palliative Care
Pentobarbital 4-6 mg/kg im Barbiturate
Chloral hydrate 50-100
mg/kg
Oral Barbiturate
Methohexital 25-30 mg/
kg
Rectally Barbiturate
Recommendations LE GR
Apply EMLA locally to alleviate venipuncture
pain in children.
1b A
Dosage of analgesics in children for postoperative
analgesia
Drug Dose Route of
admini-
stration
Severity of
surgical
procedure
Paracetamol 10-15 mg/kg
every 4 h
20-30 mg/kg
every 6 h
Oral, rectally Minor
Minor
Ibuprofen 10-15 mg/kg
every 6 h
Oral, iv, rectally Minor,
medium
Naproxen 6-8 mg/kg
every 8-12 h
Oral, iv, rectally Minor,
medium
Codeine 0.5-1 mg/kg
every 3-4 h
Oral Minor,
medium
Morphine 0.1 mg/kg
every 2-4 h
Infusion: 0.03
mg/kg/h 0.3
mg/kg every
3-4 h
Oral, iv, sc Medium,
major
Oxycodone 0.1-0.2 mg/kg
every 3-4 h
Oral Medium
261 Urological Pain Management & Palliative Care
Hydro-
morphone
0.04-0.08 mg/
kg every 3-4 h
Oral Medium
Tramadol 1 mg/kg every
4-6 h
iv Medium,
major
Pethidine 2-3 mg/kg
every 3-4 h
iv Medium,
major
Non-traumatic acute flank pain
Laboratory evaluation
All patients with acute flank pain require a urine test (red
and white cells, bacteria or urine nitrite), blood cell count,
and serum creatinine measurement. In addition, febrile
patients require C-reactive protein (CRP) and urine culture.
Pyelonephritis obstructive uropathy should be suspected
when the white blood count exceeds 15,000/mm3.
Recommendations LE GR
Febrile patients (> 38C) with acute flank pain
and/or with a solitary kidney need urgent imag-
ing.
4 B
Unenhanced helical computed tomography is
the diagnostic imaging modality with the high-
est sensitivity and specificity for evaluation of
non-traumatic acute flank pain.
A
Ultrasound can be an alternative to unen-
hanced helical computed tomography in the ini-
tial approach to non-traumatic acute flank pain.
A
In patients presenting with acute flank pain
NSAIDs such as diclofenac (75 mg bolus) and
dipyrone (1-2 g slow iv injection) are the drugs of
first choice.
1a A
262 Urological Pain Management & Palliative Care
Diagnostic approach to non-traumatic acute flank pain

CT = computed tomography; UTI = urinary tract infection.
Non-urologic
fank pain
Normal + normal
urinalysis
Normal +
abnormal
urinalysis
(leucocyturia,
haematuria
or bacteriuria)
Abnormal
Further
investigation and
appropriate
treatment
Genitourinary
abnormality
Non-genitourinary
abnormality
Refer patient
Refer patient
Check for :
renal infarct
renal abscess
renal vein
thrombosis
tumour
cyst
haematoma
urinoma
extrarenal mass
No stone
No hydronephrosis
Stone
Ureteral obstruction
Check for:
ureteral tumour
papillary necrosis
upj obstruction
retroperitoneal
fbrosis
Hydronephrosis
Treat
infection
No stone
Management to
relieve pain or
obstruction
No UTI
Stone
Urinary
drainage and
infection
treatment
No UTI UTI
Stone
management
Stone
management
UTI
History, physical examination, temperature, urinalysis pain treatment
Acute Flank Pain
If not conclusive
Ultrasonography and/or unenhanced CT scan
263 Urological Pain Management & Palliative Care
Initial emergency treatment
Systemic analgesia
Pain relief is usually the first, most urgent, therapeutic step:
A a slow intravenous infusion of dipyrone, 1 g or 2 g, is just
as effective as diclofenac (75mg bolus) (LE: 1a).
Intravenous papaverine (120 mg)can effectively and safely
relieve patients not responding to conventional agents
(diclofenac) and can be an alternative to diclofenac in
patients with contraindications to NSAIDS (LE: 1b).
The combination of intravenous morphine + ketorolac
seems superior to either drug alone and appears to be
associated with a decrease in rescue analgesia.
Upper urinary tract decompression
If pain relief cannot be achieved using medical therapy and
there are signs of infection and of impaired renal function,
upper urinary tract drainage should be carried out (Ureteral
stenting or percutaneous nephrostomy).
Indications for stenting for urgent relief of obstruction
Urine infection with urinary tract obstruction
Urosepsis
Intractable pain and/or vomiting
Obstruction of a solitary or transplanted kidney
Bilateral obstructing stones
Ureteral calculus obstruction in pregnancy
Palliative care
Before assuming the professional responsibility of terminal
care, concepts on parenteral hydration and antibiotics usage
should be clarified.
Protocols for communicating with patients about major
topics in palliative care
264 Urological Pain Management & Palliative Care
Curriculum Emanuel LL, von Gunten CF, Ferris FD, eds. The
Education in Palliative and End-of-life Care (EPEC) Curriculum:
The EPEC Project, 1999, 2003.
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265 Urological Pain Management & Palliative Care
Treatment of physical symptoms
Dyspnoea and respiratory symptoms
Recommendations LE GR
Benzodiazepines can be considered when
opioids and non-pharmacological measures fail
to control breathlessness.
1a A
Anorexia
Recommendations
Thalidomide (50 mg/day, orally, for 2 weeks) is effective
against cancer-related anorexia
Vomiting
Recommendations LE GR
Dexamethasone is not effective in metoclopra-
mide-refractory nausea.
1b A
Patients with a high risk of vomiting are effec-
tively treated with a combination of dexam-
ethasone and 5-HT3 and neurokinin 1 receptor
antagonists.
1a A
In patients with moderate risk of vomiting, pal-
onosetron combined with dexamethasone is
recommended.
1a A
Patients receiving radiotherapy and experi-
encing emesis can be effectively treated with
combined 5-HT3 receptor antagonist and dex-
amethasone.
1a A
Terminal care
Palliative sedation is one of the alternatives for terminally ill
patients.
266 Urological Pain Management & Palliative Care
Algorithm for the decision on symptom refractoriness
Source: Royal Dutch Medical Association (KNMG). Guideline
for Palliative Sedation. Utrecht, 2009.
Palliative sedation
Palliative sedation never aims to hastening death.
Subcutaneous administration is the preferred route and mida-
zolam the drug of choice.
Is the symptom
treatable?
Yes
Yes
Yes
No
No
The symptom is refractory
The symptom is not refractory
Can treatment be given
without unacceptable
side effects?
Will the treatment take
effect quickly enough?
267 Urological Pain Management & Palliative Care
Drug Bolus Continuous administration
Midazolam Start with
10mg s.c.If
necessary
every 2 hrs 5
mg s
Initial dose 1.5-2.5 mg/hr s.c./
i.v.If the desired effect is not
achieved, in-crease the dose by
50% after a minimum of 4 hrs,
always in combination with a
bolus of 5 mg s.c. If risk factors
are present (age>60,weight<60
kg, severe kidney or liver func-
tion disorder, very low serum
albumin and/or co-medication
that could exacer-bate the
effect of sedation):
- lower initial dose (0.5-1.5 mg/
hr), and
- longer interval (6-8 hrs) before
increasing maintenance dose.
In the case of doses higher
than 20mg/hr, see phase 2.
Levome-
promazine
25 mg .c./i.v,
possibly 50 mg
after 2 hrs
0.5-8 mg/hr s.c./i.v. in combina-
tion with midazolam. After 3
days, halve the dose to prevent
drug accumulation. If the
desired effect is not achieved,
stop administering midazolam
and levomepromazine; see
phase 3
Propofol 20-50 mg i.v. 20 mg/hr i.v., increase by
10 mg/hr every15 minutes.
Administration under the
supervision of an anaesthesi-
ologist is advisable. In hospital,
this may be considered for
phase 2
Source: Royal Dutch Medical Association (KNMG). Guideline
for Palliative Sedation. Utrecht, 2009.
268 Urological Pain Management & Palliative Care
This short booklet is based on the more comprehensive EAU
guidelines (ISBN 978-90-79754-71-7), available to all members of the
European Association of Urology at their website,
http://www.uroweb.org.
269 Chronic Pelvic Pain
GUIDELINES ON CHRONIC PELVIC PAIN
(Complete text update February 2012)
D. Engeler (chairman), A.P. Baranowski, J. Borovicka,
P. Dinis-Oliveira, S. Elneil, J. Hughes, E.J. Messelink,
A. van Ophoven, Y. Reisman, A.C. de C. Williams
Eur Urol 2004;46(6):681-9
Eur Urol 2010;57(1):35-48
This pocket version aims to synthesise the important clini-
cal messages described in the full text and is presented as a
series of graded action based recommendations, which fol-
low the standard for levels of evidence used by the EAU (see
Introduction chapter full text guidelines).
Figure 1: Predisposing factors, cause, central en peripheral
mechanisms
Causes
surgery
trauma
infection
Peripheral nerve injury
Abnormal peripheral
aferent signalling
Peripheral sensitisation
Increased peripheral
aferent signalling
Central sensitisation
Regional and systemic changes
Referred pain, viscero-visceral hyperalgesia, viscero-somatic hyperalgesia. Trophic, autonomic, endocrine and
immunological responses
Abnormal central
aferent signalling
Consequences include:
sensory problems
Abnormal central
eferent signalling
Consequences include:
changes in organ function
Abnormal central
processing
Psychological, behavioural and
sexual consequences
Predisposing factors
genetics
psychological state
recurrent somatic trauma
270 Chronic Pelvic Pain
Table 1: Classification of chronic pelvic pain syndromes
Axis I
Region
Axis II
System
Axis III
End-organ as pain syndrome as identified
from Hx, Ex and Ix
Axis IV
Referral
character-
istics
Axis V
Temporal
characteristics
Axis VI
Character
Axis VII
Associated
symptoms
Axis VIII
Psychological
symptoms
Chronic
pelvic
pain
Specific
disease
associated
pelvic pain
OR
Pelvic pain
syndrome
Urological Prostate Suprapubic
Inguinal
Urethral
Penile/clitoral
Perineal
Rectal
Back
Buttocks
Thighs
ONSET
Acute
Chronic
ONGOING
Sporadic
Cyclical
Continuous
TIME
Filling Emptying
Immediate post
Late post
TRIGGER
Provoked
Spontaneous
Aching
Burning
Stabbing
Electric
UROLOGICAL
Frequency
Nocturia
Hesitance
Dysfunctional flow
Urge
Incontinence
GYNAECOLOGICAL
Menstrual
Menopause
GASTROINTESTINAL
Constipation
Diarrhoea
Bloatedness
Urge
Incontinence
NEUROLOGICAL
Dysaesthesia
Hyperaesthesia
Allodynia
Hyperalegesie
SEXUOLOGICAL
Satisfaction
Female dyspareunia
Sexual avoidance
Erectile dysfunction
Medication
MUSCLE
Function impairment
Fasciculation
CUTANEOUS
Trophic changes
Sensory changes
ANXIETY
About pain
or putative
cause of pain
Catastrophic
thinking about
pain
DEPRESSION
Attributed to
pain or impact
of pain
Attributed to
other causes
Unattributed
PTSD
SYMPTOMS
Re-experiencing
Avoidance
Bladder
Scrotal
Testicular
Epididymal
Penile Urethral
Postvasectomy
Gynaecological Vulvar
Vestibular
Clitoral
Endometriosis associated
CPPS with cyclical exacerbations
Dysmenorrhoea
Gastrointestinal Irritable bowel
Chronic anal
Intermittent chronic anal
Peripheral
nerves
Pudendal pain syndrome
Sexological Dyspareunia
Pelvic pain with sexual dysfunction
Psychological Any pelvic organ
Musculo-skeletal Pelvic floor muscle
Abdominal muscle
Spinal
Coccyx
271 Chronic Pelvic Pain
Table 1: Classification of chronic pelvic pain syndromes
Axis I
Region
Axis II
System
Axis III
End-organ as pain syndrome as identified
from Hx, Ex and Ix
Axis IV
Referral
character-
istics
Axis V
Temporal
characteristics
Axis VI
Character
Axis VII
Associated
symptoms
Axis VIII
Psychological
symptoms
Chronic
pelvic
pain
Specific
disease
associated
pelvic pain
OR
Pelvic pain
syndrome
Urological Prostate Suprapubic
Inguinal
Urethral
Penile/clitoral
Perineal
Rectal
Back
Buttocks
Thighs
ONSET
Acute
Chronic
ONGOING
Sporadic
Cyclical
Continuous
TIME
Filling Emptying
Immediate post
Late post
TRIGGER
Provoked
Spontaneous
Aching
Burning
Stabbing
Electric
UROLOGICAL
Frequency
Nocturia
Hesitance
Dysfunctional flow
Urge
Incontinence
GYNAECOLOGICAL
Menstrual
Menopause
GASTROINTESTINAL
Constipation
Diarrhoea
Bloatedness
Urge
Incontinence
NEUROLOGICAL
Dysaesthesia
Hyperaesthesia
Allodynia
Hyperalegesie
SEXUOLOGICAL
Satisfaction
Female dyspareunia
Sexual avoidance
Erectile dysfunction
Medication
MUSCLE
Function impairment
Fasciculation
CUTANEOUS
Trophic changes
Sensory changes
ANXIETY
About pain
or putative
cause of pain
Catastrophic
thinking about
pain
DEPRESSION
Attributed to
pain or impact
of pain
Attributed to
other causes
Unattributed
PTSD
SYMPTOMS
Re-experiencing
Avoidance
Bladder
Scrotal
Testicular
Epididymal
Penile Urethral
Postvasectomy
Gynaecological Vulvar
Vestibular
Clitoral
Endometriosis associated
CPPS with cyclical exacerbations
Dysmenorrhoea
Gastrointestinal Irritable bowel
Chronic anal
Intermittent chronic anal
Peripheral
nerves
Pudendal pain syndrome
Sexological Dyspareunia
Pelvic pain with sexual dysfunction
Psychological Any pelvic organ
Musculo-skeletal Pelvic floor muscle
Abdominal muscle
Spinal
Coccyx
272 Chronic Pelvic Pain
Figure 2: an algorithm for diagnosing and managing CPP
Figure 3: an algorithm for pain management
Chronic Pelvic Pain

see
chapter 3
see
chapter 4
see
chapter 5
see
chapter 7
Organ specic symptoms
present
urology gynaecology
gastro-
enterology
sexology
Treat according to
specic disease
guidelines
Symptom of a well
known disease
Go to:
Pain management
(Fig. 3)
Specic disease associated
pelvic pain
Pelvic pain syndrome
see
chapter 9
pelvic oor
no
yes
neurology
see
chapter 6
no
yes
History
Physical
examination
Holistic approach
Psychology Physiotherapy Pain medicine
see chapter 8 see chapter 9 see chapter 10
Multidisciplinary team
273 Chronic Pelvic Pain
Figure 4: phenotyping and assessment algorithm for CPP
UROLOGICAL ASPECTS OF CHRONIC PELVIC PAIN
PROSTATE PAIN SYNDROME
Recommendations: assessment and diagnosis pros-
tate pain syndrome (PPS)
GR
Specific diseases with similar symptoms must be
excluded. It is therefore recommended to adapt diag-
nostic procedures to the patient and to aim at identi-
fying them.
