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Update on Prostatitis and

Treatments

BAUN Benign Study Day


14/03/2012
Mr Richard Cetti
Specialist Registrar Urology, QA Portsmouth
Prostatitis an Important Problem!

 Prevalence 2.2-13.8%
 Quality of life

 Economic Costs
Prostatitis an Important Problem!

 ‘Pain management is a necessity in the work of


each physician.’
F. Sauerbruch, 1936
Introduction
 Pain
 Classification/Terminology
 Presentation
 Investigation
 Treatment- historical, contemporary and the
evidence
 The Future
Pain
-an unpleasant sensory and emotional experience

Hypogastric Nerve
Pelvic Nerves
Pudendal Nerve

Brain Ascending Syst Dorsal Horn Periphery


Convergence
Projection
Theory (Ruch)
Skin

Viscus
Chronic Pain
 Combination of:
- Neuroplasticity
- Central processing altered
- Trophic changes in subcutaneous tissue and muscle
 All site normal sensations become painful (allodynia).
 At site painful stimuli become more painful
(hyperalgesia).
 Zone affected adjacent tissue (secondary hyperalgesia).
Aetiology of Chronic Prostatitis
 Poorly understood
 Multiple factors within and between patients
 Hypotheses:
- Presence of antibiotic resistant non-culturable micro-organisms
- Chemical irritation
- Intra-ductal reflux and obstruction
- Dysfunctional high pressure voiding
- Neuropathic pain
- Pudendal nerve entrapment
- Autoimmune
Classification
Classification- NIH/EAU
 Cat I Acute bacterial prostatitis
 Cat II Chronic bacterial prostatitis
 Cat III Prostate Pain Syndrome (CPPS)
 Cat IV Asymptomatic inflammatory prostatitis
Classification- NIH/EAU
 Cat I Acute bacterial prostatitis
 Cat II Chronic bacterial prostatitis
 Cat III Prostate Pain Syndrome (CPPS)
Discomfort or pain in the pelvic region for at least 3
months with variable voiding and sexual symptoms, no
demonstrable infection.
IIIa- inflammatory PPS- white cells in semen/eps/post
eps urine
IIIb- non-inflammatory
 Cat IV
Evaluation
 3 main factors:

 Symptoms
 WBC’s

 Bacteria
Evaluation
 History
 Focused Examination
 Condition Specific Questionnaires
 Urinalysis and Culture
 Semen culture
 Optional: PSA, Urinary Cytology, US,
Cystoscopy, Urodynamics, Psychosocial
evaluation
Evaluation
 History
 Focused Examination
 Condition Specific Questionnaires
 Urinalysis and Culture
 Semen culture
 Optional: PSA, Urinary Cytology, US,
Cystoscopy, Urodynamics, Psychosocial
evaluation
Evaluation
 History
 Focused Examination
 Condition Specific Questionnaires
 Urinalysis and Culture
 Semen culture
 Optional: PSA, Urinary Cytology, US,
Cystoscopy, Urodynamics, Psychosocial
evaluation
Evaluation
 History
 Focused Examination
 Condition Specific Questionnaires
 Urinalysis and Culture
 Semen culture
 Optional: PSA, Urinary Cytology, US,
Cystoscopy, Urodynamics, Psychosocial
evaluation
Evaluation
IPSS Chronic Prostatitis Symptom Index
Evaluation
 History
 Focused Examination
 Condition Specific Questionnaires
 Urinalysis and Culture
 Semen culture
 Optional: PSA, Urinary Cytology, US,
Cystoscopy, Urodynamics, Psychosocial
evaluation
Evaluation
 Meares-Stamey ‘4 Glass
Test’
- 1st 10-15ml of voided
urine VB1
- MSU 10-15ml urine VB2
- Prostate Massage- EPS
- 1st 10-15ml voided urine
post massage VB3
- Modified: VB1 and VB3
Evaluation
 History
 Focused Examination
 Condition Specific Questionnaires
 Urinalysis and Culture
 Semen culture
 Optional: PSA, Urinary Cytology, US,
Cystoscopy, Urodynamics, Psychosocial
evaluation
Evaluation
 History
 Focused Examination
 Condition Specific Questionnaires
 Urinalysis and Culture
 Semen culture
 Optional: PSA, Urinary Cytology, US,
Cystoscopy, Urodynamics, Psychosocial
evaluation
Evaluation

