Sgop 2012

Society of Gynecologic Oncologists of the Philippines
(Foundation), Inc.
Clinical Practice Guidelines
Sixth Edition
November 2012
A Recognized Affiliate Subspecialty Society of P GS

SGOP TREATMENT GUIDELINES 2012
TABLE OF CONTENTS
Page No
Message from the POGS President
Foreword
Preamble
SGOP Officers 2011-2012
PBGO 2011-2012
SGOP General Membership
Ad Hoc Committee for the Clinical Practice Guidelines 2012
CLINICAL PRACTICE GUIDELINES
Cervical Cancer
Endometrial Cancer
Uterine Sarcoma
Ovarian Cancer
Fallopian Tube Cancer
Vulvar Cancer
Vaginal Cancer
Preventive and Treatment of Complications
Cancer Pain Management
APPENDIX
Appendix A – Levels of Evidence and Grades of Recommendation
Appendix B – Geographical Distribution of Gynecologic Oncologists
Appendix C – 2009 FIGO Staging of Gynecologic Malignancies
Appendix D – Useful Markers in Gynecologic Pathology
Appendix E - Differential Diagnosis by Immunohistochemistry
Appendix F – Definition of Response to Treatment
Appendix G – Performance Status Scoring
Appendix H – Useful Web Addresses

MESSAGE FROM THE POGS PRESIDENT
The field of obstetrics and gynecology is a very dynamic one. Numerous

discoveries, inventions and innovations are uncovered every now and then. As a
responsible medical practitioner we should always update ourselves to be abreast
with what is the current standard of optimum care.
My heartfelt congratulations to the Society of Gynecologic Oncologists of the
Philippines [SGOP] (Foundation), Inc., for their initiative in always updating the
Clinical Practice Guidelines (CPG) in Gynecologic Oncology. Every edition of the
CPG involves hard work and tedious scrutiny by a committee composed of
specialists of the field and approved in a plenary session made up of its the
stakeholders. This is a testimony of your fervent desire to uplift the practice of
gynecology, particularly, gynecologic oncology. This will go a long way in making our
members abreast on what is new in this field. I sincerely hope that the knowledge
gained from this CPG will guide not only the gynecologic oncology practitioners but
also the general obstetrician and gynecologist so that they will be able to confidently
advise and give the best care to their patients.
It is with utmost sincerity that I congratulate and laud the SGOP for this
noteworthy endeavor. It is my fervent hope that you will never cease to be a staunch
partner of POGS in its campaign to provide continuing medical education to our
members and the gynecologic oncology fellows and residents on training, to be of
better service to the patients we serve.
REY H. DELOS REYES, MD, MHSA, FPOGS, FSGOP, FPSCPC

President
Philippine Obstetrical and Gynecological Society (Foundation), Inc.

FOREWORD
Providing the best standard of care for gynecologic cancer patients is one of the
main objectives of the Society of Gynecologic Oncologists of the Philippines [SGOP]
(Foundation), Inc. In this regard, the Society has regularly updated its Clinical
Practice Guidelines (CPG), generally every three years. In 2011, the local CPG was
scheduled for revision. However, because of the ongoing modification of the
International Federation of Obstetrics and Gynecology (FIGO) staging system, it was
put on hold pending the final product. The following year saw the official publication
of the 2009 FIGO staging guidelines, with entirely new staging for uterine sarcomas,
significant changes in endometrial cancer, and minor changes for cervical and vulvar
cancers.
Although at this time the SGOP Committee on CPG was already starting the
groundwork for the revision, it had to wait for the corresponding treatment regimens
based on the new staging. Finally, the various international societies and institutions
came out with their management programs. These new literature were all thoroughly
reviewed and appropriate adaptations were made for the local setting. The draft
2012 SGOP CPG was presented by the Committee to the general membership
during the Midyear Convention in Laoag City, where it was approved unanimously.
I am certain that this handbook will serve as a ready reference for physicians who
take care of women who are at risk of developing, or who are afflicted with malignant
conditions of the genital tract. I am profoundly grateful to the Adhoc Committee on
CPG for the expertise, time, and effort they devoted to this current version.
GIL S. GONZALEZ, MD, FPOGS, FSGOP, FPSCPC

President
Society of Gynecologic Oncologists of the Philippines [SGOP] (Foundation), Inc.

PREAMBLE
• The clinical recommendations contained in this manuscript is the sole ownership

of the Society of Gynecologic Oncologists of the Philippines, Inc (SGOP).
• The contents of the individual chapter/s passed the standard process of study,
derivation and consultation, including plenary approval and criticquing.
• The Gynecologic Oncologist member of the SGOP is the recommended user of
this Clinical Practice Guidelines (CPG).
• The other users of this CPG are advised to comprehend the contents and
recommendations with caution, in all aspects, particularly on actual therapeutic
intervention which is solely the domain of the certified Gynecologic Oncologist
of the SGOP.
• The student of Obstetrics and Gynecology, the trainees of both Obstetrics and
Gynecology and Gynecologic Oncology are advised to study the contents of this
CPG with much detail and restraint. Restraint on the part of the references which
have always been the most recent. There are, however, clinical recommendations
based on “consensus” which will purely remain, and is in its purest form, a
“consensus derived from general, sound, clinical experience, with safety and
good outcomes”.
• The right to quote, to publish, to cite and to duplicate belongs only to the SGOP.
Whatever reference to the contents that may be made by the user of this CPG,
this should be governed by existing laws on copyright and publication.
• Without the intent to be litiginous in any forum, the recommendations cited
herein are not supposed to be the ultimate truth, the unfallible bases, the prime
correct treatment. But these constitute only recommendations which may or may
not be observed, followed and implemented. It may vary from case to case, it
may not be applicable in all situations/cases. The truth is, the only correct case in
fact is the case itself, not only this CPG.
• It is hoped by the SGOP, and all the authors of this CPG that this will be used in
order to farther the art and science of Gynecologic Oncology. To be able to
advance healing and cure in the majority of the diseases handled by the
subspecialty. It is hoped that this endures and be revised continually after every
specified period until the subspecialty sees its good and defined purpose.
EFREN J. DOMINGO, MD,PhD, FPOGS, FSGOP, FPSCPC

Past President, SGOP
Chair, Ad Hoc Committee for the SGOP Clinical Practice Guidelines

THE SOCIETY OF GYNECOLOGIC ONCOLOGISTS OF THE PHILIPPINES,
(FOUNDATION) INC.
OFFICERS
2011 – 2012
GIL S. GONZALEZ, MD
President
CECILIA L. LLAVE, MD, PhD

Vice-President
MA. JULIETA V. GERMAR, MD

Secretary
MA. LILIBETH L. SIA SU, MD

Treasurer
JOCELYN Z. MARIANO, MD
PRO
REY H. DELOS REYES, MD, MHSA

Immediate Past President
BOARD OF DIRECTORS
Teresita B. Cardenas, MD Jericho Thaddeus P. Luna, MD
Lilli May T. Cole, MD Mary Christine F. Palma, MD
Benjamin D. Cuenca, MD Ma. Cynthia F. Tan, MD
Aris Luke I. Dungo, MD Jean Anne B. Toral, MD
PHILIPPINE BOARD OF GYNECOLOGIC ONCOLOGY
Cecilia L. Llave, MD, PhD

Chairman
Members
Virgilio R. Oblepias, MD
Concepcion D. Rayel, MD

THE SOCIETY OF GYNECOLOGIC ONCOLOGISTS OF THE PHILIPPINES
[SGOP]
(FOUNDATION), INC.
2012 GENERAL MEMBERSHIP

FELLOWS
ABAD, Rainerio S. DUEÑAS, Rommel Z. OBLEPIAS, Virgilio R.

