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Cervical Cancer

The Society of Gynecologic Oncologist of the Philippines

(Foundation), Inc.
Unit 414 Manila Astral Tower
1330 Taft Avenue corner P. Faura Street
Ermita Manila
Telefax No: 526-47-87

Officers 2008-2010
Immediate Past President
Board of Directors

Rey H. Delos Reyes, MD, MHSA

Gil S. Gonzalez, MD
Ma. Cynthia F. Tan, MD
Ma. Lilibeth L. Sia Su, MD
Mary Christine F. Palma, MD
Efren J. Domingo,MD, PhD
Teresita B. Cardenas, MD
Benjamin D. Cuenca, MD
Aris Luke I. Dungo, MD
Cecilia L. Llave, MD, PHD
Jericho Thaddeus P. Luna, MD
Manuel S. Manabat, MD,
Concepcion D. Rayel, MD
Rafael S. Tomacruz, MD

Philippine Board of Gynecologic Oncology


Gil S. Gonzalez, MD
Cecilia L. Llave, MD, PhD
Virgilio R. Oblepias, MD l Sign up and open your clinic to the world.


II. Malignant Disease

Cervical Cancer
1. Cervical cancer is diagnosed by biopsy1(Benedet 2006).
2. Cervical cancer is staged clinically (Appendix C.I)1
3. If clinically indicated, proctosigmoidoscopy and cystoscopy should be done to rule out invasion. Metastatic
work-ups include renal imaging studies (IVP), liver
function tests, chest x-ray, and skeletal survey1.
4. Special diagnostic imaging studies may be done to
guide treatment planning: ultrasound, magnetic resonance imaging (MRI), computed tomography scan (CT
scan), positron emission tomography scan (PET scan),
PET CT Scan and bone scintigraphy1. These imaging
studies will not be part of the staging
a. MRI is more accurate than CT scan in determining
the following2
i. Primary tumor volume
ii. Vaginal invasion
iii. Parametrial involvement
iv. Bladder and rectal involvement
b. PET CT scan is more accurate in determining
lymph node involvement3
c. KUB IVP and barium enema not routinely indicated
anymore as MRI and CT scan are more accurate2
d. Cystoscopy and protosigmoidoscopy should be
reserved for women in whom a normal bladder or
rectum cannot be confirmed on clinical or radiological assessment2
5. Concurrent chemotherapy and complete radiotherapy
(chemoradiation) is the standard of treatment.4-9
6. For patients who are unable to receive chemotherapy,
radiation treatment alone may be given10.
7. Adenocarcinomas have shown no significant difference in clinical behavior from squamous cell carcinomas9,10.
I. Biopsy Proven Premalignant Lesions11(ASCCP 2006 Guidelines)

Cervical Cancer




1. Preceded by
Diagnostic Excisional

ASCUS, ASC-H, Procedures:
LSIL: Follow up
every 6-12 months [Level 3a]
11,12(ALTS Follow up study 2003)
[Level 2b]

2. Preceded by HSIL,
AGC: Follow up
every 6 months
OR Diagnostic exci sional Procedure11,12
[Level 3b]

CIN 2,3 1. Cryotherapy11
[Level 1a]

2. Conization: Cold-
Knife Cone Biopsy
or LEEP/LLETZ11,13,14
[Level 1a]

Diagnostic Excisional
(Massad 2001/Dunn 2003)

[Level 2a]


1. Desirous of pregnancy,
no lymphovascular space
a. Negative margins
observe1,15-19 (Benedetti Panici

2007 review)
[Level 1b]
b. Positive margins - repeat
cone biopsy1,15-19
[Level 1b]
Stage 0a Good
2. Not desirous of pregnancy
Stage I A 1a surgical a. Extrafascial hyste
risk rectomy (EH) with
or without bilateral sal-
pingo- oophorectomy
( BSO)1,15-19
[Level 1b]
b. Vaginal extrafascial
hysterectomy ( BSO)15
[Level 1b]
c. If positive for lympho vascular space invasion

(LVSI): modified radical
hysterectomy( BSO)
with bilateral pelvic
lymph node dissection
1,15,21(Benedetti Panici 2007 Review,

Koliopoulous 2007 review


1. Negative margins observe1,15-19 (Benedetti Panici

2007 review)
[Level 1b]