‘Diagnosis of exclusion’
Treatment- Organcentric vs.
Snowflake
Traditional Organcentric Model
 Pathogenesis simple
Traditional Organcentric Model
 Pathogenesis simple
Infection
‘itis’

Inflammation

PAIN!
Traditional Organcentric Model
 Pathogenesis simple  Antibiotics
Infection  Anti-inflammatories
‘itis’  Alpha blockers
 Treatment simple?
Inflammation

PAIN!
Antibiotics
 Ciprofloxacin, ofloxacin, levofloxacin
 ~10% patients will have culturable bacteria.
 J Urol. 2001 May;165(5):1539-44. Predictors of patient response to
antibiotic therapy for the chronic prostatitis/chronic pelvic pain
syndrome: a prospective multicenter clinical trial. Nickel JC et al.
 However, 57% of patients on ofloxacin saw improvement
 Trial 2 weeks and continue for 6 if benefit.
Alpha-blockers
 Alfuzosin, Terazosin, Tamsulosin
 N Engl J Med. 2008 Dec 18;359(25):2663-73. Alfuzosin and
symptoms of chronic prostatitis-chronic pelvic pain syndrome Nickel
JC et al.
 Multicenter, randomized, double-blind, placebo-controlled trial of
alfuzosin.
 272 men were randomly assigned to treatment for 12 weeks with
either 10 mg of alfuzosin/day or placebo.
 The primary outcome was a reduction of at least 4 points in the
CPSI score.

Placebo Alfuzosin
N=134 N=138
CPSI responders 66(49%) 68(49%)
Anti-inflammatories
 Celecoxib, rofecoxib
 J Urol. 2003 Apr;169(4):1401-5. A randomized, placebo controlled,
multicenter study to evaluate the safety and efficacy of rofecoxib in
the treatment of chronic nonbacterial prostatitis. Nickel JC et al.
 Multicenter, randomized, double-blind, placebo-controlled trial of
rofecoxib.
 161 men were randomly assigned to treatment with either 25-50 mg
of rofecoxib/day or placebo.
 Of the patients, 79% on 50 mg rofecoxib versus 59% on placebo
reported no or mild pain. But not statistically significant.
Neuropathic Painkillers
 Amitriptylline, Pregabalin
 Arch Intern Med. 2010 Sep 27;170(17):1586-93. Pregabalin for the
treatment of men with chronic prostatitis/chronic pelvic pain
syndrome: a randomized controlled trial. Pontari MA et al.
 Multicenter, randomized, double-blind, placebo-controlled trial of
pregabalin.
 218 men were randomly assigned to treatment for 6 weeks with
either 150-600 mg of pregabalin/day or placebo.
 The primary outcome was a reduction of at least 6 points in the
CPSI score.

Placebo Pregabalin
N=106 N=218
CPSI Responders 38(36%) 103(47.2%)
So are we getting desperate?

 Laparoscopic prostatectomy for chronic


prostatitis

This study is currently recruiting participants.


Verified by the Krongrad Institute Oct 2008.
ClinicalTrials.gov identifier: NCT00775515
UPOINT
Urinary

Tenderness Psychosocial

Neurogenic/Systemic Organcentric

Infection
UPOINT
 Retrospective study of 90 CPPS patients seen by
one Urologist over 12 months

Domain Percentage
Urinary 52
Psychosocial 34
Organ Specific 61
Infection 16
Neurogenic/Systemic 37
Tenderness 53
The Future: Patient-centric treatment.
‘Phenotyping’
Novel Therapies
 Cernilton
 Eur Urol. 2009 Sep;56(3):544-51. A pollen extract (Cernilton) in
patients with inflammatory chronic prostatitis-chronic pelvic pain
syndrome: a multicentre, randomised, prospective, double-blind,
placebo-controlled phase 3 study. Wagenlehner FM et al.
 Multicentre, prospective, randomised, double-blind, placebo-
controlled trial in men with CP/CPPS (NIH IIIA)
 Primary end-point, defined as a decrease of the CPSI total score by
at least 25% or at least 6 points.

Placebo Cernilton
N=69 N=70
CPSI Responders 50% 71%
Take Home Points
 Poorly understood aetiology/pathogenesis.
 Heterogenous disease.
 Established treatments perform poorly in RCT’s.
 Phenotyping patient and treatment.

 ‘Active exclusion, Active Inclusion’


‘Active exclusion, Active Inclusion’
‘Active exclusion, Active Inclusion’