AGBANLOG, Teresita P. DUNGO, Aris Luke I. PALMA, Mary Christine F.
AQUILIZAN, Leo Francis N. EVANGELISTA, Emilio Glenn B. PUA, Scheryll B.
ARIAS, Coleta B. FAMADOR, Jay Arnold F. RAÑOLA, Rona F.
ANTINERO, Belina A. FLAVIER, Carol Marjorie P. RAYEL, Concepcion D.
BADILLA, Edelyn A. FERNANDO, Victoria S. RIVERA, Wilhelmina D.
BANTA, Edna C. GADDI, Agnes M. SABADO, Grace D.
BAUTISTA, Aida J. GALBO, Pherdes E. SAN JUAN, Filomena S.
BENAVIDES, Doris R. GANZON, Esther Rhadamanthine V. Jr. SANTOS, Elmer R.
BENITEZ, Glenn B. GARANA, Belen T. SANTOS, Helen Grace T.
BENITEZ, Isidro B. GARCIA, Christine Joy G. SIA SU, Maria Lilibeth L.
BORJA, Manuel N. † GARCIA, Victorino C. Jr. SICAM, Renee Vina G.
BRESNAN, Alma M. GERMAR, Maria Julieta Corazon V. SOLIS, Constancia Wilhelmina T.
BUIZON, Andrew Rouldan B. GONZALEZ, Ma. Gay M. SORIANO, Yvonne T.
CABANELA, Judith G. GONZALEZ, Gil S. SOTTO, Luciano S.J. Sotto
CACHO, Richard Ronald B. HUEVOS, Arlene B. SOTTO, Rene V.
CAMPOS, Ronald Agustine O. LIMSON, Genara M. STREBEL, Elizabeth E.
CARDENAS, Teresita B. LIWAG, Arnold P. SULAY, Raymond S.
CASTRO, Carolyn Z. LLAVE, Cecilia L. SUN, Patricia L.
CAYABYAB, Melinda M. LUNA, Jericho Thaddeus P. TAGAYUNA, Irene M.
COCOS, Percida S. MADURAMENTE, Myra Joy G. TAN, Ma. Cynthia F.
COLE, Lilli May T. MALIG, Marie Aleli D. TAN CARDOSO II, German C.
CORONEL, Patricia Ann S. MANABAT, Manuel S. TORAL, Jean Anne B.
CRISTOBAL, Ruth Judith V. MANALO, Augusto M. † TUPAS, Ma. Lora C.
CUENCA, Benjamin D. MARIANO, Jocelyn Z. VALDEZ, Corazon R.
DANCEL, Elsie, R. MERCADER, Evangeline M. VILLADELGADO, Menandro A.
DELA CRUZ, Melchor C. Jr. MERCADO, Fe Marissa G. VILLANUEVA, Salvador Luis R.
DELOS REYES, Rey H. MERCADO, Mary Evangeline V. YAMBAO, Helen D.
DIAZ, Aina S. MORAN, Jose B. ZAMORA, John David V.
DOMINGO, Efren J. MOTIL, Gina P.
DIPLOMATES
DY ECHO, Ana Victoria V. TAN, Jaynet D. AMPARO, Genalyn F.
AFFILIATES
ABELARDO, Agustina D. DALMACIO-CRUZ, Adelaida D. ORTIN, Teresita S.

AVILA, Jose Ma. C. DULAY, Robert P. PADILLA-CRUZ, Angeles †
CABALUNA, Ma. Lourdes Josefina K. JACINTO, Elizabeth K. PALO-GARCIA, Fe L.
CALAGUAS, Miriam Joy C. JOCSON, Milagros T. QUEVEDO, Ma. Carmen H.
CANLAS, Benjamin D. † LOPEZ, Rolando A. TAN, Eduardo G.
CAPITO, Lourdes B. MANALASTAS, Ricardo M. Jr. TRINIDAD, Anne Marie L.
CHAN, Valorie F. NARCISO, Francisco V. VEGA, Gaudencio P.
CRUZ, Bernadette O. NGELANGEL, Corazon A. ZAMUCO, Jaime T.
NUQUI, Elizabeth A.
HONORARY FELLOWS
CHANNEN, William PECORELLI, Sergio THOMAS, Gillian M.

MANAHAN, Constantino P. † FRIEDLANDER, Michael

AD HOC COMMITTEE FOR THE SGOP 2012 CLINICAL PRACTICE
GUIDELINES
CHAIR
Efren J. Domingo, M.D., Ph.D.
COORDINATORS
Jericho Thaddeus P. Luna, M.D.
Maria Julieta V. Germar, M.D.
Ana Victoria V. Dy Echo, M.D.
CERVICAL CANCER
Efren J. Domingo, M.D., Ph.D.
Maria Julieta V. Germar, M.D.
Fellows
Jaynet dC. Tan, M.D.
Maria Margarita M. Montecillo, M.D.
Quenny Michelle Dyan A. Alas, M.D.
ENDOMETRIAL CANCER & UTERINE SARCOMAS

Jericho Thaddeus P. Luna, M.D.
Carolyn R. Zalameda-Castro, M.D.
Fellows
Grace Q. Madis, M.D.
Rommel A. Garcia, M.D.
Merlind M. Morales, M.D.
OVARIAN & FALLOPIAN TUBE CANCERS

Ma. Lilibeth L. Sia Su, M.D.
Jean Anne B. Toral, M.D.
Fellows
Anna Katrina I. Sobritchea, M.D.
Angelito dL. Magno, M.D.
Ronald R. Latap, M.D.
VULVAR & VAGINAL CANCERS

Glenn B. Benitez, M.D.
Doris R. Benavides, M.D.
Fellows
Carlos Ray B. Sanchez III, M.D.
Ronald B. Capito, M.D.
Divina Ghea B. Mata, M.D.
PAIN
Ma. Lourdes Josefina K. Cabaluna, M.D.
PREVENTION & TREATMENT OF COMPLICATIONS

Filomena S. San Juan, M.D., Ph.D.
Cecila L. Llave, M.D., Ph.D.
Ana Victoria V. Dy Echo, M.D.
Fellow
Rose Joy C. David-Vallega, M.D.