2. Positive margins
Poor a. Repeat Cone/LEEP 1,15-19

surgical (Benedetti Panici 2007 review)

risk b. Intracavitary Radio therapy (Brachytherapy):
High Dose Rate (HDR)
or Low Dose Rate (LDR)
3. Positive LVSI pelvic
EBRT + brachytherapy
[Level 3c]

1. Desirous of pregnancy,
Radical trachelectomyc
and extra-peritoneal or
Laparoscopic pelvic

[Level 2b]

2. Not desirous of pregnancy

Modified radical hyste rectomy (MRH), bilateral
pelvic lymph node dis section (BLND) BSO16,24
[Level 1b]
Stage IA2

Pelvic External Beam

Poor Radiotherapy (EBRT)b

surgical + Brachytherapy

risk [Complete RT] 21 (Koliopoulous 2007)
[Level2b] l Sign up and open your clinic to the world.


Cervical Cancer
a. Stages 0, IA1 and IA2 are diagnosed by cone biopsy
(cold-knife or LEEP/LLETZ).1
b. Pelvic EBRT includes the upper half of the vagina.
c. Radical vaginal trachelectomy and laparoscopic
extraperitoneal pelvic lymphadenectomy23 inclusion
1. Desire to preserve fertility
2. No clinical evidence of impaired fertility
3. FIGO Stage 1a2-1B1
4. Lesion size less than 2 cms
5. No evidence of pelvic lymph node metastasis
6. No LVSI
7. Informed consent

1. Radical hysterectomy
(RH), BLND Para aortic lymph node
sampling BSO25-26
[Level 1a]

2. Concurrent chemotherapya
and pelvic EBRT + Brachy
Stage therapy (Chemoradia IB1 , IIA Good tion)27,28 [Level 1a]
(tumor surgical
3. Radical Vaginal Hyste diameter risk rectomy BSO and extra
<4 cms.) peritoneal or laparoscopy
assisted pelvic lympha denectomyb 29,30[Level IC]

4. Radical trachelectomyc
and extra-peritoneal or
Laparoscopic pelvic
[Level 2b]




Concurrent chemotherapya
and pelvic EBRT +
[Level 1a]

a. Standard Chemotherapy drug to use for concurrent treatment with radiotherapy:
Cisplatin 40 mg/ m2 given weekly for 6 courses during
pelvic EBRT1,4-9 [Level 1a]
b. PGH Section of Gynecologic Oncology Eligibility
Criteria for Radical Vaginal Hysterectomy:
1. Selected Stage 1B1 IIA (low risk for parametrial or nodal metastasis, tumor size less than 2 cm, no evidence
of metastasis by imaging and metastatic work-up)
2. Pelvic organ prolapse
c. Radical vaginal trachelectomy and laparoscopic/
extraperitoneal pelvic lymphadenectomy23 inclusion criteria:
1. Desire to preserve fertility
2. No clinical evidence of impaired fertility
3. FIGO Stage 1a2-1B1
4. Lesion size less than 2 cms
5. No evidence of pelvic lymph node metastasis
6. No LVSI
7. Informed consent
d. May proceed with RHBSO + lymphadenectomy
even with the presence of resectable lymph node
metastasis with uninvolved parametria.31,32




1. Concurrent chemotherapya and
pelvic EBRT + Brachytherapy
(Chemoradiation)b 6,33-35
[Level 1b]

2. Neoadjuvant chemotherapy
(three rapidly delivered courses
of platinum-based chemotherapy),
followed by RHBLND BSO +

adjuvant postoperative radiation
or chemoradiation36,37[Level 1b].
Chemotherapeutic options
a. Cisplatin-Paclitaxel
Stage IB 2 , II A b. Cisplatin Vinblastine
(tumor diameter Bleomycin (PVB)
>4 cms) c. Cisplatin Ifosfamide

3. Pelvic EBRT concurrent with
chemotherapya followed by

RHBSO with selective lympha denectomy (Level 2b)38 (Toral 2005)