A
After primary exclusion of specific diseases, patients
with symptoms according to the above definition
should be diagnosed with PPS.
A
A validated symptom and quality of life scoring instru-
ment, such as the NIH-CPSI, should be considered for
initial assessment as well as for follow-up.
B
Urology
Psychology
Organ
specic
Infection
Tender
muscle
Phenotyping
Urinary ow, micturition diary, cystoscopy, ultrasound, uroowmetry
Neurological
Assessment
History of negative experiences, important loss, coping mechanism,
depression
Ask for gynaecological, gastro-intestinal, ano-rectal, sexological complaints
Gynaecological examination, rectal examination
Semen culture and urine culture, vaginal swab, stool culture
Ask for neurological complaints (sensory loss, dysaesthesia).
Neurological testing during physical examination: sensory problems,
sacral reexes and muscular function
Palpation of the pelvic oor muscles, the abdominal muscles and the
gluteal muscles
274 Chronic Pelvic Pain
It is recommended to assess PPS associated negative
cognitive, behavioural, sexual, or emotional conse-
quences, as well as symptoms of lower urinary tract
and sexual dysfunctions.
B
Recommendations: treatment of prostate pain syn-
drome (PPS)
GR
Consider multimodal and phenotypically directed
treatment options for PPS.
B
Alpha-blockers are recommended for patients with a
duration of PPS < 1 year.
A
Single use of antimicrobial therapy (quinolones or
tetracyclines) is recommended in treatment-nave
patients over a minimum of 6 weeks with a duration of
PPS < 1 year.
A
NSAIDs are recommended for use in PPS, but long-
term side effects have to be considered.
B
Allopurinol is not recommended for use in PPS. B
Phytotherapy might be used in patients with PPS. B
Consider high-dose pentosan polysulphate to improve
symptoms and quality of life in PPS.
A
Pregabalin is not recommended for use in PPS. A
Perineal extracorporeal shock wave therapy might be
considered for the treatment of PPS.
B
Electroacupuncture might be considered for the treat-
ment of PPS.
B
Posterior tibial nerve stimulation might be considered
for the treatment of PPS.
B
TUNA of the prostate is not recommended for the
treatment of PPS.
B
For PPS with significant psychological distress, psy-
chological treatment focussed on PPS should be
attempted.
B
TUNA = transurethral needle ablation
275 Chronic Pelvic Pain
Figure 5: assessment and treatment algorithm for PPS
BLADDER PAIN SYNDROME
Table 2: ESSIC classification of types of BPS according to the results
of cystoscopy with hydrodistension and biopsies
Cystoscopy with hydrodistension
Not
done
Normal Glomerulations
a
Hunners
lesion
b
Biopsy
Not done XX 1X 2X 3X
Normal XA 1A 2A 3A
Inconclusive XB 1B 2B 3B
Positive
c
XC 1C 2C 3C
a
Cystoscopy: glomerulations grade 23
b
Lesion per Falls definition with/without glomerulations
c
Histology showing inflammatory infiltrates and/or detrusor
mastocytosis and/or granulation tissue and/or intrafascicular
fibrosis
Urine culture
Uroowmetry
Transrectal
US prostate
NIH-CPSI
scoring list
Pelvic oor
muscle testing
Assessment
Grade A
recommended
Phenotyping
Treatment
Grade B
recommended
Not recommended
Alpha-blockers when duration is < 1 year
Single use antibiotics (6 weeks) when duration
is < 1 year
NSAIDs. Be aware of long-term side eects
Phytotherapy
High dose Pentosan polysulfate to improve QoL
and symptoms
Allopurinol [B]

Pregabalin [A]
Perineal extracorporeal shock wave therapy
Electroacupuncture
Percutaneous tibial nerve stimulation (PTNS)
TransUrethral Needle Ablation (TUNA) [B]
Psychological treatment focused on the pain
276 Chronic Pelvic Pain
Recommendations: assessment and diagnosis blad-
der pain syndrome (BPS)
GR
Specific diseases with similar symptoms have to be
excluded. It is therefore recommended to adapt diag-
nostic procedures to each patient and aim at identify-
ing them.
A
After primary exclusion of specific diseases, patients
with symptoms according to the above definition
should be diagnosed with BPS by subtype and phe-
notype.
A
A validated symptom and quality of life scoring instru-
ment should be considered for initial assessment as
well as for follow-up.
B
BPS associated non-bladder diseases should be
assessed systematically.
A
BPS associated negative cognitive, behavioural, sexu-
al, or emotional consequences should be assessed.
A
Recommendations: treatment bladder pain
syndrome (BPS)
GR
Offer subtype and phenotype-oriented therapy for
the treatment of BPS.
A
Multimodal behavioural, physical and psychological
techniques should always be considered alongside
oral or invasive treatments for BPS.
A
Opioids might be used in BPS in disease flare-ups.
Long-term application solely if all treatments failed.
C
Corticosteroids are not recommended as long-term
treatment.
C
Offer hydroxyzine for the treatment of BPS. A
277 Chronic Pelvic Pain
Consider cimetidine as valid oral option before inva-
sive treatments.
B
Administer amitriptyline for use in BPS. A
Offer oral pentosanpolysulphate sodium for the treat-
ment of BPS.
A
Treatment with oral pentosanpolysulphate sodium
plus subcutaneous heparin is recommended especially
in low responders to pentosanpolysulphate sodium
alone.
A
Antibiotics can be offered when infection is present
or highly suspected.
C
Prostaglandins are not recommended. Insufficient
data on BPS, adverse effects considerable.
C
Cyclosporin A might be used in BPS but adverse effects
are significant and should be carefully considered.
B
Duloxetin is not recommended for BPS treatment. C
Oxybutynin might be considered for the treatment
of BPS.
C
Gabapentin might be considered in oral treatment
of BPS.
C
Administer intravesical lidocain plus sodium bicarbo-
nate prior to more invasive methods.
A
Administer intravesical pentosanpolysulphate sodium
before more invasive treatment alone or combined with
oral pentosanpolysulphate sodium.
A
Consider intravesical heparin before more invasive
measures alone or in combination treatment.
C
Consider intravesical hyaluronic acid before more
invasive measures.
B
278 Chronic Pelvic Pain
Consider intravesical chondroitin sulphate before
more invasive measures.
B
Administer intravesical DMSO before more invasive
measures.
A
Consider intravesical bladder wall and trigonal injection of
BTX-A if intravesical instillation therapies failed.
C
Administer submucosal injection of BTX-A plus
hydrodistension if intravesical instillation therapies
failed.
A
Intravesical therapy with Bacillus Calmette Gurin is
not recommended in BPS.
A
Intravesical therapy with clorpactin is not recom-
mended in BPS.
A
Intravesical therapy with vanilloids is not recom-
mended in BPS.
C
Bladder distension is not recommended as a treat-
ment of BPS.
C
Electromotive drug administration might be consid-
ered before more invasive measures.
C
Consider transurethral resection (or coagulation or
laser) of bladder lesions, but in BPS type 3 C only.
B
Neuromodulation might be considered before more
invasive interventions.
B
Consider bladder training in patients with little pain. B
Consider manual and physical therapy in first
approach.
B
Consider diet avoidance of triggering substances. C
Accupuncture is not recommended. C
279 Chronic Pelvic Pain
Consider psychological therapy in multimodal
approach.
B
All ablative organ surgery should be last resort for
experienced and BPS knowledgeable surgeons only.
A
DMSO = dimethyl sulphoxide.
Figure 6: diagnosis and therapy of BPS
Urine culture
Uroowmetry
Cystoscopy with
hydrodistension
Bladder biopsy
Pelvic oor
muscle testing
Assessment
Grade A
recommended
Micturition diary
Treatment
Grade B
recommended
Not recommended
Standard: Hydroxyzine, Amitriptyline,
Pentosanpolysulphate
Intravesical: PPS, DMSO, onabotulinum toxin A
plus hydrodistension
Oral: Cimetidine, cyclosporin A
Intravesical: hyaluronic acid, chondroitin sulphate
Bacillus Calmete Gurin
Intravesical Chlorpactin
Electromotive drug administration for intravesical
drugs
Neuromodulation, bladder training, physical
therapy
Psychological therapy
Data on surgical treatment are largely variable
Phenotyping
ICSI score list
Other comments
Coagulation and laser only for Hunners lesions
280 Chronic Pelvic Pain
Figure 7: algorithm for BPS Type 3 C
SCROTAL PAIN SYNDROME
Recommendations: treatment of scrotal pain syn-
drome
GR
Start with general treatment options for chronic pel-
vic pain (see chapter 10).
A
Inform about the risk of postvasectomy pain when
counselling patients planned for vasectomy.
A
To reduce the risk of scrotal pain, open instead of
laparoscopic inguinal hernia repair is recommended.
A
TUR / laser
yes
Adequate:
* Retreat when
necessary
Inadequate:
* Start other
treatment
* Oral agents
* TENS
* Complementary
medicine
Inadequate relief:
* start Intravesical
therapy
Still inadequate response:
* Refer to specialist
pain management unit
Bladder Pain Syndrome
no
Hunner lesion at cystoscopy
281 Chronic Pelvic Pain
It is recommended that during inguinal hernia repair
all the nerves in the spermatic cord are identified.
A
For patients who are treated surgically, microsurgical
denervation of the spermatic cord is recommended.
A
For patients who do not benefit from denervation it is
recommended to perform epididymectomy.
B
We recommend that orchiectomy should not be
done, unless all other therapies, including pain man-
agement assessment have failed.
C
Figure 8: assessment and treatment algorithm for scrotal
pain syndrome
Semen culture
Uroowmetry
Ultrasound
scrotum
(see full text)
Pelvic oor
muscle testing
Assessment
Grade A
recommended
Phenotyping
Treatment
Grade B
recommended
Grade C
recommended
Other
comments
General treatment options for chronic pelvic
pain - chapter 10
Inform patients undergoing vasectomy about the
risk of pain
Microsurgical denervation of the spermatic cord
Epididymectomy, in case patient did not benet
from denervation
In case all other therapies, including pain
management assessment have failed,
orchiectomy is an option.
Ultrasound has no clinical implications on the
further treatment although physicians tend to
still use ultrasound to reassure the patient
For surgeons: open hernia repair yields less
scrotal pain
For surgeons: identify all nerves during hernia
repair
282 Chronic Pelvic Pain
URETHRAL PAIN SYNDROME
Recommendations: treatment of urethral pain syn-
drome
GR
Start with general treatment options for chronic pel-
vic pain (see chapter 10).
A
It is recommended that patients with urethral pain
syndrome are treated in a multidisciplinary and multi-
modal programme.
B
When patients are distressed, it is recommended to
refer them for pain-relevant psychological treatment
to improve function and quality of life.