CERVICAL CANCER
GENERAL GUIDELINES
1. Cervical cancer is diagnosed by biopsy.1
2. Cervical cancer is staged clinically. All recommendations are based on the

2009 International Federation of Gynecology and Obstetrics (FIGO)
definitions and staging.2
3. If clinically indicated, proctosigmoidoscopy and cystoscopy should be done to

rule out bladder/bowel invasion. Metastatic work-up include imaging studies,
renal function tests, liver function tests, kidney urinary bladder intravenous
pyelography (KUB IVP), barium enema and chest x-ray.
4. Special diagnostic imaging studies may be done to guide treatment planning:

ultrasound, magnetic resonance imaging (MRI), computed tomography (CT)
scan, positron emission tomography (PET) scan, PET-CT scan and bone
scintigraphy.1 Imaging is optional for patients with stage IB1 tumor or smaller.
These imaging studies will not be part of the staging.
a. MRI is more accurate than CT scan in determining the following:3
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, extrapelvic
metastases and in detecting recurrence.3,4
5. The roles of laparoscopic or robotic surgery in staging and treatment need

well-designed randomized controlled trials.
6. The primary treatment of early stage cervical cancer is either surgery or

concurrent chemotherapy and complete radiotherapy (chemoradiation).5-11
7. The primary treatment of late stage cervical cancer is concurrent

chemotherapy and complete radiotherapy (chemoradiation).11
8. For patients who are unable to receive chemotherapy, radiation treatment

alone may be given.11
9. Lymphovascular space invasion (LVSI) does not alter the FIGO

classification.2
10. Adenocarcinomas have shown no significant difference in clinical behavior

from squamous cell carcinomas.9,10

MANAGEMENT
I. Biopsy Proven Premalignant Lesions12

LESION TREATMENT
SATISFACTORY UNSATISFACTORY
COLPOSCOPY COLPOSCOPY
1. Preceded by ASCUS, ASC-H, Diagnostic excisional
LSIL: Follow up every 6-12 procedures12 [Level 3a]
12,13
CIN 1 months [Level 2b]
2. Preceded by HSIL, AGC:
Follow up every 6 months OR
Diagnostic excisional
procedures12,13 [Level 3b]
1. Cryotherapy12 [Level 1a] Diagnostic excisional
CIN 2,3 2. Diagnostic excisional procedures12,14,15 [Level 2a]
12,14,15
procedures [Level 1a]
*CIN – cervical intraepithelial neoplasia; ASCUS – atypical squamous cells of undetermined significance; ASC-H –
atypical squamous cells cannot exclude high grade squamous intraepithelial lesion; LSIL – low grade squamous
intraepithelial lesion; HSIL – high grade squamous intraepithelial lesion; AGC – atypical glandular cells
Notes: Diagnostic excisional procedures include the following: cold-knife conization

(CKC), loop electrosurgical excision procedure (LEEP) or large loop excision of the
transformation zone (LLETZ).12
II. Malignant Disease

The following guidelines apply to squamous cell carcinoma, adenosquamous
carcinoma and adenocarcinoma of the cervix.
STAGE STATUS TREATMENT
1. Desirous of pregnancy, no LVSI
a. Negative margins – observe1,16-20 [Level 1b]
b. Positive margins – repeat cone biopsy1,16-20
[Level 1b]
Good surgical risk 2. Not desirous of pregnancy
a. EH ± BSO1,16-20 [Level 1b]
b. Vaginal EH ± BSO16 [Level 1b]
a
Stage IA1 c. If positive for LVSI: mRH ± BSO with
BLND1,16,22 [Level 2b]
1. Negative margins – observe1,16-21 [Level 1b]
2. Positive margins
a. Repeat CKC/LEEP1,16-20
Poor surgical risk b. Brachytherapy (intracavitary radiotherapy):
HDR or LDR
3. Positive LVSI: pelvic EBRTb + Brachytherapy
[Level 3c]
1. Desirous of pregnancy
a. Radical vaginal or abdominal trachelectomyc
and pelvic lymphadenectomy (extraperitoneal or
Good surgical risk transperitoneal, laparotomy or laparoscopy)24-26
a
Stage IA2 [Level 2b]
2. Not desirous of pregnancy
RH, BLND ± BSO17,26 [Level 1b]
Pelvic EBRTb + Brachytherapy [Complete RT]23
Poor surgical risk
[Level 2b]

*EH – extrafascial hysterectomy; BSO – bilateral salpingo-oophorectomy; mRH – modified RH; BLND – bilateral
pelvic lymph node dissection; HDR – high dose rate; LDR – low dose rate; EBRT – external beam radiotherapy;
RH – radical hysterectomy
Notes:
a. Stages IA1 and IA2 are diagnosed by diagnostic excisional procedures.1
b. Pelvic EBRT includes the upper half of the vagina. The use of CT-based
treatment planning and conformal blocking is considered standard of care for
EBRT.
c. Radical trachelectomy inclusion criteria26:
1. Informed consent
2. Desire to preserve fertility
3. No clinical evidence of impaired fertility
4. FIGO Stage IA2-IB1-IIA1
5. Lesion size less than 2 cms
6. No evidence of lymph node metastasis
7. No LVSI
STAGE STATUS TREATMENT

1. RH, BLND ± PALS ± BSO27-28 [Level 1a]
2. Concurrent chemotherapya and pelvic EBRT
+ Brachytherapy (Chemoradiation)29,30 [Level
1a]
3. Radical vaginal hysterectomy (Schauta) ±
Good surgical risk BSO and extraperitoneal or laparoscopic
pelvic lymphadenectomyb 31,32 [Level 1c]
Stage IB1,
4. Nerve-sparing RH, BLND ± PALS ± BSO
IIA1
Level 2b33
5. Radical vaginal or abdominal trachelectomy
and pelvic lymphadenectomy (extraperitoneal
or transperitoneal, laparotomy or
laparoscopy) 23-26 [Level 2b]
Concurrent chemotherapya and pelvic EBRT +
Poor surgical risk Brachytherapy (Chemoradiation)29,30
[Level 1a]
*PALS – para-aortic lymph node sampling
Notes:
a. Standard chemotherapy drug to use for concurrent treatment with radiotherapy
(chemoradiation): Cisplatin 40 mg/m2 given weekly during pelvic EBRT1,5-10
[Level 1a]
b. PGH Section of Gynecologic Oncology Eligibility Criteria for Radical Vaginal

Hysterectomy (Schauta):
1. Selected stage IB1-IIA1 (low risk for parametrial or nodal metastasis, tumor
size less than 2 cm, no evidence of metastasis by imaging and metastatic
work-up)
2. Stage IB1-IIA1 with pelvic organ prolapse
c. May proceed with RHBSO + lymphadenectomy even with the presence of lymph
node metastasis, if surgically resectable and with uninvolved parametria.34,35

STAGE TREATMENT
1. Concurrent chemotherapy and pelvic EBRT + Brachytherapy
(Chemoradiation)a,b 7,36-38 [Level 1b]
2. Neoadjuvant chemotherapy (three rapidly delivered courses of
platinum-based chemotherapy), followed by RHBLND ± PALS
± BSO + adjuvant postoperative radiation or
chemoradiation39,40 [Level 1b]
Neoadjuvant chemotherapeutic options include:
a. Cisplatin-Paclitaxel41
Stage IB2, IIA2
b. Cisplatin-Ifosfamide
c. Cisplatin-Topotecan42
3. Concurrent chemotherapy and pelvic EBRT followed by
RHBSO + PALS and selective pelvic lymphadenectomy43-48
[Level 2b]
4. Primary RHBSO, BLND + PALS which usually needs to be
followed with adjuvant chemoradiation1,49,50 (type of
radiotherapy will be dependent on the surgico-pathologic
factors) [Level 2b]
Notes:
a. Standard chemotherapy drug to use for concurrent treatment with radiotherapy:
Cisplatin 40 mg/m2 given weekly during pelvic EBRT1,5-9 [Level 1a]
b. Surgical intervention (EHBSO or mRHBSO) is an option for the following cases:

1. After protracted chemoradiation (> 8 weeks)43,45 [Level 2b]
2. Bulky residual disease (> 2 cm) at the end of radiation therapy44,46-47
c. Concurrent chemotherapy and pelvic EBRT (with no midline shield) followed

by RHBSO + PALS and selective pelvic lymphadenectomy is an option
especially for areas with no brachytherapy facilities44 [GPP]
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, IIA2 or IIB cervical cancer.
STAGE TREATMENT
a,b
Concurrent chemotherapy and pelvic EBRT + Brachytherapy
(Chemoradiation)5-8,10,11 [Level 1a]
Paraaortic lymphadenopathy (size > 1.0 cm) by MRI, CT scan or
PET scan confirmed by FNA or extraperitoneal or laparoscopic
Stage IIB - IV lymphadenectomy: EFRT + Brachytherapy + concurrent platinum-
based chemotherapy50-52 [Level 2a]
If with evidence of distant metastases on imaging and/or biopsy:
a. If multiple/unresectable: chemotherapy or best supportive care50
b. If resectable: metastesectomy + chemotherapy, RT or
chemoradiation 50 [Level 2a]
*FNA – fine needle aspiration; EFRT – extended field radiotherapy
Notes:
a. Standard chemotherapy drug to use for concurrent treatment with radiotherapy:
Cisplatin 40 mg/m2 given weekly during pelvic EBRT1,5-9 [Level 1a]

b. Other chemotherapy regimens that can be used for concurrent treatment with
radiotherapy (for locally advanced cervical cancer)
1. Cisplatin 40 mg/m2 and Gemcitabine 125 mg/m2 weekly for 6 weeks during
pelvic RT and then 2 adjuvant cycles of Cisplatin 50 mg/m2 on day 1 plus
Gemcitabine 1000 mg/m2 D1,8 every 21 days53 [GRADE PRO: HIGH]
2. Carboplatin 300 mg/m2 (AUC 3.9) every 3 weeks or 60-90 mg/m2 (AUC 2)
weekly54,55
3. Cisplatin 40 mg/m2 and Paclitaxel 40 mg/m2 weekly for 6 cycles56
4. Capecitabine 825 mg/m2 twice daily (Monday to Friday, weeks 1-8) during
radiation followed by 6 cycles of Capecitabine 1,000 mg/m2 twice daily D1-14
every 21 days.57
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 pelvis50
FINAL HISTOPATHOLOGY REPORT OF CERVICAL CANCER SPECIMENS

1. Histologic type
2. Histologic grade
3. Presence or absence of 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 microinvasive carcinoma (MICA), vertical and horizontal invasion in mm
11. For CIN/carcinoma in situ (CIS) post-excision (CKC or LEEP/LLETZ), status
of margins and presence or absence of LVSI
12. Mark a cone specimen at the 12 o’clock position
13. No mention of stage of disease in histopathologic reports
SURGICO-PATHOLOGIC PROGNOSTIC FACTORS
PROGNOSTIC FACTORS ADJUVANT TREATMENT

1. Tumor size > 2 cm Concurrent chemotherapy and pelvic EBRT58,59
[GPP]
2. Greater than 1/3 stromal Concurrent chemotherapy and pelvic EBRT58,60
invasion [Level IB]
3. Positive lines of Parametrium Concurrent chemotherapy
resection and pelvic EBRT58
[Level 1b]
Surgical margins Concurrent chemotherapy
and pelvic EBRT58
[Level 1b]
Vaginal cuff or < 2 cm Concurrent chemotherapy,
tumor free margin pelvic EBRT and
brachytherapy [GPP]

4. Lymph node metastasis Pelvic Concurrent chemotherapy
and pelvic EBRT9,50,58,59
[Level 1b]
Note: If PALS not

performed, may do EFRT if
MRI, CT scan or PET scan
confirms periaortic
lymphadenopathy.
Para-aortic and Do chest CT scan or PET-
Common iliac CT scan
If no distant metastases:
Concurrent chemotherapy
and EFRT50,60-61 +
Brachytherapy [Level 2a]
If with distant metastases:

Chemotherapy 50 and
tailored RT
5. LVSI Concurrent chemotherapy and pelvic EBRT 58,60
[Level 1b]
6. Biopsy proven Systemic chemotherapy and tailored
abdominal metastasis radiotherapy50,60 [Level 2a]
SPECIAL CLINICAL SITUATIONS
A. INCIDENTAL FINDING OF INVASIVE CERVICAL CANCER AFTER SIMPLE

HYSTERECTOMY
1. Pathologic review
2. Chest x-ray
3. CT scan, MRI or PET-CT scan
4. Liver function tests
5. Renal function tests
6. If tumor size is more than 4 cm: cystoscopy/proctosigmoidoscopy
Pathologic Review Result Treatment

Stage IA1, no LVSI Observation1 [Level 2a]
Stage IA1 with LVSI, Stage IA2 and IB1 Concurrent chemotherapy and pelvic
Negative margins, negative imaging EBRT + Brachytherapy
studies (Chemoradiation)62 [Level 2a]
Radical parametriectomy with upper
radical vaginectomy with BLND +
PALS62 [Level 2a]
Stage IA1 with LVSI, Stage IA2 and Concurrent chemotherapy and pelvic
above EBRT + Brachytherapy
Positive margins, gross residual disease, (Chemoradiation)63 [Level 2a]
positive imaging studies
If with paraaortic lymphadenopathy: give
Concurrent chemotherapy and EFRT
(instead of EBRT) + Brachytherapy63
[Level 2a]

B. IN ASSOCIATION WITH PREGNANCY
General Principles:
1. The 2009 FIGO staging applies.

2. To evaluate hydronephrosis and/or pelvocaliectasia, KUB UTZ may be done.
3. MRI may be done to assess extent of disease.11
4. If highly considering pulmonary metastases, a chest x-ray with abdominal shield
may be done.11
5. Management is affected by the following factors:11
a. FIGO stage and tumor size
b. Nodal status
c. Histologic subtype of the tumor
d. Gestational age at diagnosis
e. Patient’s wishes/informed consent
Age of Gestation: Early Pregnancy up to 20 weeks AOG11

Stage Good Surgical Risk Poor Surgical Risk Pregnancy is desired
IA1, IA2 Delay in treatment acceptable

IB1, IIA1 RHBLND ± BSO ± Concurrent May delay treatment. May
PALS chemoradiation do CS at 34-36 weeks
AOG following antenatal
corticosteroids and
documentation of fetal lung
maturity
IB2-IIA2 Concurrent chemoradiation May give neoadjuvant
chemotherapya then may
do CS at 34-36 weeks
AOG following antenatal
corticosteroids and
documentation of fetal lung
maturity
IIB-IVA Concurrent chemoradiation
IVB Systemic chemotherapy, Palliative radiotherapy
*CS – cesarean section; AOG – age of gestation
Age of Gestation: above 20 weeks11