4. Primary RHBSO and bilateral
pelvic lymphadenectomy, with
adjuvant chemoradiation1,39,40
(type of radiotherapy will be
dependent on the surgico-patho
logic factors) [Level 2B]

a. Standard chemotherapy drug to use for concurrent
treatment with radiotherapy:
Cisplatin 40 mg/ m2 given weekly for 6 courses during
pelvic EBRT1,4-9 [Level 1a]
b. Surgical intervention (EHBSO or Type II RHBSO)
is an option for the following cases:
1. After protracted chemoradiation (>8 weeks)38,41
(Level 2b)
2. Bulky residual disease (>2 cm) at the end of radiation therapy42,43
c. Pelvic EBRT (with no midline shield) concurrent with
chemotherapy followed by RHBSO with selective
lymphadenectomy is an option especially for areas
with no brachytherapy facilities (consensus-based)
d. Ongoing trial EORTC 55994 : Randomized phase
III study of neoadjuvant chemotherapy (3 courses
cisplatin based) followed by surgery vs. concomitant radiotherapy and chemotherapy in FIGO Ib2,
IIa >4 cm or IIb cervical cancer



Concurrent chemotherapya,b and

pelvic EBRT + Brachytherapy
Chemoradiation4-7,9,39,40 [Level 1a]

Stage IIB - IV

Paraaortic lymphadenopathy (size

>1.0 cm) by MRI, CT scan or PET
scan confirmed by FNA or extraperitoneal or laparoscopic lymphadenectomy: extended field radiotherapy (EFRT)+ brachytherapy
+ concurrent cisplatin chemo-

Cervical Cancer

therapy44-46 [Level 2A]

EBRT52[Level 1B]

If with evidence of distant metas-

tases on imaging and/or biopsy:
Systemic combination chemotherapy and individualized radiotherapy 1[Level 2A]

Concurrent chemotherapy, pelvic EBRT

and brachytherapy

a. Standard chemotherapy drug to use for concurrent
treatment with radiotherapy:
Cisplatin 40 mg/ m2 given weekly for 6 courses during
pelvic EBRT1,4-8 [Level 1a]
b. Other chemotherapy regimens used for concurrent
treatment with radiotherapy (For locally advanced
cervical cancer)
1. Carboplatin 300 mg/m2 (AUC 3.9) every 3 weeks
or 60-90mg/m2 (AUC 2) weekly47,48
2. Cisplatin 40 mg/m2 and Paclitaxel 40 mg/m2 weekly
for 6 cycles49
c. Ongoing trial GOG 219:A Phase III, Randomized
Trial of Weekly Cisplatin and Radiation Versus
Cisplatin and Tirapazamine and Radiation in Stage
IB2, IIA, IIB, IIIB and IVA Cervical Carcinoma Limited to the Pelvis
1. Histologic type
2. Histologic grade
3. Lymphovascular space involvement (LVSI)
4. Parametria
5. Vaginal cuff to include distance from tumor to margin
6. Stromal invasion divided into thirds
7. Endomyometrial invasion
8. Lymph nodes, to include number and location,
and/or Perinodal fat involvement
9. Adnexa, if BSO performed
10. For MICA, vertical and horizontal invasion in mm
11. For CIN/CIS post-conization (cold-knife or LEEP/
LLETZ), status of margins and +/- LVSI
12. Mark a cone specimen at the 12 oclock position
13. No mention of stage of disease in histopathologic
1. Tumor
size >2 cm**

Concurrent chemotherapy and
pelvic EBRT50,51 [Level Ib: 4 cms]
Consensus based

2. Greater than Concurrent chemotherapy and

1/3 stromal pelvic EBRT30,50,52 Delgado1990, Sedlis 1999,
[Level IB]

3. Positive
lines of

Concurrent chemotherapy and pelvic

EBRT52Delgado 1990
[Level 1B]

Concurrent chemotherapy and pelvic


Vaginal cuff
or <2 cm
tumor free

4. Lymph node Pelvic


Concurrent chemo-
therapy and pelvic
EBRT8,50,52-53 [Level 1B]

Note: If para-aortic
sampling not performed, may do EFRT
if MRI or CT Scan
confirms periaortic

Para-aortic Concurrent chemoand Common therapyandEFRT29,52-55

[Level 2A]

5. Lymphovascu- Concurrent chemotherapy and

cular space pelvic EBRT30,48,51,52 Delgado1990,

invasion (LVSI) Sedlis 1999, Rotman2006) [Level IB]
6. Endomyome- Concurrent chemotherapy and
trial invasion pelvic EBRT52[Level C]
7. Biopsy proven Systemic chemotherapy and Indivi abdominal
dualized radiotherapy52,53