B
Figure 9: assessment and treatment algorithm for urethral
pain syndrome
Uroowmetry
Micturition
diary
Pelvic oor
muscle testing
Phenotyping
Assessment
Grade A
recommended
Treatment
Grade B
recommended
Other comments
General treatment options for chronic pelvic
pain - chapter 10
Treat in a multidisciplinary and multimodal
programme
Pain-relevant psychological treatment to improve
QoL and function
Data on urethral pain are very sparse and of
limited quality
283 Chronic Pelvic Pain
GYNAECOLOGICAL ASPECTS OF CHRONIC PELVIC
PAIN
Recommendations: gynaecological aspects in chron-
ic pelvic pain
GR
All women with pelvic pain should have a full gynae-
cological history and evaluation, and including lapar-
oscopy is recommended to rule out a treatable cause
(e.g. endometriosis).
A
Provide therapeutic options such as hormonal thera-
py or surgery in well-defined disease states.
B
Provide a multidisciplinary approach to pain manage-
ment in persistent disease states.
B
Recommend psychological treatment for refractory
chronic vulvar pain.
B
Use alternative therapies in the treatment of chronic
gynaecological pelvic pain.
C
Figure 10: assessment and treatment algorithm
gynaecological aspects in chronic pelvic pain
Gynaecological
examination
Ultrasound
Laparoscopy
(see text)
Assessment
Grade A
recommended
Treatment
Grade B
recommended
Laparoscopy to rule out treatable causes
Hormonal therapy in well dened states
Multidisciplinary approach in persistent
disease states
Psychological treatment for refractory
chronic vulvar pain
284 Chronic Pelvic Pain
GASTROINTESTINAL ASPECTS OF CHRONIC PELVIC
PAIN
Recommendations for functional anorectal pain GR
Functional testing is recommended in patients with
anorectal pain.
A
Biofeedback treatment is recommended in patients
with pelvic pain and dyssynergic defecation.
A
Botulinum toxin and electrogalvanic stimulation can
be considered in the chronic anal pain syndrome.
B
Sacral neuromodulation is recommended in the
chronic anal pain syndrome.
C
Inhaled salbutamol is recommended in the intermit-
tent chronic anal pain syndrome.
C
Figure 11: assessment and treatment algorithm for anorectal
pain syndrome
Endoscopy
Pelvic oor
muscle testing
Anorectal
manometry
Rectal balloon
expulsion test
Assessment
Grade A
recommended
MRI-
defecography
Treatment
Grade B
recommended
Other comments
Biofeedback treatment
Botulinum toxine A in women with pelvic pain

Electrogalvanic stimulation
Sacral neuromodulation should be considered
Inhaled salbutamol should be considered in
intermitent anal pain syndrome
285 Chronic Pelvic Pain
Figure 12: diagnosis algorithm for chronic anorectal pain
PERIPHERAL NERVE PAIN SYNDROMES
Recommendations: pudendal neuralgia GR
It is important to rule out confusable diseases. A
If a peripheral nerve pain syndrome is suspected, early
referral should occur to an expert in the field, working
within a multidisciplinary team environment.
B
Imaging and neurophysiology may help with the diag-
nosis, but the gold standard investigation is an image
and nerve locator guided local anaesthetic injection.
B
Neuropathic pain guidelines are well established.
Standard approaches to management of neuropathic
pain should be utalised.
A
yes
* Anorectal manometry
* Balloon expulsion test
* MRI-Defecography
Anorectal pain
syndrome
Specic disease
guidelines
* Biofeedback
* Electro stimulation
Chronic anorectal pain
no
yes no
Refer to specialist
pain management
unit
yes no
Dysfunction present
Endoscopy normal
Tenderness of puborectalis
muscle
286 Chronic Pelvic Pain
Figure 13: assessment and treatment algorithm for peripheral
nerve pain syndrome
SEXOLOGICAL ASPECTS OF CHRONIC PELVIC PAIN
Recommendations: sexological aspects in chronic
pelvic pain
GR
Patients presenting with symptoms suggestive for
chronic pelvic pain syndrome should be screened for
abuse, without suggesting a causal relation with the
pain.
B
The biopsychosocial model should be applied in
the evaluation of the effect of chronic pelvic pain
syndrome on the sexual function of the patient.
B
The biopsychosocial model should be incorporated
in research in the role of chronic pelvic pain in sexual
dysfunction.
B
Offer behavioral strategies to the patient and his/her
partner to cope with sexual dysfunctions.
B
Training of the pelvic floor muscles is recommended
to improve quality of life and sexual function.
B
Extended
neurological
tests
Extended
history on
nature of pain
Standardised
questionnaires
Assessment
Grade A
recommended
Treatment
Grade B
recommended
Refer to an expert when a peripheral nerve
problem is suspected
Imaging may be of help
Neurophysiology may be of help
Treatment is as for any other nerve injury
287 Chronic Pelvic Pain
Figure 14: assessment and treatment algorithm for sexologial
aspects in chronic pelvic pain
PSYCHOLOGICAL ASPECTS OF CHRONIC PELVIC PAIN
Recommendations: psychological aspects of chronic
pelvic pain
GR
Psychological distress is common in pelvic pain in
women, but should be interpreted in the context of
pain.
A
Ask the patient what she thinks may be wrong to
cause pain, to allow the opportunity to inform and
reassure as appropriate.
B
Try psychological interventions in combination with
medical and surgical treatment, or alone.
A
History of
sexual
functioning
History of
negative
experiences
Ask about
abuse
Psychiatric
history
History of
relationship
Assessment
Grade A
recommended
Treatment
Grade B
recommended
Refer to sexologist when sexual dysfunction
or trauma is present
Screen for sexual abuse
Use a bio-psycho-social model in treating
the pain
Oer behavioral strategies to cope with
sexual dysfunctions
Oer partner treatment
Refer for pelvic oor physiotherapy
288 Chronic Pelvic Pain
Figure 15: assessment and treatment algorithm for psycho-
logical aspects of chronic pelvic pain
PELVIC FLOOR FUNCTION AND CHRONIC PELVIC PAIN
Recommendations: pelvic floor function GR
The use of the ICS classification on pelvic floor muscle
function and dysfunction is recommended.
A
In patients with chronic pelvic pain syndrome it is
recommended to actively look for the presence of
myofascial trigger points.
B
Apply pelvic floor muscle treatment as first line treat-
ment in patients with chronic pelvic pain syndrome.
B
In patients with an overactive pelvic floor biofeedback
is recommended as therapy adjuvant to muscle exer-
cises.
A
When myofascial triggerpoints are found treatment by
pressure or needling is recommended.
A
Psychological
history
Investigate
pain-related
beliefs and
behavior
Assessment
Grade A
recommended
Treatment
Grade B
recommended
Interpret psychological distress in the context
of pain
Psychological interventions as adjuvant to
other modalities
Ask the patient what he or she believes may be
the problem that causes the pain
289 Chronic Pelvic Pain
Figure 16: assessment and treatment pelvic floor function
GENERAL TREATMENT OF CHRONIC PELVIC PAIN
Recommendations: medical and interventional treatment
of chronic pelvic pain
Agent Pain Type LE GR Comment
Paracetamol Somatic pain 1a A Evidence
based on
arthritic pain
with good
benefit
NSAIDs Pelvic pain
with inflam-
matory
process (e.g.
dysmenor-
rhoea)
1a A Good evi-
dence for their
use
Palpation of
the muscles
Testing of
pelvic oor
function
Pelvic oor
muscle EMG
Test for
myofascial
triggerpoints
Standardised
questionnaires
Assessment
Grade A
recommended
History of all
the involved
organs
Treatment
Grade B
recommended
Other comments
Use the International Continence Society
classication of dysfunction
Use biofeedback in combination with muscle
exercises
Look actively for the presence of myofascial
trigger points
Apply pelvic oor muscle therapy as rst line
treatment
Treat myofascial triggerpoints using pressure
or needling
The role and options of a physiotherapist may
dier between countries
290 Chronic Pelvic Pain
Antidepressants
including tricyclic
antidepressants,
duloxetine and
venlafaxine
Neuropathic
pain
1a A Effective.
No specific
evidence for
chronic pelvic
pain
Anticonvulsants
gabapentin, pre-
gabalin
Neuropathic
pain, fibro-
myalgia
1a A Effective
Gabapentin Women with
chronic pel-
vic pain
2b B Effective
Topical capsaicin Neuropathic
pain
1a A Some evi-
dence of
benefit
Opioids Chronic non-
malignant
pain
1a A Beneficial in a
small number
of patients
Nerve blocks 3 C Have a role as
part of a broad
management
plan
TENS 1b B There is no
good evi-
dence for or
against the
use of TENS.
Data covered
chronic pain
not just CPP
and was insuf-
ficient regard-
ing long-term
treatment
effects.
291 Chronic Pelvic Pain
Neuromodulation Pelvic pain 3 C Role devel-
oping with
increasing
research.

Figure 17: algorithm for general analgesic treatment of
chronic pelvic pain
General
history
Medications
used
Allergic
reactions
Use of alcohol
Assessment
Grade A
recommended
Daily activities
that will be
aected
Treatment
Grade B
recommended
Other comments
Paracetamol in somatic pain
NSAIDs when inammation is present
Anticonvulsants in neuropathic pain
Topical Capsaicin in neuropathic pain
Antidepressants (including TCA) in
neuropathic pain
Nerve blocks as part of a broad management
plan
[C]
Neuromodulation may become an option,
increasing research

[C]
Opiods in chronic non-malignant pain
Gabapentin in women with CPP
292 Chronic Pelvic Pain
Figure 18: algorithm for general management
This short booklet text is based on the more comprehensive EAU
guidelines (ISBN 978-90-79754-83-0), available to all members of the
European Association of Urology at their website,
http://www.uroweb.org.
Pain described in neuropathic or
central pain terms
yes no
First-line management trial using
1. Amitriptyline
2. Gabapentin
Adequate
analgesia:
review regularly
sustained eect:
consider dose
reduction
Adequate
analgesia:
discharge back to
primary care
physician
Inadequate
response:
refer to specialist
pain management
unit
Inadequate
response:
consider adding
another rst line
agent
rotate agents
Still inadequate:
refer to specialist
pain management
unit
Simple analgesics
Review Review
Alternatives:
1. Nortriptyline or Imipramine
2. Pregabalin
293 Urolithiasis
GUIDELINES ON UROLITHIASIS
(Update March 2013)
C. Trk (chair), T. Knoll (vice-chair), A. Petrik, K. Sarica, C. Seitz,
A. Skolarikos, M. Straub
Classification of stones
Urinary stones can be classified according to the following
aspects: stone size, stone location, X-ray characteristics
of stone, aetiology of stone formation, stone composition
(mineralogy), and risk group for recurrent stone formation
(Tables 1-3).
Table 1: X-ray characteristics
Radiopaque Poor radiopaque Radiolucent
Calcium oxalate
dihydrate
Magnesium
ammonium phos-
phate
Uric acid
Calcium oxalate
monohydrate
Apatite Ammonium urate
Calcium phos-
phates
Cystine Xanthine
2,8-dihydroxyade-
nine
Drug-stones
294 Urolithiasis
Table 2: Stones classified according to their aetiology
Non infection
stones
Infection
stones
Genetic
stones
Drug stones
Calcium
oxalates
Magnesium
ammonium
phosphate
Cystine e.g. indinavir
(see extended
document)
Calcium
phosphates
Carbonate
apatite
Xanthine
Uric acid Ammonium
urate
2,8-dihydroxy-
adenine
Table 3: Stones classified by their composition
Chemical composition Mineral
Calcium oxalate monohydrate whewellite
Calcium-oxalate-dihydrate wheddelite
Uric acid dihydrate uricite
Ammonium urate
Magnesium ammonium phosphate struvite
Carbonate apatite (phosphate) dahllite
Calcium hydrogenphosphate brushite
Cystine
Xanthine
2,8-dihydroxyadenine
Drug stones
Risk groups for stone formation
The risk status of a stone former is of particular interest as it
defines both probability of recurrence or (re)growth of stones
and is imperative for pharmacological treatment.
295 Urolithiasis
Table 4: High risk stone formers
General factors
Early onset of urolithiasis in life (especially children and
teenagers)
Familial stone formation
Brushite containing stones (calcium hydrogen phosphate;
CaHPO
4
.2H
2
O)
Uric acid and urate containing stones
Infection stones
Solitary kidney (The solitary kidney itself does not present an
increased risk of stone formation, but prevention of stone
recurrence is more important)
Diseases associated with stone formation
Hyperparathyroidism
Nephrocalcinosis
Gastrointestinal diseases or disorders (e.g. jejuno-ileal
bypass, intestinal resection, Crohns disease, malabsorptive
conditions, enteric hyperoxaluaria after urinary diversion
and bariatric surgery)
Sarcoidosis
Genetically determined stone formation
Cystinuria (type A, B, AB)
Primary hyperoxaluria (PH)
Renal tubular acidosis (RTA) type I
2,8-dihydroxyadenine
Xanthinuria
Lesch-Nyhan-Syndrome
Cystic fibrosis
Drugs associated with stone formation (see Chapter 11
extended text)
Anatomical abnormalities associated with stone formation
Medullary sponge kidney (tubular ectasia)
296 Urolithiasis
UPJ obstruction
Calyceal diverticulum, calyceal cyst
Ureteral stricture
Vesico-uretero-renal reflux
Horseshoe kidney
Ureterocele
DIAGNOSIS
Diagnostic imaging
Standard evaluation of a patient includes taking a detailed
medical history and physical examination. The clinical diagno-
sis should be supported by appropriate imaging.