Stage Management at 20-28 weeks Management above 28 weeks
AOG AOG will depend on best time of
fetal survival in your hospital
IA1, IA2 Delay in treatment acceptable1,11 Delay in treatment acceptable
IB1, IIA1 May delay treatment. May do CS- May do CS-RHBLND ± BSO ± PALS
RHBLND ± BSO ± PALS at 34-36 or may delay treatment and do CS-
weeks AOG following antenatal RHBLND ± BSO ± PALS at 34-36
corticosteroids and documentation weeks AOG following antenatal
of fetal lung maturity corticosteroids and documentation of
fetal lung maturity
IB2-IIA2 May give neoadjuvant May do CS-RHBSO, BLND ± PALS
chemotherapy then may do CS- or may delay treatment and give
RHBSO, BLND ± PALS at 34-36 neoadjuvant chemotherapy then do
weeks AOG following antenatal CS-RHBSO, BLND ± PALS at 34-36
corticosteroids and documentation weeks AOG following antenatal

of fetal lung maturity corticosteroids and documentation of
fetal lung maturity
IIB-IVA Concurrent chemoradiation* May do CS then concurrent
*Individualize depending on chemoradiation
informed consent and survival rate
of preterm births in your hospital.
IVB Systemic chemotherapy, Palliative May do CS then systemic
radiotherapy chemotherapy and palliative
Individualize depending on radiotherapy
informed consent and survival rate
of preterm births in your hospital.
Notes:
a. There is no standard definition on what constitutes significant treatment delay.11
b. Close clinical surveillance is mandatory.11
c. No long term studies have looked into giving neoadjuvant chemotherapy in an
attempt to prevent disease progression.
d. Antenatal chemotherapy may be given in the form of Cisplatin or Cisplatin-
Paclitaxel.11,64
e. Antenatal chemotherapy may be given beyond the first trimester and up to less
than 2 weeks prior to delivery.11
C. OTHER CLINICAL SITUATIONS
a. Ovarian conservation 1. Age ≤ 45 years old66 [Level 2b]

during radical surgery in 2. Early stage disease (up to IIA1)66,67 [Level 2b]
young patients66 3. Squamous large cell histology66-68,70-73 [Level 2b]
4. Cervical stromal involvement inner 1/366 [Level 2B]
5. No family history of ovarian or breast cancer1,66
6. Tumor size ≤ 2 cm69,71
7. No lymph node metastasis or LVSI69-73
8. Absence of extracervical/corpus spread71,72
9. No gross abnormalities in the ovaries71,72
10. No need for postoperative radiation66,67,71,72
b. Non-metastatic adnexal EL, BSO and appropriate surgical procedures as
masses indicated, before chemoradiation
Option: Laparoscopy or Robotic Surgery
c. Metastatic adnexal 1. If within the field of radiation, may give
masses chemoradiation then reassess50
2. If there is extension above the field of radiation and
resectable, consider surgical removal (same as in
non-metastatic adnexal masses) or
chemoradiation or chemotherapy50
d. Primary cases with Urinary diversion and/or stenting followed by primary
urinary obstruction treatment11
e. Primary cases with gut Medical or surgical decompression followed by primary
obstruction treatment
f. Hemato-/hydro-/ Drainage by cervical dilatation or EHBSO
pyometra (post RT)
g. Connective tissue Patients should be seen by the Multidisciplinary Team,
disease (All stages which should ideally include a rheumatologist.
requiring RT) Ideally, patient’s connective tissue disease should not
be active at the time of chemoradiation.

h. Elderly patients (age 65 Concurrent chemoradiation can be given to elderly
years and above ) patients with ECOG < 2 because it does not increase
the risk of thromboembolic disease, fistula formation,
cystitis/proctitis, pelvic necrosis, ureteral obstruction,
and bowel obstruction50,74 [Level 2b]
EL – exploratory laparotomy; ECOG – Eastern Cooperative Oncology Group
PERSISTENT OR RECURRENT DISEASE
PELVIC
With prior surgery, no prior radiotherapy Chemoradiation1,50,75 [Level 2a]
With prior radiotherapy or Appropriate surgery (EHBSO or
chemoradiation, central disease with mRHBSO) may be performed1,76 [Level
tumor size ≤ 2 cm C]
(If adverse surgico-prognostic factors are
present, adjuvant chemotherapy should
be instituted) [GPP]
With prior radiotherapy, central disease Platinum-based chemotherapy or best
with tumor size > 2 cm and noncentral supportive care1,50
disease
With prior chemoradiation, central Nonplatinum-based chemotherapy or
disease with tumor size > 2 cm and non- best supportive care1,50
central disease
EXTRAPELVIC OR PARAAORTIC
Multiple sites, unresectable Systemic chemotherapy or best
supportive care1,50,77 [Level 2a]
Isolated site Tumor resection50 [Level 2a] AND/OR
Tumor directed radiotherapy50 [Level 2a]
AND/OR Systemic chemotherapy
OR Best supportive care1,50,77 [Level 2a]
Notes:
a. Chemotherapy may be given for palliative intent or symptomatic care.
b. If cisplatin was used as a radiosensitizer, combination platinum-based regimens
are preferred over single agents.77,78 [Level Ia]
c. Chemotherapeutic options include:
SINGLE AGENT1,50,79,80
1. Cisplatin 50 mg/m2 every 3 weeks [Level 1b]
2. Carboplatin 400 mg/m2 every 3 weeks [Level 1b]
3. Paclitaxel 170 mg/m2 for 24 hours every 3 weeks [Level 1b]
4. Topotecan 1.5 mg/m2 days 1-5 every 4 weeks [Level 1b]
COMBINATION CHEMOTHERAPY1,50,77-80
1. Cisplatin-Paclitaxel: Cisplatin 50 mg/m2 day 1, Paclitaxel 135 mg/m2 24
hours 3 weeks GOG169 77 [Level 1b]
2. Cisplatin-Topotecan: Cisplatin 50 mg/m2 day 1, Topotecan 0.75 mg/m2
days 1-3 every 3 weeks GOG179 78 [Level 1b]
3. Cisplatin-Ifosfamide: Cisplatin 50 mg/m2 day 1, Ifosfamide 5 gm/m2/24
hours every 3 weeksGOG110 [Level 1b]
4. Carboplatin-Paclitaxel: Carboplatin AUC 5-6, Paclitaxel 155-175 mg/m2
every 4 weeks81 [Level 2b]
5. Paclitaxel-Oxaliplatin: Paclitaxel 175 mg/m2 + Oxaliplatin 130 mg/m2 every
3 weeks82 [Level 2b]

d. Targeted Therapy
a. Bevacizumab 15 mg/kg IV every 21 days until disease progression83
[GRADE PRO: HIGH]
b. Pazopanib 800 mg OD and Lapatinib 1500 mg OD (Lapatinib 1000 mg
plus Pazopanib 400 mg OD or Lapatinib 1500 mg plus Pazopanib 800 mg
OD) until disease progression84 [GRADE PRO: HIGH]
c. Ongoing trial GOG 240: A randomized phase III trial of Cisplatin plus
Paclitaxel with and without NCI-supplied Bevacizumab (NSC #704865,
IND #7921) versus the Non-Platinum doublet, Topotecan plus Paclitaxel,
with and without NCI-supplied Bevacizumab, in stage IVB, recurrent or
persistent carcinoma of the cervix
FOLLOW UP
1. Weekly while on chemoradiation or 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.85
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
endocervical curettage (ECC), as warranted.86
c. Chest x-ray annually or as indicated.85
d. An annual CT scan, MRI or PET-CT scan for the first 3 years post-treatment
is recommended, or when warranted.
e. Bone scintigraphy and chest CT scan as indicated.
4. Use of a vaginal dilator 2-4 weeks after RT is suggested for women who are
sexually active.87
HORMONAL REPLACEMENT THERAPY (HRT) AFTER TREATMENT OF