[Level 2A]
1. Pathologic review
2. Chest x-ray
3. CTScan, MRI or PET Scan
4. Liver function tests
5. Renal function tests
6. If tumor size is more than 4 cms: cystoscopy/proctosigmoidoscopy

Pathologic Review


Stage 1A1, no LVSI

Observation 1 [ Level 2A]

Stage 1A1 with LVSI,

Stage 1A2 and IB1
Negative margins,
negative imaging studies

Concurrent chemotherapy
and pelvic EBRT +
Brachytherapy Chemoradiation54 [Level 2A]

Complete parametrectomy
with upper vaginectomy
with pelvic lymphadenec-
tomy +/-paraaortic lymph
node sampling54 [Level 2A]

Stage 1A1 with LVSI,

Stage 1A2 and above
Positive margins, gross
residual disease, positive
imaging studies

Concurrent chemotherapy
and pelvic EBRT + Brachytherapy chemoradiation55
[Level 2A]
If paraaortic lymphadenopathy: give EFRT55 [Level 2A]

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Cervical Cancer
B. In Association with Pregnancy
MRI may be done to assess extent of disease 10

Age of

Early Stage
(Stage I II A)

Late Stage
(Stage II B IV)

Good surgical risk
Pregnancy RHBLND BSO10

up to
20 weeks
Poor surgical risk


May delay treatment

till after delivery1
20-28 weeks


(Cisplatin based)

then CS1

Good surgical risk

28 weeks

*CS followed by

* Perform Poor surgical risk

CS followed by
Section (CS)10 Chemoradiation56 (Cisplatin based )
at best time
then CS56

of fetal


1. There is no standard definition on what constitutes
significant treatment delay.1
2. The duration of the treatment delay should be influenced by clinical stage and histopathologic findings
of the tumor, gestational age at diagnosis, and the
parents desire regarding their unborn child. Close
clinical surveillance is mandatory.1
3. No long term studies have looked into giving neoadjuvant chemotherapy in an attempt to prevent disease
4. Delivery should be performed not later than 34 weeks
of gestation.1
1. Age 45years old57
conservation [Level 2B]
during radical
2. Early stage disease
surgery in young (up to IIA)57,58 [Level 2B]
3. Squamous large cell histo logy57-58,61-64 [Level 2B]

4. Cervical stromal involve ment inner 1/357 [Level 2B]

5. No family history of ovarian
or breast cancer1,58

6. Tumor size 2 cm60,62

7. No lymph node metastasis
or LVSI60-64

8. Absence of extracervical/
corpus spread62,63

9. No gross abnormalities in
the ovaries62,63

10. No need for post operative radiation57,58,62,63


adnexal masses

Exploratory laparotomy
(EL), BSO and appropriate
surgical procedures as
indicated, before chemoradiation
Option: Laparoscopy

Primary cases
with urinary

Urinary diversion and/or

stenting followed by primary

Primary cases
with gut

Medical or surgical decompression followed by

primary treatment

(post RT)

tissue disease
(All stages
requiring RT)

Drainage by cervical
dilatation or EHBSO
Patients should be seen by the
Multidisciplinary Team, which
should ideally include a
Ideally, patients disease
should not be active at the
time of radiotherapy.


With prior surgery, no
prior radiotherapy

[Level 2A]

With prior radio-

therapy, central
disease with
tumor size 2 cm

Appropriate surgery (Type I

(Type I or II extended
hysterectomy) may be
performed1,66 [Level C] (if
adverse surgico-prognostic
factors are present, adjuvant
chemotherapy should be

With prior radiotherapy, Platinum-based chemo central disease with

therapy or best support tumor size > 2 cm and ive care1,44
noncentral disease

With prior chemo-
radiation, central
chemotherapy or best
disease with tumor
supportive care1,44
size >2 cm and non central disease

Multiple sites,

Isolated site

Systemic chemotherapy or
best supportive care1,44,67
[Level 2A]
Tumor resection44[ Level 2A]
Tumor directed radiotherapy44
[Level 2A]
Systemic chemotherapy or
best supportive care 1,44,67
[Level 2A]