Recommendation LE GR
With fever or solitary kidney, and when diagno-
sis is doubtful, immediate imaging is indicated.
4 A*
*Upgraded following panel consensus.
If available, ultrasonography should be used as the primary
diagnostic imaging tool although pain relief, or any other
emergency measures should not be delayed by imaging
assessments. KUB should not be performed if non-contrast
enhanced computed tomography (NCCT) is considered, but
KUB can differentiate between radiolucent and radiopaque
stones and serve for comparison during follow-up.
Evaluation of patients with acute flank pain
Recommendation LE GR
NCCT should be used to confirm stone diagno-
sis in patients with acute flank pain, because it
is superior to IVU.
1a A
297 Urolithiasis
Some drug stones like indinavir stones are not detectable on
NCCT.
Recommendation LE GR
A renal contrast study (enhanced CT or IVU) is
indicated when planning treatment for renal
stones.
3 A*
*Upgraded following panel consensus.
Biochemical work-up
Each emergency patient with urolithiasis needs a succinct
biochemical work-up of urine and blood besides imaging
studies; no difference is made between high- and low-risk
patients.
Recommendations: Basic analysis emergency stone patient
Urine GR
Urinary sediment/dipstick test out of spot urine sam-
ple for: red cells / white cells / nitrite / urine pH level
by approximation.
A*
Urine culture or microscopy. A
Blood
Serum blood sample creatinine / uric acid / ionized
calcium / sodium / potassium / CRP.
A*
Blood cell count. A*
If intervention is likely or planned: Coagulation test
(PTT and INR).
A*
*Upgraded following panel consensus.
Examination of sodium, potassium, CRP, and blood coagula-
tion time can be omitted in the non-emergency stone patient.
Patients at high risk for stone recurrences should undergo a
298 Urolithiasis
more specific analytical programme (see section on Metabolic
Evaluation below).
Analysis of stone composition should be performed in all first-
time stone formers (GR: A) and will need redoing if changes
are expected. The preferred analytical procedures are:
X-ray diffraction (XRD)
Infrared spectroscopy (IRS)
Wet chemistry is generally deemed to be obsolete.
Acute treatment of a patient with renal colic
Pain relief is the first therapeutic step in patients with an
acute stone episode.
Recommendations for pain relief during and
prevention of recurrent renal colic
LE GR
First choice: start with an NSAID, e.g.
diclofenac*, indomethacin or ibuprofen.**
1b A
Second choice: hydromorphine, pentazocine
and tramadol.
4 C
Use a-blockers to reduce recurrent colic. 1a A
GFR = glomerular filtration rate; NSAID = non-steroidal anti-
inflammatory drug.
*Caution: Diclofenac sodium affects GFR in patients with
reduced renal function, but not in patients with normal renal
function (LE: 2a).
** Recommended to counteract recurrent pain after renal
colic. (see extended document section 5.3)
If analgesia cannot be achieved medically, drainage, using
stenting or percutaneous nephrostomy, or stone removal,
should be performed.
Management of sepsis in the obstructed kidney
The obstructed, infected kidney is a urological emergency.
299 Urolithiasis
Recommendations LE GR
For sepsis with obstructing stones, the collect-
ing system should be urgently decompressed,
using either percutaneous drainage or ureteral
stenting.
1b A
Definitive treatment of the stone should be
delayed until sepsis is resolved.
1b A
In exceptional cases, with severe sepsis and/or the forma-
tion of abscesses, an emergency nephrectomy may become
necessary.
Recommendations - Further Measures
GR
Collect urine for antibiogram following decompres-
sion.
A*
Start antibiotics immediately thereafter (+ intensive
care if necessary).
Revisit antibiotic treatment regimen following antibio-
gram findings.
* Upgraded based on panel consensus.
Stone relief
When deciding between active stone removal and conserva-
tive treatment using MET, it is important to consider the
individual circumstances of a patient that may affect treat-
ment decisions.
300 Urolithiasis
Observation of ureteral stones
Recommendations LE GR
In patients with newly diagnosed ureteral
stones < 10 mm, and if active stone removal is
not indicated, observation with periodic evalua-
tion is optional initial treatment.
1a A
Such patients may be offered appropriate medi-
cal therapy to facilitate stone passage during
observation*.
*see also Section MET.
Observation of kidney stones
It is still debatable whether kidney stones should be treated,
or whether annual follow-up is sufficient for asymptomatic
caliceal stones that have remained stable for 6 months.
Recommendations GR
Kidney stones should be treated in case of growth,
formation of de novo obstruction, associated infec-
tion, and acute and/or chronic pain.
A
Comorbidity and patient preference need to be taken
into consideration when making treatment decisions.
C
If kidney stones are not treated, periodic evaluation is
needed.
A
* Upgraded following panel consensus.
Medical expulsive therapy (MET)
For patients with ureteral stones that are expected to pass
spontaneously, NSAID tablets or suppositories and a-blockers
may help to reduce inflammation and the risk of recurrent
pain.
301 Urolithiasis
Recommendations for MET LE GR
For MET, a-blockers are recommended. A
Patients should be informed about the attend-
ant risks of MET, including associated drug side
effects, and should be informed that it is admin-
istered as off-label**.
A*
Patients, who elect for an attempt at sponta-
neous passage or MET, should have well-con-
trolled pain, no clinical evidence of sepsis, and
adequate renal functional reserve.
A
Patients should be followed to monitor stone
position and to assess for hydronephrosis.
4 A*
*Upgraded following panel consensus.
** MET using a-blockers in children and during pregnancy can-
not be recommended due to the limited data in this specific
population.
Statements
LE
There is good evidence that MET accelerates spon-
taneous passage of ureteral stones and fragments
generated with SWL limits pain.
1
No recommendation for the use of corticosteroids in
combination with a-blockers in MET can be made, due
to limited data.
1b
Chemolytic dissolution of stones
Oral or percutaneous irrigation chemolysis of stones can be
a useful first-line therapy or an adjunct to SWL, PNL, URS, or
open surgery to support elimination of residual fragments.
However, its use as first-line therapy may take weeks to be
effective.
302 Urolithiasis
Percutaneous irrigation chemolysis
Recommendations GR
In percutaneous chemolysis, at least two nephrosto-
my catheters should be used to allow irrigation of the
renal collecting system, while preventing chemolytic
fluid draining into the bladder and reducing the risk of
increased intrarenal pressure*.
A
Pressure- and flow-controlled systems should be used
if available.
* Alternatively, one nephrostomy catheter with a JJ stent and
bladder catheter can serve as a through-flow system pre-
venting high pressure.
Methods of percutaneous irrigation chemolysis
Percutaneous irrigation chemolysis is rarely used; it may be
an option for infection stones (using 10% Hemiacidrin at a pH
of 3,5 -4) and for uric acid and cystine stones (using THAM
[Trihydroxymethylaminomethan], 0.3 or 0.6mol/L, pH 8.5-9.0).
For uric acid stones oral chemolysis is preferred.
Oral chemolysis
Oral chemolitholysis is efficient for uric acid calculi only. The
urine pH should be adjusted to between 6.5 and 7.2.
Recommendations GR
The dosage of alkalising medication must be modified
by the patient according to the urine pH, which is a
direct consequence of the alkalising medication.
A
Dipstick monitoring of urine pH by the patient is
required at regular intervals during the day. Morning
urine must be included.
A
303 Urolithiasis
Careful monitoring of radiolucent stones during/after
therapy is imperative.
A
The physician should clearly inform the patient of the
significance of compliance.
A
SWL
The success rate for SWL will depend on the efficacy of the
lithotripter and on:
size, location (ureteral, pelvic or calyceal), and composition
(hardness) of the stones;
patients habitus;
performance of SWL.
Contraindications of SWL
Contraindications to the use of SWL are few, but include:
pregnancy;
bleeding diatheses;
uncontrolled urinary tract infections (UTIs);
severe skeletal malformations and severe obesity, which
prevent targeting of the stone;
arterial aneurism in the vicinity of the stone;
anatomical obstruction distal of the stone.
Stenting prior to SWL
Kidney stones
A JJ stent reduces the risk of renal colic and obstruction, but
does not reduce formation of steinstrasse or infective compli-
cations.
Recommendation - stenting & SWL LE GR
Routine stenting is not recommended as part of
SWL treatment of ureteral stones.
1b A
304 Urolithiasis
Best clinical practice (best performance)
Pacemaker
Patients with a pacemaker can be treated with SWL, provided
that appropriate technical precautions are taken; patients
with implanted cardioverter defibrillators must be managed
with special care (firing mode temporarily reprogrammed dur-
ing SWL treatment). However, this might not be necessary
with new-generation lithotripters.
Recommendation - Shock wave rate LE GR
The optimal shock wave frequency is 1.0
(to 1.5) Hz.
1a A
Number of shock waves, energy setting and repeat treatment
sessions
The number of shock waves that can be delivered at each
session depends on the type of lithotripter and shockwave
power.
Starting SWL on a lower energy setting with step-wise
power (and SWL sequence) ramping prevents renal injury.
Clinical experience has shown that repeat sessions are
feasible (within 1 day for ureteral stones).
Procedural control
Results of treatment are operator dependent. Careful imaging
control of localisation will contribute to outcome quality.
Pain control
Careful control of pain during treatment is necessary to limit
pain-induced movements and excessive respiratory excur-
sions.
Antibiotic prophylaxis
No standard prophylaxis prior to SWL is recommended.
305 Urolithiasis
Recommendation LE GR
In case of infected stones or bacteriuria,
antibiotics should be given prior to SWL.
4 C
Medical expulsive therapy (MET) after SWL can expedite
expulsion and enhance stone-free rates.
Percutaneous nephrolitholapaxy (PNL)
Recommendation GR
Ultrasonic, ballistic and Ho:YAG devices are recom-
mended for intracorporeal lithotripsy using rigid
nephroscopes.
A*
When using flexible instruments, the Ho:YAG laser is
currently the most effective device available.
* Upgraded following panel consensus.
Best clinical practice
Contraindications:
all contraindications for general anaesthesia apply;
untreated UTI;
atypical bowel interposition;
tumour in the presumptive access tract area;
potential malignant kidney tumour;
pregnancy.
Pre-operative recommendation - imaging GR
Preprocedural imaging, including contrast medium
where possible or retrograde study when starting the
procedure, is mandatory to assess stone comprehen-
siveness, view the anatomy of the collecting system,
and ensure safe access to the kidney stone.
A*
* Upgraded based on panel consensus.
306 Urolithiasis
Positioning of the patient: prone or supine?
Traditionally, the patient is positioned prone for PNL,
supine position is also possible, showing advantages in
shorter operating time, the possibility of simultaneous ret-
rograde transurethral manipulation, and easier anaesthesia.
Disadvantages are limited manoeuvrability of instruments
and the need of appropriate equipment.
Nephrostomy and stents after PNL
Recommendation LE GR
In uncomplicated cases, tubeless (without
nephrostomy tube) or totally tubeless (without
nephrostomy tube and without ureteral stent)
PNL procedures provide a safe alternative.
1b A
Ureterorenoscopy (URS)
(including retrograde access to renal collecting system)
Best clinical practice in URS
Before the procedure, the following information should be
sought and actions taken (LE: 4):
Patient history;
physical examination (i.e. to detect anatomical and con-
genital abnormalities);
thrombocyte aggregation inhibitors/anticoagulation
(anti-platelet drugs) treatment should be discontinued.
However, URS can be performed in patients with bleeding
disorders, with only a moderate increase in complications;
imaging.
Recommendation GR
Short-term antibiotic prophylaxis should be adminis-
tered.
A*
307 Urolithiasis
Contraindications
Apart from general considerations, e.g. with general anaes-
thesia or untreated UTIs, URS can be performed in all patients
without any specific contraindications.
Access to the upper urinary tract
Most interventions are performed under general anaesthesia,
although local or spinal anaesthesia are possible. Intravenous
sedation with miniaturized instruments is especially suitable
for female patients with distal ureteral stones. Antegrade URS
is an option for large, impacted proximal ureteral calculi.
Safety aspects
Fluoroscopic equipment must be available in the operating
room. If ureteral access is not possible, the insertion of a
JJ stent followed by URS after a delay of 7-14 days offers an
appropriate alternative to dilatation.
Recommendation GR
Placement of a safety wire is recommended. A*
*Upgraded following panel consensus.
Ureteral access sheaths
Hydrophilic-coated ureteral access sheaths (UAS), can be
inserted via a guide wire, with the tip placed in the proximal
ureter. Ureteral access sheaths allow easy multiple access to
the upper urinary tract and therefore significantly facilitate
URS. The use of UAS improves vision by establishing a con-
tinuous outflow, decrease intrarenal pressure and potentially
reduce operating time.
Stone disintegration and extraction
The aim of endourological intervention is complete stone
removal. Smash and go strategies should be limited to the
treatment of large renal stones. For flexible URS (RIRS) only
308 Urolithiasis
baskets made of Nitinol are suitable.