CERVICAL CANCER,
Hormone therapy (HT) may be given to symptomatic women who have been treated
for cervical cancer.
1. HRT significantly reduced long term postradiation rectal, bladder and vaginal
complications.88
2. There is no evidence that HRT increases risk of squamous cell carcinoma. For
adenocarcinoma, a risk of recurrence is noted in a descriptive study.89
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ENDOMETRIAL HYPERPLASIA1,2
For premenopausal women:

HISTOLOGIC TYPE MANAGEMENT
Hyperplasia without atypia 1. (for simple hyperplasia) OCP x 6 cycles
2. MPA 10-20 mg OD x 14 days
Do ultrasound and sample endometrium after 3

months:
• IF NORMAL, MPA 5 mg x 10 days/month x 12
months
• IF PERSISTENT, increase dose 40-100 mg
daily x 3 months then do repeat biopsy.
Hyperplasia with atypia If desirous of pregnancy,
continuous MPA 20 mg OD x 3 months
Do ultrasound and sample endometrium after 3

months:
• IF NORMAL, decrease MPA 10 mg OD x 14
days for 12 more months
• IF PERSISTENT, increase MPA to 40-100 mg
daily for 3 months OR shift to Megestrol acetate
40 mg 2-4x/day (160 mg total per day) for 3
months3, then do endometrial sampling; if
persistent, do extrafascial hysterectomy (EH) ±
bilateral salpingo-oophorectomy (BSO)
If not desirous of pregnancy, do EH ± BSO

* OCP – oral contraceptive pills; MPA – medroxyprogesterone acetate
For postmenopausal women:

HISTOLOGIC TYPE MANAGEMENT
Hyperplasia without atypia • If desirous of uterine preservation, same as in
premenopausal
• If not desirous of uterine preservation, EHBSO
Hyperplasia with atypia EHBSO
Other treatment options:

1. Levonorgestrel-releasing intrauterine system (LNG-IUS)
2. Danazol 400 mg daily x 3 months
3. Gonadotrophin releasing hormone (GnRH) analogues + progestin
combination:
a. Norethisterone acetate 500 mg weekly x 3 months
b. Goserelin 3.6 mg or Leuprolin 3.75 mg depot monthly x 6 months OR
Goserelin 10.8 mg or Leuprolin 11.25 mg depot q 3 months x 6
months
Notes:
1. For women diagnosed with endometrial hyperplasia by biopsy, exclusion of a
concurrent endometrial malignancy should be done.
2. Endometrial hyperplasia is a relative contraindication to endometrial ablation. It
is paramount to exclude hyperplasia or cancer before ablating the endometrium.4

3. For women undergoing conservative management, it is recommended to
perform ultrasound and endometrial sampling after 3 months of hormonal
treatment.
4. Gynecologic Oncology Group (GOG) 167 result shows that the incidence of
invasive carcinoma in uteri in patients with preoperative diagnoses of atypical
endometrial hyperplasia (AEH) is 43%. Thus, it is recommended that for women
who will undergo EH ± BSO for AEH, sampling of peritoneal fluid for cytology
(PFC) should be performed upon opening of the peritoneal cavity. After
amputation of the cervicovaginal junction, the endometrial cavity should be
inspected. If the gross appearance of the endometrium is highly suggestive of
endometrial cancer, a bilateral pelvic lymph node dissection (BLND) ± paraaortic
lymp node sampling (PALS) should be done. If gross inspection is unequivocal,
a frozen section (FS) should be requested. The PFC specimen may be
discarded is endometrial cancer has been excluded.

ENDOMETRIAL CANCER
GENERAL GUIDELINES
1. Endometrial cancer is diagnosed by endometrial biopsy. Its accuracy in

detecting endometrial cancer is approximately 90%5
2. Dilatation and curettage or hysteroscopy is generally reserved for those

women who continue to have symptoms that cannot be explained by the
results of the office biopsy.6
The accuracy of Pipelle endometrial biopsy performed in an office is
comparable to dilatation and curettage in women with postmenopausal
bleeding with an endometrial thickness of 6 mm.7
With the 2009 International Federation of Gynecology and Obstetrics (FIGO)
staging system, performance of endocervical curettage (ECC) is no longer
necessary.8
3. Hysteroscopy may also be used for diagnosis. Based on limited studies,

office hysteroscopy does not increase the risk of transtubal fluid leakage
when performed at pressures less than 40 mmHg.9 [Level 2b]
There are also no differences in recurrence rates and/or overall survival
compared to the other diagnostic procedures.10 [Level 2b]
4. If cervical stenosis or patient tolerance does not permit an office procedure,

then curettage under anesthesia is necessary.11
5. Imaging studies can aid in the tailoring of management but not to be used as
basis for preoperative staging. The following table shows the sensitivity and
specificity of various imaging modalities in determining myometrial invasion,
cervical involvement and lymph node involvement.
IMAGING PARAMETER SENSITIVITY SPECIFICITY

MODALITY MEASURED
Ultrasound Deep myometrial 83% 72%
invasion12
Cervical involvement12 49% 72%
Lymph node 33% 100%
involvement13
CT Scan Deep myometrial 83% 42%
invasion14
Lymph node 45% 88%
involvement15
MRI Deep myometrial 92% 90%
invasion14
Lymph node 72% 97%
involvement15
*CT – computed tomography; MRI – magnetic resonance imaging
6. All patients should undergo the 2009 FIGO Surgical Staging after appropriate
investigation and clearance.8

Laparoscopy (Laparoscopic-assisted vaginal hysterectomy [LAVH] and total
laparoscopic hysterectomy [TLH]) in the following selected population
appears to be a safe procedure:16 [Level 1a]
a. endometrioid type
b. body mass index (BMI) < 60 kg/m2
c. uterine diameter < 10 cm
d. mobile uterus
e. no severe cardiopulmonary disease
f. no previous pelvic and abdominal radiation
g. with clinical stage I and II disease
h. no bulky lymph node on imaging
Laparoscopic surgery (LAVH/TLH + lymphadenectomy) has been shown to
be associated also with fewer postoperative complications, lower incidence of
transfusion, less blood loss, longer operation time but shorter hospital stay.
No difference was also seen in terms of recurrence or survival.17 [Level 1a]
Exceptions are as follows:

a. Patients who are poor surgical risk should undergo primary complete
radiotherapy with or without chemotherapy, followed by appropriate
surgery and should be classified according to the 1971 FIGO Clinical
Staging.11
b. Patients with surgically nonresectable disease should undergo primary
complete radiotherapy with or without chemotherapy, followed by
appropriate surgery and should be classified according to the 1971
FIGO Clinical Staging.11
c. Patients with a well-differentiated lesion and contraindications to
anesthesia and unsuited for radiotherapy, high-dose progestins may
be used.11
7. All specimens should be cut and examined immediately after removal to

determine the further extent of surgery.
8. Even if no longer part of the 2009 FIGO Staging System, collection of

peritoneal fluid for cytology should still be performed. Its presence should still
be indicated in the chart of the patient.8
MANAGEMENT
There is a need to identify low risk, intermediate risk, and high risk patients.18,19
Low risk:
Stage IA, grade 1 and 2, tumor diameter < 2 cm
Intermediate risk:
Stage IA, grade 1 and 2, tumor diameter > 2 cm
Stage IA, grade 3
Stage II, grade 1 and 2
Stage IB, grade 1 and 2
High risk:
Stage IB grade 3
Stage II, grade 3