Cervical Cancer
1. Chemotherapy may be given for palliative intent or
symptomatic care. Chemotherapeutic options include:
SINGLE AGENT1,44,68,69
a. Cisplatin [Level 1B] 50mg/m2 every 3weeks
b. Carboplatin [Level 1B]-50 mg/m2 every 3 weeks or
400mg/m2 every 3 weeks
c. Topotecan [Level 1B]-1.5mg/m2 days 1-5 every 4
d. Paclitaxel [Level 1B]- 170 mg/m2 for 24 hours every
3 weeks
a. Cisplatin Topotecan [Level 1B]- GOG 179 Cis 50
mg/m2 day 1, Topo 0.75 mg/m2 days 1-3 every 3
b. Cisplatin Paclitaxel [Level 1B]- GOG 169 Cis 50 mg/m2
day 1, Pacli 135 mg/m2 24 hours 3 weeks
c. Cisplatin-Ifosfamide [Level 1B] GOG 110 Cis 50 mg/m2
day 1, Ifos: 5 gm/m2/24 hours every 3 weeks
d. Cisplatin Gemcitabine [Level 2b] Cis 70 mg/m2
day 1, Gemcitabine 1.25 mg/m2 day 1, 8 every 3
e. Cisplatin- Irinotecan [Level 2b] Cis 50mg/m2, CPT11 100mg/m2 every 3 weeks
f. Cisplatin Vinoralbine [Level 2b] Cis 75 mg/m2 Vin
30 mg/m2 every 4 weeks
g. Carboplatin-Paclitaxel [Level 2b] Carbo AUC 5-6
day pacli 155-175mg /m2 every 4 weeks
h. Topotecan-Paclitaxel [Level 2b] Pacli 175 mg/m2
day 1, topo 1 mg/m2 days 1-5 every 3 weeks
2. Combination regimens are preferred and are first line
therapy if Cisplatin was previously used as a radiosensitizer
3. Ongoing Trial GOG204-A Randomized Phase III Study
of Paclitaxel plus Cisplatin Versus Vinorelbine Plus
Cisplatin Versus Gemcitabine Plus Cisplatin Versus
Topotecan Plus Cisplatin in Stage IVB, Recurrent or
Persistent Carcinoma of the Cervix


Hormone therapy may be given to symptomatic women
who have been treated for cervical cancer.
1. HRT significantly reduced long term post radiation
rectal, bladder and vaginal complications71
2. There is no evidence that HRT increases risk of squamous cell carcinoma. For adenocarcinoma, a risk
of recurrence is noted in a descriptive study72.
1. Benedet JL, Pecorelli, S, Hacker NF, Ngan HYS. Staging Classifications
and Clinical Practice Guidelines of Gynecologic Cancers by FIGO
Committee on Gynecologic Oncology and IGCS Guidelines Committee,
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2. Hricak H, Gatsonis C, Chi DS et al. Role of Imaging in the Pretreatment
evaluation of early invasive cancer: Results of the Intergroup Study
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4. Whitney CW, Sause W, Bundy BN, et al. Randomized comparison
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adjuvant hysterectomy for bulky stage IB cervical carcinoma. New
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8. Peters WAI, Liu PY, Barrett R, et al. Cisplatin, 5-Fluorouracil plus
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1. Weekly while on concurrent chemotherapy and radiotherapy.
2. Two (2) weeks post-completion of brachytherapy.
3. After completion of treatment, recommended follow-up
is as follows:
a. Physical and pelvic exams every 3 months for the
first 2 years, every 6 months from years 3-5, then
yearly thereafter.70
b. Pap smear every three months for the first 2 years,
followed by pap smear every six months for the 3rd
5th year, then annual pap smear thereafter.
NOTE: Perform colposcopy with appropriately
guided biopsy and/or ECC, as warranted.
c. Chest x-ray annually or as indicated70.
d. An annual CT scan, MRI or PET scan for the first
3 years post-treatment is recommended, or when
4. Use of a vaginal dilator is suggested after radiotherapy
for women who are sexually active70 Denton 2003 systematic review.

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Learn to access drug info on your cellphone. Send PPD to 2600 for Globe/Smart/Sun users.


Cervical Cancer
Available Drugs in the Philippines
Alkaylating Agents
Nippon Kayaku Cisplatin
Pyrimidine analogs
(Pyrimidine antagonists)
Other cytotoxic antibiotics
Bleomycin sulfate
Mitotic Inhibitors
Vinca Alkaloids
Topotecan HCl
Biomedis Paclitaxel
Sandoz Paclitaxel
Biomedis Irinotecan