Recommendation LE GR
Stone extraction using a basket without endo-
scopic visualisation of the stone (blind basket-
ing) should not be performed.
4 A*
Ho:YAG laser lithotripsy is the preferred method
for (flexible) URS.
3 B
*Upgraded following panel consensus.
Stenting before and after URS
Pre-stenting facilitates ureteroscopic management of stones,
improves the stone-free rate, and reduces complications.
Following URS, stents should be inserted in patients who are
at increased risk of complications.
Recommendation LE GR
In uncomplicated URS, a stent need not be
inserted.
1a A
An a-blocker can reduce stent-related symp-
toms
1a
Open surgery
Most stones should be approached primarily with PNL, URS,
SWL, or a combination of these techniques. Open surgery may
be a valid primary treatment option in selected cases.
Indications for open surgery:
Complex stone burden
Treatment failure of SWL and/or PNL, or URS
Intrarenal anatomical abnormalities: infundibular steno-
sis, stone in the calyceal diverticulum (particularly in an
anterior calyx), obstruction of the ureteropelvic junction,
309 Urolithiasis
stricture if endourologic procedures have failed or are not
promising
Morbid obesity
Skeletal deformity, contractures and fixed deformities of
hips and legs
Comorbidity
Concomitant open surgery
Non-functioning lower pole (partial nephrectomy), non-
functioning kidney (nephrectomy)
Patient choice following failed minimally invasive proce-
dures; the patient may prefer a single procedure and avoid
the risk of needing more than one PNL procedure
Stone in an ectopic kidney where percutaneous access
and SWL may be difficult or impossible
For the paediatric population, the same considerations
apply as for adults.
Laparoscopic surgery
Indications for laparoscopic kidney-stone surgery include:
complex stone burden;
failed previous SWL and/or endourological procedures;
anatomical abnormalities;
morbid obesity;
nephrectomy in case of non-functioning kidney.
Indications for laparoscopic ureteral stone surgery include:
large, impacted stones;
multiple ureteral stones;
in cases of concurrent conditions requiring surgery;
when other non-invasive or low-invasive procedures have
failed.
If indicated, for upper ureteral calculi, laparoscopic urolithomy
has the highest stone-free rate compared to URS and SWL
(LE: 1a).
310 Urolithiasis
Recommendations LE GR
Laparoscopic or open surgical stone removal
may be considered in rare cases where SWL,
URS, and percutaneous URS fail or are unlikely
to be successful.
3 C
When expertise is available, laparoscopic sur-
gery should be the preferred option before pro-
ceeding to open surgery. An exception is com-
plex renal stone burden and/or stone location.
3 C
For ureterolithotomy, laparoscopy is recom-
mended for large impact stones or when endo-
scopic lithotripsy or SWL have failed.
2 B
Indication for active stone removal and selection of
procedure
Ureter:
stones with a low likelihood of spontaneous passage;
persistent pain despite adequate pain medication;
persistent obstruction;
renal insufficiency (renal failure, bilateral obstruction, sin-
gle kidney).
Kidney:
stone growth;
stones in high-risk patients for stone formation;
obstruction caused by stones;
infection;
symptomatic stones (e.g. pain, haematuria);
stones > 15 mm;
stones < 15 mm if observation is not the option of choice;
patient preference (medical and social situation);
comorbidity;
choice of treatment.
The suspected stone composition might influence the choice
of treatment modality.
311 Urolithiasis
Recommendations GR
For asymptomatic caliceal stones in general, active
surveillance with an annual follow-up of symptoms
and stone status (KUB, ultrasonography [US], NCCT)
is an option for 2-3 years, whereas intervention should
be considered after this period provided patients are
adequately informed.
C
Observation might be associated with a greater risk of
necessitating more invasive procedures.
STONE REMOVAL
Recommendations GR
Urine culture or urinary microscopy is mandatory
before any treatment is planned and urinary infection
should be treated ahead of stone removal.
A*
Anticoagulation therapy including salicylates should
be stopped before stone removal.
B
If intervention for stone removal is essential and sali-
cylate therapy should not be interrupted, retrograde
URS is the preferred treatment of choice.
*Upgraded based on panel consensus.
Radiolucent uric acid stones, but not sodium urate or ammo-
nium urate stones, can be dissolved by oral chemolysis.
312 Urolithiasis
Selection of procedure for active removal of renal
stones**
Fig. 1: Treatment algorithm for renal calculi
* Flexible URS is used less as first-line therapy for renal stones
> 1.5 cm.
** The ranking of the recommendations reflects a panel
majority vote.
*** see Table 19 extended document
Kidney stone
(all but lower pole stone 10-20 mm)
Lower pole stone
> 20 mm and < 10 mm: like above
1. PNL
2. RIRS or SWL
SWL or Endourology*
SWL or Endourology
1. SWL or RIRS
2. PNL
1. Endourology
2. SWL
10-20 mm
Favourable
factors for
SWL***
< 10 mmm
> 20 mm
Yes
No
10-20 mm
313 Urolithiasis
Selection of procedure for active stone removal of
ureteral stones (GR: A*)
Stone location and size First choice Second choice
Proximal ureter < 10 mm SWL URS
Proximal ureter > 10 mm URS (retrograde or antegrade)
or SWL
Distal ureter < 10 mm URS or SWL
Distal ureter > 10 mm URS SWL
*Upgraded following panel consensus.
Recommendation GR
Percutaneous antegrade removal of proximal ureteral
stones is an alternative when SWL is not indicated
or has failed, and when the upper urinary tract is not
amenable to retrograde URS.
A
Steinstrasse
Steinstrasse occurs in 4% to 7% of cases after SWL, the major
factor in steinstrasse formation is stone size.
Recommendations LE GR
Medical expulsion therapy increases the stone
expulsion rate of steinstrasse.
1b A
PCN is indicated for steinstrasse associated
with UTI/fever.
4 C
SWL is indicated for steinstrasse when large
stone fragments are present.
4 C
Ureteroscopy is indicated for symptomatic
steinstrasse and treatment failure.
4 C
314 Urolithiasis
Residual stones
Recommendations LE GR
Identification of biochemical risk factors and
appropriate stone prevention is particularly
indicated in patients with residual fragments or
stones.
1b A
Patients with residual fragments or stones
should be followed up regularly to monitor dis-
ease course.
4 C
After SWL and URS, MET is recommended using
an a-blocker to improve fragment clearance.
1a A
For well-disintegrated stone material in the
lower calix, an inversion therapy with simul-
taneous mechanical percussion manoeuvre
under enforced diuresis may facilitate stone
clearance.
1a B
The indication for active stone removal and selection of the
procedure is based on the same criteria as for primary stone
treatment and also includes repeat SWL.
Management of urinary stones and related problems
during pregnancy
Recommendations LE GR
US is the method of choice for practical and
safe evaluation of pregnant women.
1a A
Conservative management should be the first-
line treatment for all non-complicated cases
of urolithiasis in pregnancy (except those that
have clinical indications for intervention).
A
315 Urolithiasis
If intervention becomes necessary, placement
of an internal stent, percutaneous nephros-
tomy, or ureteroscopy are treatment options.
3
URS is a reasonable alternative to avoid long-
term stenting/drainage.
2a
Regular follow-up until final stone removal is
necessary due to higher encrustation tendency
of stents during pregnancy.
Pregnancy remains an absolute contraindication for SWL.
Management of stone problems in children
Spontaneous passage of a stone and of fragments after SWL
is more likely to occur in children than in adults (LE: 4). For
paediatric patients, the indications for SWL and PNL are
similar to those in adults, however they pass fragments more
easily. Children with renal stones with a diameter up to 20 mm
(~300 mm
2
) are ideal candidates for SWL.
Recommendations GR
Ultrasound evaluation is the first choice for imaging in
children and should include the kidney, filled bladder
and adjoining portions of the ureter.
A*
If US does not provide the required information, KUB
radiography (or NCCT) should be performed.
B
In all paediatric patients all efforts should be made to
collect stone material for analysis, followed by
complete metabolic evaluation.
A
*Upgraded from B following panel consensus.
316 Urolithiasis
Table 5: Stones in exceptional situations
Caliceal diverticulum
stones
SWL, PNL (if possible) or RIRS
(retrograde intrarenal surgery
via flexible ureteroscopy).
Can also be removed using
laparoscopic retroperitoneal
surgery.
Patients may become asympto-
matic due to stone disintegra-
tion (SWL) whilst well-disinte-
grated stone material remains in
the original position.
Horseshoe kidneys Can be treated in line with
the stone treatment options
described above.
Passage of fragments after SWL
might be poor.
Stones in pelvic kidneys SWL, RIRS or laparoscopic sur-
gery
For obese patients, the options
are SWL, PNL, RIRS or open
surgery
Stones in transplanted
kidneys
PNL, (flexible) URS, SWL.
Metabolic evaluation based on
stone analysis
Stones formed in urinary
division
Individual management
necessary.
For smaller stones SWL is
effective.
PNL and antegrade flexible URS
frequently used .
317 Urolithiasis
Stones formed in a conti-
nent reservoir
Present a varied and often dif-
ficult problem.
Each stone problem must be
considered and treated individu-
ally.
Stones in patients with
neurogenic bladder dis-
order
All methods apply based on indi-
vidual situation.
Careful patient follow up and
preventive strategies are impor-
tant.
In myelomeningocele-patients,
latex allergy is common, appro-
priate measures needed.
Patients with obstruc-
tion of the ureteropelvic
junction which needs cor-
rection
PNL followed by percutaneous
endopyelotomy or open/laparo-
scopic surgery, or URS together
endopyelothomy with Ho:YAG.
Incision with an Acucise balloon
catheter might be considered,
provided the stones can be
prevented from falling into the
pelvo-ureteral incision.
318 Urolithiasis
Metabolic evaluation and recurrence prevention
Stone prevention is based on a reliable stone analysis and
basic analysis as mentioned above. Every patient should be
assigned to the low- or high risk group for stone formation.
For both groups general preventive measures apply:
Fluid intake (drinking
advice)
Fluid amount: 2.5-3.0 L/day
Circadian drinking
Neutral pH beverages
Diuresis: 2.0-2.5 L/day
Specific weight of urine: < 1010
Nutritional advice for
a balanced diet
Balanced diet*
Rich in vegetable and fibre
Normal calcium content: 1-1.2 g/day
Limited NaCl content: 4-5 g/day
Limited animal protein content: 0.8-
1.0 g/kg/day
Lifestyle advice to
normalise general
risk factors
BMI: 18-25 kg/m
2
(adults)
Stress limitation measures
Adequate physical activity
Balancing of excessive fluid loss
For patients assigned to the high risk group of stone formers
specific laboratory analysis of blood and urine including two
consecutive 24-hour urine samples are necessary. For the
specific metabolic work-up, the patient should stay on a self-
determined diet under normal daily conditions and should ide-
ally be stone free for at least 20 days, better 3 months. These
findings are the basis for further recommendations:
319 Urolithiasis
Recommendations on specific diet LE GR
Hyperoxaluria Oxalate restriction 2b B
High sodium excretion Restricted intake of
salt
1b A
Small urine volume Increased fluid intake 1b A
Urea level indicating a
high intake of animal
protein
Avoid excessive intake
of animal protein
1b A
Recommendations for specific pharmacological treatment
Urinary risk factor Suggested treatment LE GR
Hypercalciuria Thiazide + potassium
citrate
1a A
Hyperoxaluria Oxalate restriction 2b A
Enteric hyperoxaluria Potassium citrate 3-4 C
Calcium supplement 2 B
Oxalate absorption 3 B
Hypocitraturia Potassium citrate 1b A
Calcium oxalate stones
(Hyperparathyreoidism excluded by blood examination)
320 Urolithiasis
Fig. 2: Diagnostic and therapeutic algorithm for calcium
oxalate stones
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321 Urolithiasis
Calcium phosphate stones
Fig. 3: Diagnostic and therapeutic algorithm for calcium
phosphate stones

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322 Urolithiasis
Hyperparathyroidism
Elevated levels of ionized calcium in serum (or total calcium
and albumin) require assessment of intact parathyroid hor-
mone (PTH) to confirm or exclude suspected hyperparathy-
roidism (HPT). Primary HTP can only be cured by surgery.
Uric acid and ammonium urate stones
Fig 4: Diagnostic and therapeutic algorithm for uric acid and
ammonium urate stones.
Urate containing stones
Ammonium urate stone
Urid acid stone
Basic evaluation Basic evaluation
Urine
pH > 6.5 Uric acid arrest
Urine pH < 6
Alcaline citrate
9-12 g/d
2
Or
Sodium
bicarbonate
1.5 g tid
L-methionine
200-500 mg tid
Target urine-pH
5.8-6.2
Correction of
factors
predisposing
amm.urate stone
formation
Dose depends on
targeted urine pH
Prevention
urine pH 6.2-6.8
Chemolytholisis
urine pH 6.5-7.2
Allopurinol
100-300 mg/d
UTI
Antibiotics
> 4.0 mmol/d
> 4.0 mmol/d
and
Hyperuricemia
> 380 mol
Allopurinol
100 mg/d
Hyperuricosuria
323 Urolithiasis
Fig 5: Metabolic management of cystine stones.