Lymphadenectomy
Surgical staging for ALL endometrial cancer cases must include adequate
lymphadenectomy. Lymph node palpation is not acceptable. The decision to omit
lymph node dissection must be made together with a gynecologic oncologist. [GPP]
The definition of adequate lymphadenectomy needs further investigation. It is

suggested that the removal of 21 to 25 lymph nodes (pelvic & paraaortic) significantly
increases the probability of detecting at least 1 positive lymph node in endometrioid
uterine cancer.20 [Level 2b]
Higher stage disease (III and IV) requires less number of nodes at 11-15 to detect at
least 1 positive lymph node.
Adequate lymphadenectomy also translates to therapeutic benefit particularly for

intermediate- and high-risk patients.
Indications for aortic node sampling include:11

1. suspicious para-aortic or common iliac nodes
2. grossly positive adnexa
3. grossly positive pelvic nodes
4. high grade tumors (Grade 3)
5. clear cell or papillary serous or carcinosarcoma
6. lower uterine segment (LUS) involvement21 [Level 2b]
7. cervical involvement22 [Level 2b]
8. lymphovascular space invasion (LVSI)23
9. more than or equal to 50% myometrial invasion
STAGE I: Confined to the Corpus

SURGERY: EHBSO, PFC, Lymph Node Dissection
SURGICO-PATHOLOGIC STAGING ADJUVANT TREATMENT
IA G1, G2 No adjuvant treatment24,25 [Level 2b]
G3 Vaginal brachytherapy26,27,29
[Level 2b, GRADE PRO: HIGH)
OR
Pelvic EBRT28 [Level 1b]
IB G1,G2, G3 Vaginal brachytherapy29
[GRADE PRO: HIGH]
OR
Pelvic EBRT30 [Level 1a]
*EHBSO – extrafascial hysterectomy with bilateral salpingo-oophorectomy; PFC – peritoneal fluid cytology; EBRT
– external beam radiotherapy
Chemotherapy for early stage disease

There is conflicting evidence for the use of chemotherapy for early stage endometrial
carcinoma.31-33 [Level 1b, 2b]
EORTC 55991, a randomized trial of adjuvant treatment with sequential radiation

then chemotherapy versus radiation alone in high risk stage I endometrial carcinoma
showed 36% reduction in the risk for relapse or death (hazards ratio [HR] 0.64, 95%
confidence interval [CI] 0.41-0.99; P-0.04), thereby improving progression-free
survival in the combined modality treatment.34 [GRADE PRO: HIGH]

Notes:
1. Routine omentectomy as part of surgical staging for seemingly early stage
endometrioid type adenocarcinoma is not recommended.35 [Level 2b]
2. Adjuvant treatment for adenocarcinoma with squamous differentiation will
depend on the histological grade of the glandular component.36
3. LUS involvement is predictive of nodal spread for endometrioid histologic type
tumors (odds ratio [OR]: 5).21 [Leve; 2b]
The prognostic significance, however, remains unknown.
5. Positive LVSI regardless of stage and grade warrants adjuvant therapy since
LVSI is a strong predictor of distant and lymphatic recurrence23 and is
associated with a 2-fold risk of death.37 [Level 2b]
Adjuvant therapy is in the form of chemotherapy (Carbolatin-Paclitaxel38 [Level
1a] or Doxorubicin-based39,40 [Level 2b]) OR pelvic radiotherapy.41 [Level 1b]
6. Results of PORTEC 2 (Phase III randomized controlled trial [RCT]) study
comparing vaginal brachytherapy versus pelvic EBRT alone showed no
difference in progression-free and overall survival between the two groups but
with better quality of life for the brachytherapy group.29 [GRADE PRO: HIGH]
STAGE II: Tumor extension to the cervix confirmed by biopsy OR imaging

*For good surgical risk patients
SURGICO-PATHOLOGIC PRIMARY TREATMENT ADJUVANT
STAGING TREATMENT
II G1, G2, G3 RHBSO, PFC, Lymph Node Observe32 [Level 2b]
Dissection unless with poor surgico-
pathologic factors
[GPP]
*RHBSO – radical hysterectomy with bilateral salpingo-oophorectomy
STAGE II: Tumor extension to the cervix confirmed by biopsy OR imaging

*For poor surgical risk patients
1971 FIGO Clinical Stage II Pre-operative pelvic RT and vaginal
G1, G2, G3 brachytherapy followed by PFC and
EHBSO with lymph node evaluation11,43
[Level 4]
Notes:
1. For those patients who underwent RHBSO and whose lines of resection are
negative, brachytherapy is not necessary.44 [Level 2b]
2. Presence of any of the following poor surgico-pathologic prognostic factors after
RHBSO warrants adjuvant treatment: [GPP]
a. More than or equal to 1/3 cervical stromal invasion
b. More than or equal to 1/2 myometrial invasion
c. G3 tumors
d. Presence of LVSI

STAGE III: Tumor extension outside the uterus, within the pelvis
SURGERY: EHBSO, PFC, Lymph Node Evaluation, Debulking
SURGICO-PATHOLOGIC ADJUVANT TREATMENT
STAGING
IIIA Chemotherapy AND Pelvic EBRT
IIIB Chemotherapy AND Pelvic EBRT + vaginal
brachytherapy
IIIC1 Chemotherapy AND Pelvic EBRT+ vaginal
brachytherapy
IIIC2 Chemotherapy and EFRT + vaginal brachytherapy
*EFRT – extended field radiation therapy
Notes:
1. Current evidence does not support the use of adjuvant progestin therapy in the
primary treatment of endometrial cancer.45,46 (Level 1a, 1b)
2. Extrapelvic recurrence patterns of stage III endometrial cancer supports the use
of systemic adjuvant therapy.47 [Level 1a]
The chemotherapeutic options are as follows:
a. Carboplatin-Paclitaxel Regimen
Carboplatin (AUC of 5-7) + Paclitaxel 175 mg/m2 (3-hr infusion) every 4
weeks for 6 cycles.
The results of GOG 209 comparing Cisplatin-Doxorubin-Paclitaxel with
Filgrastim and Carboplatin-Paclitaxel for advanced stage disease have
recently been released showing no difference in terms of progression-free
and overall survival between the two groups.41
b. TAP Regimen48 [Level 1b]

Day 1: Doxorubicin 45 mg/m2 - Cisplatin 50 mg/m2
Day 2: Paclitaxel 160 mg/m2 (3-hr infusion) - Filgrastim support
Day 3 -12: Filgrastim 5 µg/kgBW SQ
Every 3 weeks for a maximum of 7 cycles or until disease progression or
unacceptable toxicity occurs. No dose reduction is required even if there is
previous RT.
Toxicities of the regimen limit its clinical use.
c. AP Regimen49 (Level 1b)