Basic evaluation
Appropriate hydration
with > 3.5 L/d in adults and
1.5 L/m2 body surface in
children
AND
Adjust urine pH
between 7.5. and 8.5
with
alkaline citrates or
sodium bicarbonate
Cystine excretion
< 3 mmol/d
possible add. treatment
with Tiopronin
(depending on recurrence)
Cystine excretion
> 3 mmol/d
Additional treatment with
Tiopronin 250 mg/d up to
2000 mg/d max. dos
Cystine stones
324 Urolithiasis
Struvite and infection stones
Recommendations Therapeutic measure LE GR
Surgical removal of the stone material as com-
pletely as possible.
3,4 A*
Short-term antibiotic course. 3 B
Long-term antibiotic course. 3 B
Urinary acidification: ammonium chloride;
1 g, 2 - 3 x daily.
3 B
Urinary acidification: methionine;
200-500 mg, 1 - 3 x daily.
3 B
Urease inhibition. 1b A
Cystine stones
Therapeutic measures LE GR
Urine dilution
High fluid intake recommended so that 24-h urine
volume exceeds 3 L.
Intake should be 150 mL/h.
3 B
Alkalinisation
For cystine excretion < 3 mmol/day: potassium
citrate 310 mmol 2 or 3 times daily, to achieve
pH > 7.5.
3 B
Complex formation with cystine
For patients with cystine excretion > 3 mmol/day,
or when other measures are insufficient:
tiopronin, 2502000 mg/day.
Captopril, 75150 mg/day, remains a second-line
option if tiopronin is not feasible or unsuccessful.
3 B
325 Urolithiasis
2,8-dihydroyadenine stones and xanthine stones
Both stone types are rare. In principle, diagnosis and specific
prevention is similar to that of uric acid stones.
Drug stones
Drug stones are induced by pharmacological treatment. Two
types exist:
stones formed by crystallised compounds of the drug;
stones formed due to unfavourable changes in urine com-
position under drug therapy.
Treatment includes general preventive measures and the
avoidance of the respective drugs
Investigating a patient with stones of unknown composition
Investigation Rationale for investigation
Medical history Stone history (former stone events,
family history)
Dietary habits
Medication chart
Diagnostic imaging Ultrasound in case of a suspected
stone
Unenhanced helical CT
(Determination of the Houndsfield
unit provides information about the
possible stone composition)
Blood analysis Creatinine
Calcium (ionized calcium or total
calcium + albumin)
Uric acid
326 Urolithiasis
Urinalysis Urine pH profile (measurement
after each voiding, minimum 4
daily)
Dipstick test: leucocytes, eryth-
rocytes, nitrite, protein, urine pH,
specific weight
Urine culture
Microscopy of urinary sediment
(morning urine)
Cyanide nitroprusside test (cystine
exclusion)
Further examinations depend on the results of the investiga-
tions listed above.
This short booklet text is based on the more comprehensive EAU
guidelines (ISBN 978-90-79754-71-7) available to all members of the
European Association of Urology at their website,
http://www.uroweb.org.
327 Renal Transplantation
GUIDELINES ON
RENAL TRANSPLANTATION
(Text update March 2009)
G. Karam (chair), T. Klble, A. Alcaraz, F.T. Aki, K. Budde,
U. Humke, F. Kleinclauss, G. Nicita, J.O. Olsburgh, C. Ssal
Introduction
As attitudes and practice to renal transplantation (RT) vary
significantly the Guidelines provide general guidance only.
Kidney donation
There is a widening gap between donation and demand for
kidney transplants, with not enough deceased donors. There
is, however, a clear trend towards an increase in living-donor
transplants.
Recommendations for increasing donation GR
Deceased donors
In all countries without presumed consent law,
increase efforts to recruit donors through an opting-in
register or by carrying donor cards.
C
Greater use of non-heart-beating donors (NHBD)
should be made. Create policies for recently dead
admissions to casualty departments which may be
used as NHBDs.
B
Use of carefully selected donors > 60 years should be
encouraged as a continuing source of deceased-donor
kidneys.
B
Organs from deceased donors > 70 years should be
individually evaluated.
B
Living donors
328 Renal Transplantation
Organ donation should be considered a charitable gift.
Society can express gratitude to organ donors for their
gift (e.g. Medal of Honour, donor insurance).
C
Explore living donation when a patient first presents
with end-stage renal disease.
C
Decisions about multiple renal artery or grafts with
anatomical anomalies should be made on an individual
basis.
C
Laparoscopic nephrectomy offers similar results (com-
plications, graft function and graft survival) compared
to open nephrectomy, with less post-operative morbid-
ity, shorter convalescence and better cosmetic results.
A
Laparoscopic nephrectomy increases the number of
people willing to donate.
C
Paired kidney exchange, if permitted by national law. C
Kidney donor selection and refusal criteria
The physical condition of the donor, especially of the organ
to be donated, is more important than age. Important risk
factors for organ failure are a prolonged history of diabetes
mellitus or serious hypertension with retinal vascular damage.
Factors for excluding potential donors or for considering sin-
gle- rather than multi-organ donations include previous myo-
cardial infarction, coronary bypass angina, severe systemic
vascular disease and long-lasting hypotension, oliguria, and a
long period in intensive care.
The potential donor should be assessed for human immu-
nodeficiency virus-1, -2 (HIV-1, HIV-2), hepatitis C virus (HCV)
and hepatitis B surface antigen (HBsAg), anti-hepatitis B core
(anti-HBc) antibody, acute hepatitis (liver enzymes), cytome-
galovirus (CMV), Epstein-Barr virus if the recipient is paediat-
ric, active syphilis, other viral infections, sepsis, tuberculosis,
infections of unknown aetiology, and a family history (or pos-
329 Renal Transplantation
sible clinical signs) of Creutzfeldt-Jacob disease.
Different circumstances apply when a recipient is already
infected with HIV or hepatitis and transplant from infectious
donors is possible in certain situations.
A previous history of malignancy need not be a contraindica-
tion for organ donation. However, absolute contraindications
are active cancer, or a history of metastatic cancer (with a
few exceptions, e.g. testicular cancer), and cancers with high
recurrence rates, e.g. lymphoma. Exclude metastasis as a
cause of intracranial bleeding in a potential donor with a brain
haemorrhage of unknown aetiology. For special exceptions in
malignancy, consult the full Guidelines.
Kidneys from marginal donors must have a calculated creati-
nine clearance rate (CrCl) of 50-60 mL/min. Kidneys with CrCl
< 50 mL/min are only suitable for dual transplant.
Recommendations for brain dead donors GR
Consider every brain-dead comatose subject as a
potential organ donor, without age limits.
Obtain agreement for organ harvesting from relatives
(significant others) according to local law and policies.
Authorisation for explantation by the donors close
relatives is always recommended, even if local legisla-
tion presumes consent.
Always exclude individuals who objected to donation
during life.
C
330 Renal Transplantation
A donor organ affected by a potentially transmissible
pathology (infections, neoplasias) must be carefully
evaluated considering the risk/benefits for the
recipient.
B
A good-quality organ must be guaranteed to the recipi-
ent and every transplant centre must establish its own
guidelines on organ acceptability. Marginal organs
can only be used after thorough assessment. Counsel
recipients and confirm their acceptance.
C
Surgical techniques GR
Living-donor transplantation is associated with higher
success rates than deceased-donor transplantation.
B
The surgeon is responsible for making sure the donor
is medically and psychologically suitable, the donated
organ is healthy, and success in the recipient is likely.
B
Always leave the donor with the better kidney. The
transperitoneal approach carries a higher risk of
splenic and intestinal complications.
B
Open-donor nephrectomy should be performed by an
extraperitoneal approach through a subcostal or dor-
sal lumbotomy incision.
B
Laparoscopic donor nephrectomy (either trans- or
retro-peritoneal) should only be performed by those
trained in the procedure.
B
Hand-assisted laparoscopic donor nephrectomy
minimises warm ischaemia time compared to classic
laparoscopic procedures.
B
Kidney recipient
Careful pre-operative work-up of all transplant candidates is
mandatory to improve organ and patient survival in the post-
transplant period. The work-up should be repeated regularly.
331 Renal Transplantation
Recommendations for pre-transplant therapy GR
In the abnormal urogenital tract, meticulous pre-trans-
plant work up is necessary, with urodynamics being
the key investigation.
B/C
If pharmacological therapy or intermittent catheterisa-
tion fails or is impossible, urinary diversion is necessary
using catheterisable pouches, conduits, or cystoplas-
ties.
B/C
Remove kidneys with autosomal-dominant polycystic
kidney disease if there is insufficient space or compli-
cations (chronically infected kidneys, or kidneys with
suspected tumour growth).
B/C
Other special considerations in a recipient
Recommendations GR
Active malignancy is a contraindication because
immunosuppression may aggravate underlying malig-
nancy jeopardising the patients life and graft outcome.
B
The waiting period before transplantation in recipients
with a history of malignancy depends on the type, TNM
stage and grade of the tumour, age, and general health.
B
Active infection may exacerbate after transplantation
and may be life-threatening.
B
Screen for viral and bacterial diseases in all transplant
candidates including hepatitis B (HBV), hepatitis C
(HCV), human immunodeficiency virus (HIV), cytome-
galovirus (CMV), and tuberculosis (TB).
332 Renal Transplantation
Routine screening examination of all patients in all
subspecialties is not necessary. However, a patient
with history and symptoms suspicious for an underly-
ing active infection should be seen by the appropriate
specialist (e.g. ear, nose, and throat specialist; dentist;
dermatologist; urologist and/or gynaecologist) to firmly
rule out infectious foci.
B
Re-evaluation of non-compliance (and serious morbi-
dity) may be appropriate.
C
The pre-transplant work-up should focus on looking
for cardiac disease. The work-up should be extensive
in patients at high risk of cardiac disease to firmly rule
out coronary artery disease. Perform any revascularisa-
tion before transplantation.
B
Peripheral artery disease is common in uraemic
patients. Special attention should be paid to iliacal,
peripheral, and cerebrovascular disease using appro-
priate diagnostic and therapeutic measures.
C
Patients with diabetes mellitus should be transplanted.
They require an extensive pre-transplant work-up.
B
Obesity itself is not a contraindication for transplanta-
tion. A thorough pre-transplant evaluation and attempt
to reduce weight are recommended.
C
Patients at risk of coagulopathies should be carefully
evaluated to prevent early post-transplant thrombotic
events.
C
Diseases that might influence post-transplant course
(e.g. diverticulosis, cholecystolithiasis, hyperparathy-
roidism) should be identified during pre-transplant
work-up and if possible treated before transplantation.
C
Age itself is not a contraindication, but the recipient
must undergo a thorough pre-transplant evaluation
and risk-benefit assessment and be counselled about
the increased risks associated with age.
B
333 Renal Transplantation
Recurrence of the original renal disease is common,
though graft loss due to recurrence is not. Only a few
rare diseases with a high recurrence rate leading to
early graft loss are contraindications for transplanta-
tion. Patients at risk of recurrent disease should be
counselled especially before living related-donor trans-
plantation.
C
Matching of donors and recipients
Recommendations GR
Determine ABO blood group and HLA-A, -B, and -DR
phenotypes of all candidates awaiting transplantation.
B
To avoid hyper-acute rejection (HAR), cross-matching
must be performed before transplantation.
B
Kidneys from deceased donors should be allocated to recipi-
ents with the lowest number of HLA mismatches. False-
positive results for cross-matching may occur especially in
autoimmune diseases. Potential recipients with a high per-
centage of panel-reactive antibodies (%PRA) can be further
analysed to ensure a negative cross-match. ABO blood group
matching prevents HAR, but technical advances have result-
ed in successful ABO-incompatible transplantation.
Immunosuppression after kidney transplantation
The current standard initial immunosuppression provides
excellent efficacy with good tolerability: calcineurin inhibitor
(CNI; cyclosporine or tacrolimus) + mycophenolate (myco-
phenolate mofetil [MMF] or enteric-coated mycophenolate
sodium [EC-MPS]) + corticosteroid (prednisolone or methyl-
prednisolone). Induction therapy may also be given.
334 Renal Transplantation
Recommendations for immunosuppressive therapy GR
Rejection prophylaxis using CNIs remains current best
practice.
A
Choice of CNI (cyclosporine or tacrolimus) depends on
immunological risk, recipient characteristics, concomi-
tant immunosuppression, and socio-economic factors.
A
Blood-level monitoring of both cyclosporine and
tacrolimus is mandatory to prevent under-immuno-
suppression (increased risk of rejection) and exces-
sively high blood levels (increased risk of chronic side-
effects, particularly nephrotoxicity).
A
Mycophenolates are the current standard of care. The
standard dose of MMF combined with cyclosporine is 1
g twice daily or EC-MPS 720 mg twice daily.
A
Combination therapy of Mycophenolates with
tacrolimus is not formally approved. Optimal myco-
phenolate (MPA) dosing is unclear, as tacrolimus-
treated patients have a higher MPA exposure than
cyclosporine-treated patients. The standard starting
dose of MMF combined with tacrolimus is MMF 1 g
twice daily or EC-MPS 720 mg twice daily. This dosage
is often dose-reduced with 30-50% lower doses at 1
year.
A
MPA monitoring cannot be recommended for all
patients due to limited evidence of benefit.
A
Azathioprine may be used in a low-risk population for
initial immunosuppression, especially in patients intol-
erant to MPA formulations.
A
Initial steroid therapy remains the standard of care in
perioperative and early postoperative period.
A
In order to reduce steroid associated side effects,
steroids may be stopped in most patients after 3-12
months on combination therapy with CNI and MPA.
A
335 Renal Transplantation
Recommendations for other immunosuppressive therapies
mTOR inhibitors (sirolimus, everolimus) GR
Acute rejection can be effectively prevented by inhibi-
tors of the mammalian target of rapamycin (mTOR)
(sirolimus, everolimus) combined with CNIs. Reduce
CNI dosage to avoid aggravated nephrotoxicity.
A
Initial CNI-free combination therapy of mTOR inhibi-
tors with MPA and steroids is not sufficient to prevent
acute rejection compared to a standard regimen.
A
Prophylactic surgical measures must be used when
mTOR inhibitors are given in the perioperative period
because of impaired wound healing.
A
mTOR inhibitors are an alternative to CNIs if there are
severe CNI-related side-effects.
A
Blood levels of sirolimus and everolimus must be regu-
larly monitored.
A
T-cell depleting induction therapy
Potential life-threatening side-effects include a higher
incidence of severe opportunistic infections and malig-
nancy, particularly post-transplant lymphoproliferative
disease.
B
T-cell depleting therapy has not resulted in improved
outcomes overall.
B
T-cell depleting therapy should not be routinely used in
a low-risk first-transplant recipient.
B
Patients must be informed of the increased risks of
infection and cancer.
B
Interleukin-2 receptor antibodies (IL-2R)
They reduce the rate of acute rejection, enabling CNI-
and steroid-sparing regimens.
A
Complications
Hyper-acute rejection (HAR) is rare and usually occurs within
336 Renal Transplantation
minutes or hours of vascularisation, although it may occur up
to 1 week post transplant. It is cured by graft removal.
Acute allograft rejection can be classified into acute cellular
rejection (ACR, T-cell mediated) or acute humoral rejection
(AHR, antibody-mediated). Test patients with ACR immediate-
ly for HLA IgG antibodies reactive with the graft. Steroid bolus
therapy is recommended as initial treatment. In severe, or
steroid-resistant, rejection, consider intensified immunosup-
pression, including high-dose steroid treatment, conversion
to tacrolimus, and T-cell depleting agents. Treatment of AHR
may include steroid bolus therapy, conversion to tacrolimus,
antibody elimination and intravenous immunoglobulin treat-
ment. Anti-CD20 (rituximab) or T-cell depleting agents may be
efficacious.
Chronic allograft dysfunction may take months or years to
develop. Perform a renal biopsy and determine donor-specific
alloantibodies if changes develop during follow-up monitor-
ing of serum creatinine, creatinine clearance, blood pressure,
blood lipids, and urinary protein excretion. If IF/TA is con-
firmed, begin appropriate medical treatment, e.g. control of
hypertension. Consider conversion to an mTOR inhibitor in
patients under current CNI therapy and/or with histological
signs suggesting CNI toxicity without significant proteinuria
(< 800 mg/day). Alternatives are substantial CNI reduction
under MPA protection or, in chronic maintenance patients,
CNI withdrawal under MPA and steroids.
Post-transplantation cancer is a common long-term cause of
death. Most malignancy affects the skin (40%) or lymphatic
system (11%). Closely monitor young recipients and patients
who have received T-cell depleting agents. Annual screening
for cancer and co-morbidity is mandatory.
337 Renal Transplantation
Annual screening
Lifelong regular post-transplant follow-up by an experienced
and trained transplant specialist is strongly recommended
at least every 6-12 months. Monitoring of renal function and
immunosuppression and side-effects by a physician, every 4-8
weeks is strongly advised.
This short booklet is based on the more comprehensive EAU guide-
lines (ISBN 978-90-79754-09-0), available to all members of the
European Association of Urology at their website,
http://www.uroweb.org.
338 Paediatric Urology
GUIDELINES ON
PAEDIATRIC UROLOGY
(Text update March 2013)
S. Tekgl (co-chair), H. Riedmiller (co-chair), H.S. Dogan,
P. Hoebeke, R. Kocvara, J.M. Nijman (vice-chair),
Chr. Radmayr, R. Stein
Introduction
Due to the scope of the extended Guidelines on Paediatric
Urology, no attempt has been made to include all topics, but
rather to provide a selection based on practical considera-
tions.
PHIMOSIS
Background
At the end of the first year of life, retraction of the foreskin
behind the glanular sulcus is possible in only about 50% of
boys. The phimosis is either primary (physiological), with no
sign of scarring, or secondary (pathological), resulting from
scarring due to conditions such as balanitis xerotica obliter-
ans.
Phimosis must be distinguished from normal agglutination
of the foreskin to the glans, which is a physiological phenom-
enon. If the tip remains narrow and glanular adhesions are
separated, then the space is filled with urine during voiding,
causing the foreskin to balloon outward.
339 Paediatric Urology
Treatment
Plastic circumcision (dorsal incision, partial circumcision) car-
ries the potential for recurrence of the phimosis. Associated
frenulum breve is corrected by frenulotomy. Meatoplasty is
added if necessary. Childhood circumcision should not be rec-
ommended without a medical reason.
Circumcision: indication and contraindication
Contraindications for circumcision are coagulopathy, an
acute local infection and congenital anomalies of the penis,
particularly hypospadias or buried penis, because the foreskin
may be required for a reconstructive procedure.
Conservative treatment
Agglutination of the foreskin does not respond to steroid
treatment.
Paraphimosis
It is characterised by retracted foreskin with the constrictive
ring localised at the level of the sulcus. A dorsal incision of the
constrictive ring may be required, or circumcision is carried
out immediately or in a second session.
CRYPTORCHIDISM
Clinical management is determined by classification into pal-
pable and non-palpable testes.
Diagnosis
Physical examination is the only method of differentiating
palpable and non-palpable testes. There is no benefit from
ultrasonography (US), computed tomography (CT), magnetic
resonance imaging (MRI) or CT angiography (CTA).
Surgical treatment
Surgery differs for palpable or non-palpable testes.
340 Paediatric Urology
Orchidopexy (inguinal approach) is used for palpable testis
(up to 92% success). Inguinal surgical exploration should be
attempted for non-palpable testes. Laparoscopy can be used
for testis removal or orchidolysis and orchiopexy.
Prognosis
Boys with one undescended testis have a lower fertility rate,
but the same paternity rate as boys with bilateral descended
testes. Boys with an undescended testis are 20 times more
likely to develop testicular malignancy, independent of treat-
ment choice.
Recommendations for cryptorchidism LE GR
Boys with retractile testes do not need medical
or surgical treatment, but require close follow-
up until puberty.
2 A
Surgical orchidolysis and orchidopexy should
be concluded at the age of 12 months, or 18
months the latest.
3 B
In case of non-palpable testes and no evidence
of disorders of sex development, laparoscopy
still represents the gold standard because it
has almost 100% sensitivity and specificity in
identifying an intraabdominal testis as well as
the possibility for subsequent treatment in the
same session.
1b A
Hormonal therapy, either in an adjuvant or neo-
adjuvant setting, is not standard treatment.
Patients have to be evaluated on an individual
basis.
2 C
For an intra-abdominal testis in a 10-year-old
boy or older, with a normal contralateral testis,
removal is an option because of the theoretical
risk of a later malignancy.
3 B
341 Paediatric Urology
HYDROCELE
Background
Incomplete obliteration of the processus vaginalis peritonei
results in formation of various types of communicating
hydrocele, alone or connected with other intrascrotal
pathology (hernia).
Non-communicating hydroceles are found secondary to minor
trauma, testicular torsion, epididymitis, or varicocele opera-
tion, or may appear as a recurrence after primary repair of a
communicating hydrocele.
A communicating hydrocele vacillates in size, usually relative
to activity. It is diagnosed by medical history and physical
investigation, the swelling is translucent, and transillumina-
tion of the scrotum makes the diagnosis. If there are any
doubts about the intrascrotal mass, US should be performed.
Contralateral disease should be excluded.
Surgical treatment
Surgical treatment of hydrocele is not indicated within the
first 12-24 months because of the tendency for spontaneous
resolution.
Early surgery is indicated if there is suspicion of a concomi-
tant inguinal hernia or underlying testicular pathology.
There is no evidence that this type of hydrocele risks
testicular damage.
In the paediatric age group, the operation consists of ligation
of the patent processus vaginalis via an inguinal incision, leav-
ing the distal stump open, whereas in hydrocele of the cord,
the cystic mass is excised or unroofed. Sclerosing agents
should not be used because of the risk of chemical peritonitis
in the communicating processus vaginalis peritonei.
342 Paediatric Urology
The scrotal approach (Lord or Jaboulay technique) is used in
the treatment of a secondary non-communicating hydrocele.
HYPOSPADIAS
Background
Hypospadias are usually classified according to the anatomi-
cal location of the proximally displaced urethral orifice:
distal - anterior hypospadias (glanular, coronal or distal
penile);
intermediate - middle (penile);
proximal - posterior (penoscrotal, scrotal, perineal).
The pathology may be much more severe after skin release.
Assessment
Patients with hypospadias should be diagnosed at birth. The
diagnostic evaluation also includes an assessment of associ-
ated anomalies, which are cryptorchidism and open proces-
sus vaginalis or inguinal hernia. Severe hypospadias with
unilaterally or bilaterally impalpable testis, or with ambiguous
genitalia, require a complete genetic and endocrine work-up
immediately after birth to exclude intersexuality, especially
congenital adrenal hyperplasia.
Trickling urine and ballooning of the urethra require exclusion
of meatal stenosis.
The length of the hypospadiac penis may be distorted by
penile curvature, by penoscrotal transposition, or may be
smaller due to hypogonadism.
Differentiation between functionally necessary and aestheti-
cally feasible operative procedures is important for therapeu-
tic decision-making. As all surgical procedures carry the risk
of complications, thorough pre-operative counselling of the
parents is crucial. The therapeutic objectives are to correct
343 Paediatric Urology
the penile curvature, to form a neo-urethra of an adequate
size, to bring the neomeatus to the tip of the glans, if possible,
and to achieve an overall acceptable cosmetic appearance.
This goal is achieved by using different surgical techniques
according to the individual findings.
Surgery
For repeat hypospadias repairs, no definitive guidelines can
be given.
Outcome
Excellent long-term functional and cosmetic results can be
achieved after repair of anterior penile hypospadias. The com-
plication rate in proximal hypospadias repair is higher.
Fig. 1 gives an algorithm for the management of hypospadias.
344 Paediatric Urology
Fig. 1: Algorithm for the management of hypospadias
D.S.D. = disorders of sexual differentiation; GAP = glans
approximation procedure; TIP = tubularized incised plate ure-
throplasty; MAGPI = meatal advancement and glanuloplasty
incorporated.
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345 Paediatric Urology
MICROPENIS
Micropenis is defined as a small but otherwise normally
formed penis with a stretched length of less than 2.5 cm SD
below the mean (Table 1).
Table 1: Length of the penis in boys
(according to Feldmann and Smith)
Age Mean SD (cm)
Newborns 3.5 0.4
0-5 months 3.9 0.8
6-12 months 4.3 0.8
1-2 y 4.7 0.8
2-3 y 5.1 0.9
3-4 y 5.5 0.9
4-5 y 5.7 0.9
5-6 y 6.0 0.9
6-7 y 6.1 0.9
7-8 y 6.2 1.0
8-9 y 6.3 1.0
9-10 y 6.3 1.0
10-11 y 6.4 1.1
Adults 13.3 1.6
VARICOCELE IN CHILDREN AND ADOLESCENTS
Background
Varicocele is unusual in boys under 10 years of age, but
becomes more frequent at the beginning of puberty. Fertility
problems will arise in about 20% of adolescents with vari-
cocele. The adverse influence of varicocele increases with
time.
Testicular catch-up growth and improvement in sperm para-
346 Paediatric Urology
meters after varicocelectomy has been reported in adoles-
cents.
Varicocele is mostly asymptomatic, rarely causing pain at this
age. It may be noticed by the patient or parents, or discovered
by the paediatrician at a routine visit. Diagnosis and clas-
sification depends upon the clinical finding and ultrasound
investigation.
Surgical treatment
Surgical intervention is based on ligation or occlusion of the
internal spermatic veins. Microsurgical lymphatic-sparing
repair (microscopic or laparoscopic) are associated with the
lowest recurrence and complication rates. There is no evi-
dence that treatment of varicocele at paediatric age will offer
a better andrological outcome than an operation performed
later.
Follow-up
During adolescence, testicular size should be checked annu-
ally. After adolescence, repeated sperm analysis is to be rec-
ommended.
Fig. 2 shows an algorithm for the diagnosis of varicocele in
children and adolescents, and Fig. 3 shows an algorithm for its
treatment.
347 Paediatric Urology
Fig. 2: Algorithm for the diagnosis of varicocele in children and ado-
lescents
Fig. 3: Algorithm for the treatment of varicocele in children and ado-
lescents
Varicocele in children
and adolescents
Physical examination
in the upright position
Ultrasound
investigation
Grade I - Valsalva positive
Grade II - Palpable
Grade III - Visible
Size of the testes
Venous reux detected on
Doppler US
Varicocele in children
and adolescents
Small testis (growth arrest)
Additional testicular
pathology
Bilateral palpable
varicocele
Pathological spermiogram
Symptomatic varicocele
Microsurgical lymphatic-
sparing repair (microscopic
or laparoscopic)
Measurement of testicular
size (during adolescence)
Repeated sperm analysis
(afer adolescence)
Symmetrical testes


Normal spermiogram
(in older adolescents)
Surgery:
Indication
Type
Conservative treatment:
Indication
Follow-up
348 Paediatric Urology
MONOSYMPTOMATIC NOCTURNAL ENURESIS
Background
Enuresis is incontinence during the night. Any wetting during
sleep above the age of five years is enuresis. It is important
to note that there is a single symptom only. Due to an imbal-
ance between night-time urine output and night-time bladder
capacity, the bladder can easily become full at night, and the
child will either wake up to empty the bladder or will void dur-
ing sleep.
Assessment
A voiding diary, registering the daytime bladder function and
the night-time urine output will help guide the treatment.
Measuring the daytime bladder capacity gives an estimate of
bladder capacity to compare with normal values for age.
Fig. 4 gives an algorithm for the diagnosis and treatment of
monosymptomatic nocturnal enuresis.
349 Paediatric Urology
Fig. 4: Algorithm for the diagnosis and treatment of monosympto-
matic nocturnal enuresis
Vesicouretereric Reflux (VUR) in children
VUR present within a wide range of severity, and a majority of
reflux patients will not develop renal scars and probably will
not need any intervention. The main goal in management is
the preservation of kidney function.
Diagnosis
The diagnostic work-up should evaluate the overall health and
development of the child. A basic diagnostic work-up includes
a detailed medical history (including family history, and
screening for lower urinary tract dysfunction [LUTD]), physical
examination including blood pressure measurement, urinaly-
Nocturnal enuresis
Education
Supportive therapy
Alarm or desmopressin
Initial assessment
Voiding diary or
direct questioning
Voiding habits
Weting episodes
Bowel function
Urinalysis
Daytime weting
Urge syndrome
Lower tract dysfunction
Infection
Other
Uroowmetry, urine V, Osm *
Urotherapy, Ab, Ach, **
Biofeedback
Check for night time polyuria
investigate for sleep disorders
Overactivity of the bladder
Consider longer use of desmopression
Combination therapies
Imipramine
Monosymptomatic
Nocturnal enuresis
still wet
350 Paediatric Urology
sis (assessing proteinuria), urine culture, and serum creatinine
in patients with bilateral renal parenchymal abnormalities.
Prenatally diagnosed hydronephrosis
Ultrasound of the kidney and bladder is the first stand-
ard evaluation tool for children with prenatally diagnosed
hydronephrosis. It should be delayed to the end of first week
after birth because of early oliguria in the neonate. It is essen-
tial to evaluate the bladder, as well as the kidneys.

Recommendations for the use of VCU in prenatal hydrone-
phrosis
US findings of bilateral high-grade hydronephrosis, duplex
kidneys, ureterocele, ureteric dilatation, and abnormal blad-
ders, because the likelihood of VUR is much higher.
In all other conditions, the use of VCU to detect reflux is
optional.
When cases identified by prenatal US become symptomatic
with UTIs, further evaluation with VCU should be consid-
ered.
Recommendations for paediatric screening of VUR
The parents of children with VUR should be informed that
siblings and offspring have a high prevalence of VUR.
If screening is performed, siblings should be screened by
renal US. VCU is recommended if there is evidence of renal
scarring on US or a history of UTI.
In older children who are toilet-trained, there is no added
value in screening for VUR.
UTI = urinary tract infecting; VCU = voiding cystourethro-
graphy.
351 Paediatric Urology
Conservative therapy
The objective of conservative therapy is prevention of febrile
UTI. It is based on the understanding that:
VUR resolves spontaneously, mostly in young patients with
low-grade reflux. However, spontaneous resolution is low
for bilateral high-grade reflux).
VUR does not damage the kidney when patients are free of
infection and have normal lower urinary tract function.
There is no evidence that small scars can cause hyperten-
sion, renal insufficiency or problems during pregnancy.
The conservative approach includes watchful waiting,
intermittent or continuous antibiotic prophylaxis, and blad-
der rehabilitation in those with LUTD.
Circumcision during early infancy may be considered as
part of the conservative approach, because it is effective
in reducing the risk of infection in normal children.
Surgical treatment
Surgical treatment comprises endoscopic injection of bulking
agents or ureteral reimplantation.
Subureteric infection of bulking agents: due to the availability
of biodegradable substances, endoscopic subureteric injec-
tion of bulking agents has become an alternative to long-term
antibiotic prophylaxis and surgical intervention.
Open surgical techniques: Overall, all surgical procedures
offer very high and similar success rates for correcting VUR.
Laparoscopy: a laparoscopic approach cannot be recom-
mended as a routine procedure. It can be offered as an
alternative to the parents in centres where there is enough
experience.
352 Paediatric Urology
Recommendations for the management of VUR in
childhood
Regardless of the grade of reflux or presence of renal scars,
all patients diagnosed within the first year of life should be
treated initially with CAP. During early childhood, the kid-
neys are at higher risk of developing new scars. Immediate,
parenteral antibiotic treatment should be initiated for febrile
breakthrough infections. Definitive surgical or endoscopic
correction is the preferred treatment in patients with fre-
quent breakthrough infections.
Surgical correction should be considered in patients with
persistent high-grade reflux (grades IV/V). There is no con-
sensus about the timing and type of surgical correction.
The outcome of open surgical correction is better than
endoscopic correction for higher grades of reflux, whereas
satisfactory results can be achieved by endoscopic injection
for lower grades.
There is no evidence that correction of persistent low-grade
reflux (grades IIII) without symptoms and normal kidneys
offers a significant benefit. These patients may be candi-
dates for endoscopic treatment.
In all children presenting at age 15 years, CAP is the pre-
ferred option for initial therapy. For those with high-grade
reflux or abnormal renal parenchyma, surgical repair is a rea-
sonable alternative. In patients with lower grades of reflux
and without symptoms, close surveillance without antibiotic
prophylaxis may be an option.
A detailed investigation for the presence of LUTD should
be performed in all children after toilet-training. If LUTD is
found, the initial treatment should always be for LUTD.
If parents prefer definitive therapy to conservative manage-
ment, surgical correction may be considered. Endoscopic
treatment is an option for all children with low grades of
reflux.
353 Paediatric Urology
The traditional approach of initial medical treatment after
diagnosis and shifting to interventional treatment in case of
breakthrough infections and new scar formation needs to
be challenged, because the treatment should be tailored to
different risk groups.
The choice of management depends on the presence of
renal scars, clinical course, grade of reflux, ipsilateral renal
function, bilaterality, bladder function, associated anomalies
of the urinary tract, age, compliance, and parental prefer-
ence. Febrile UTI, high-grade reflux, bilaterality, and cortical
abnormalities are considered to be risk factors for possible
renal damage. The presence of LUTD is an additional risk
factor for new scars.
In high-risk patients who already have renal impairment, a
more aggressive, multidisciplinary approach is needed.
CAP = continuous antibiotic prophylaxis.
354 Paediatric Urology
Risk
Groups
Presentation Initial treatment Follow-up
High Symptomatic male
or female patients
after toilet-training
with high-grade reflux
(grades IV/V), abnormal
kidneys and LUTD
Initial treatment is
always for LUTD; inter-
vention may be consid-
ered in cases of recur-
rent febrile infections
or persistent reflux
Greater possibility of earlier
intervention
More aggressive follow-up
for UTI and LUTD; full re-
evaluation after 6 months
High Symptomatic male
or female patients
after toilet-training
with high-grade reflux
(grade IV/V), abnormal
kidneys and no LUTD
Intervention should be
considered
Open surgery has better results
than endoscopic surgery
Postoperative VCU on
indication only; follow-up
of kidney status until after
puberty
Moderate Symptomatic male or
female patients before
toilet-training, with
high-grade reflux and
abnormal kidneys
CAP is the initial treat-
ment. Intervention
may be considered in
cases of breakthrough
infections or persistent
reflux
Spontaneous resolution is
higher in males
Follow-up for UTI/hydro-
nephrosis; full re-evalua-
tion after 1224 months
Moderate Asymptomatic patients
(PNH or sibling) with
high-grade reflux and
abnormal kidneys
CAP is the initial treat-
ment. Intervention
may be considered in
cases of breakthrough
infections or persistent
reflux
Follow-up for UTI/hydro-
nephrosis; full re-evalua-
tion after 1224 months
Table 2: Management and follow-up according to
different risk groups
355 Paediatric Urology
Risk
Groups
Presentation Initial treatment Follow-up
High Symptomatic male
or female patients
after toilet-training
with high-grade reflux
(grades IV/V), abnormal
kidneys and LUTD
Initial treatment is
always for LUTD; inter-
vention may be consid-
ered in cases of recur-
rent febrile infections
or persistent reflux
Greater possibility of earlier
intervention
More aggressive follow-up
for UTI and LUTD; full re-
evaluation after 6 months
High Symptomatic male
or female patients
after toilet-training
with high-grade reflux
(grade IV/V), abnormal
kidneys and no LUTD
Intervention should be
considered
Open surgery has better results
than endoscopic surgery
Postoperative VCU on
indication only; follow-up
of kidney status until after
puberty
Moderate Symptomatic male or
female patients before
toilet-training, with
high-grade reflux and
abnormal kidneys
CAP is the initial treat-
ment. Intervention
may be considered in
cases of breakthrough
infections or persistent
reflux
Spontaneous resolution is
higher in males
Follow-up for UTI/hydro-
nephrosis; full re-evalua-
tion after 1224 months
Moderate Asymptomatic patients
(PNH or sibling) with
high-grade reflux and
abnormal kidneys
CAP is the initial treat-
ment. Intervention
may be considered in
cases of breakthrough
infections or persistent
reflux
Follow-up for UTI/hydro-
nephrosis; full re-evalua-
tion after 1224 months
356 Paediatric Urology
Moderate Symptomatic male or
female patients after
toilet-training, with
high-grade reflux and
normal kidneys with
LUTD
Initial treatment is
always for LUTD.
Intervention may be
considered in cases of
breakthrough infec-
tions or persistent
reflux
In case of persistent LUTD,
despite urotherapy, interven-
tion should be considered. The
choice of intervention is con-
troversial
Follow-up for UTI and
LUTD, kidney status; full
re-evaluation after suc-
cessful urotherapy
Moderate Symptomatic male or
female patients after
toilet-training with low-
grade reflux, abnormal
kidneys with or without
LUTD
Choice of treatment
is controversial.
Endoscopic treatment
may be an option.
LUTD treatment should
be given if needed.
Follow-up for UTI, LUTD,
and kidney status until
after puberty
Moderate All symptomatic
patients with normal
kidneys, with low-grade
reflux, with LUTD
Initial treatment is
always for LUTD
Follow-up for UTI and
LUTD
Low All symptomatic
patients with normal
kidneys, with low-grade
reflux, with no LUTD
No treatment or CAP If no treatment is given, parents
should be informed about risk
of infection
Follow-up for UTI
Low All asymptomatic
patients with normal
kidneys with low-grade
reflux
No treatment or CAP in
infants
If no treatment is given, parents
should be informed about risk
of infection
Follow-up for UTI
PNH = prenatal diagnosed hydronephrosis.
357 Paediatric Urology
Moderate Symptomatic male or
female patients after
toilet-training, with
high-grade reflux and
normal kidneys with
LUTD
Initial treatment is
always for LUTD.
Intervention may be
considered in cases of
breakthrough infec-
tions or persistent
reflux
In case of persistent LUTD,
despite urotherapy, interven-
tion should be considered. The
choice of intervention is con-
troversial
Follow-up for UTI and
LUTD, kidney status; full
re-evaluation after suc-
cessful urotherapy
Moderate Symptomatic male or
female patients after
toilet-training with low-
grade reflux, abnormal
kidneys with or without
LUTD
Choice of treatment
is controversial.
Endoscopic treatment
may be an option.
LUTD treatment should
be given if needed.
Follow-up for UTI, LUTD,
and kidney status until
after puberty
Moderate All symptomatic
patients with normal
kidneys, with low-grade
reflux, with LUTD
Initial treatment is
always for LUTD
Follow-up for UTI and
LUTD
Low All symptomatic
patients with normal
kidneys, with low-grade
reflux, with no LUTD
No treatment or CAP If no treatment is given, parents
should be informed about risk
of infection
Follow-up for UTI
Low All asymptomatic
patients with normal
kidneys with low-grade
reflux
No treatment or CAP in
infants
If no treatment is given, parents
should be informed about risk
of infection
Follow-up for UTI
This short text is based on the more comprehensive EAU/ESPU
Paediatric Urology Guidelines (ISBN 978-90-79754-71-7), available at
their website, http://www.uroweb.org.