Doxorubicin 60 mg/m2 - Cisplatin 50 mg/m2 every 3 weeks for a maximum
of Doxorubicin 500 mg/m2 or until disease progression or unacceptable
toxicity occurs.
d. Cisplatin-Paclitaxel Regimen with RT32 [GRADE PRO: LOW]

D1 and 28: Cisplatin 50 mg/m2 concurrent with EBRT 4500 cGy followed
by vaginal brachytherapy then Cisplatin 50 mg/m2 - Paclitaxel 175 mg/m2
every 4 weeks for 4 courses.
e. Carboplatin (AUC 5) with Pegylated Liposomal Doxorubicin 40 mg/m2

every 4 weeks for 6 cycles50 [Level 2b]
3. The sequence of adjuvant treatment varies in the different researches as follows:

a. Adjuvant chemotherapy followed by radiation51 (Level 2b)
b. SGO-EC 9501/EORTC 55991 and MaNGO ILIADE III: Adjuvant radiation
followed by chemotherapy34 [GRADE PRO: HIGH]

c. RTOG 9708: Cisplatin 50 mg/m2 D1 and 28 with pelvic EBRT followed by 4
cycles of Cisplatin 50 mg/m2 - Paclitaxel 175 mg/m2 32 [GRADE PRO:
LOW]
d. Carboplatin 350 mg/m2 + Paclitaxel 175 mg/m2 every 3 weeks for 4 cycles
followed by involved field radiation (pelvic EBRT + extended fields + high
dose rate [HDR] brachytherapy) followed by same chemotherapy every 3
weeks for 2 cycles 52
[GRADE PRO: LOW]
4. We are awaiting results of GOG 258 and PORTEC III.
STAGE IV: Tumor invades bladder and/or bowel mucosa, + distant metastasis
SURGICO-PATHOLOGIC PRIMARY ADJUVANT TREATMENT
STAGING TREATMENT
IV G1, G2, G3 EHBSO, debulking *Chemotherapy AND EFRT
+ vaginal brachytherapy
*Chemotherapy regimens and sequence of adjuvant therapy are the same as for
stage III disease.
Notes:
1. Treatment for patients with Stage IV disease should be individualized.
2. Immediate treatment depends on the symptoms, size, site and bulk of metastatic
lesions.
POOR HISTOLOGIC TYPES:

UTERINE PAPILLARY SEROUS/CLEAR CELL CARCINOMA
SURGICO-PATHOLOGIC PRIMARY ADJUVANT TREATMENT
STAGING TREATMENT
IA with endometrial EHBSO, IO, PFC, Observation53-55 [Level 2b]
involvement only BLND, PALS, RPB
(Extended Surgical
Staging)53,54
IA with myometrial invasion EHBSO, IO, PFC, Chemotherapy** AND
and all others BLND, PALS, RPB Abdominopelvic RT54,56
(Extended Surgical [LEVEL 2b]
Staging)53,54
*IO – infracolic omentectomy, RPB – random peritoneal biopsy
54
**Chemotherapy: Carboplatin-Paclitaxel or Cisplatin-Doxorubicin
FINAL HISTOPATHOLOGY REPORT OF ENDOMETRIAL CANCER SPECIMENS

(2005 Consensus with the Philippine Society of Pathologists)
1. Histologic type
2. Histologic grade
4. Depth of myometrial invasion – divided into halves
5. Type of cervical involvement – glandular or stromal
6. Adnexal involvement
7. Parametria
8. Vaginal rim/cuff (to include distance from tumor to margin)

9. Lymph nodes – location and number
10. Peritoneal fluid
11. Tumor size (as described in the gross description of the tumor) [GPP]
PERSISTENT OR RECURRENT DISEASE11,41,48,49

Treatment for patients with persistent or recurrent disease must be individualized.
1. Treatment will depend on site, extent of disease and receptor status.
2. For localized recurrences (pelvis and para-aortic lymph nodes) or distant
metastasis in selected sites: may give irradiation.
3. Chemotherapy used for stage III/IV may be given.
4. Other chemotherapeutic agents and protocols in phase II studies which
showed favorable responses in cases of advanced or recurrent endometrial
cancer include the following with their overall response rates:
a. Carboplatin (AUC 5) with Pegylated Liposomal Doxorubicin (40
mg/m2) every 4 weeks for 6 cycles (59.5%)50 [Level 2b]
b. Liposomal doxorubicin 40 mg/m2 every 4 weeks until toxicity or
progression (36%)57 [Level 2b]
c. Weekly Paclitaxel 80 mg/m2 1 hour infusion until with response
(26.7%)58
[Level 2b]
d. Weekly Docetaxel 35 mg/m2 for 6 weeks (equivalent to 1 cycle) with a
2-week break in between cycles to complete 3 cycles (21%)59 [Level
2b]
A. ENDOMETRIAL CARCINOMA DIAGNOSED ON THE POSTOPERATIVE

HYSTERECTOMY SPECIMEN
1. For patients who underwent total hysterectomy (TH) alone:

SURGICO-PATHOLOGIC RESULT ADJUVANT TREATMENT
Ø G1, G2 2 options:
Ø < 50% myometrial invasion 1. Re-operate and remove adnexa and
Ø no LVSI perform surgical staging and give
60
Ø < 2 cm adjuvant treatment accordingly
2. No further treatment/close
observation61,62 [Level 2b]
Ø G3 Pelvic EBRT
Ø > 50% myometrial invasion
Ø > 2 cm60
Ø No LVSI
Ø No evidence of metastasis
Ø All others Re-operate to remove adnexa and
perform surgical staging and give
adjuvant treatment accordingly
2. For patients who underwent subtotal hysterectomy, re-operation to remove

the cervix and adnexa and to perform lymphadenectomy is recommended.

3. For patients who underwent total hysterectomy with bilateral salpingo-
oophorectomy (THBSO):28
SURGICO-PATHOLOGIC RESULT ADJUVANT TREATMENT
< 50% myometrial invasion G1, G2 None28 [Level 1b]
Stage IA G3 Vaginal brachytherapy29
[GRADE PRO: HIGH]
OR Pelvic EBRT28 [Level 1b]
> 50% myometrial Invasion G1, G2, G3 Vaginal brachytherapy29
Stage IB [GRADE PRO: HIGH]
OR Pelvic EBRT28 [Level 1b]
Cervical involvement G1, G2, G3 Pelvic EBRT
Stage II AND/OR Vaginal brachytherapy28,29
[Level 1b, GRADE PRO: HIGH]
PLUS chemotherapy if grade 3 tumor or
(+) LVSI
Uterine serosa and/or G1, G2, G3 Chemotherapy AND Pelvic EBRT
adnexal involvement OR EFRT and Vaginal brachytherapy
Stage III for vaginal involvement
63
Positive LVSI G1, G2, G3 Re-operate for lymphadenectomy
• If lymph node is (+), for
chemotherapy followed by EFRT
• If lymph node is (-), for pelvic
EBRT
OR
Give adjuvant therapy
4. For patients who underwent exploratory laparotomy (EL), PFC, EHBSO,

BLND + PALS
With cervical involvement G1, G2, G3 Pelvic EBRT40 [Level 1b]
AND/OR Vaginal brachytherapy29
[GRADE PRO: HIGH]
Add chemotherapy if with at least one

of the following poor prognostic factors:
[GPP]
1. > 1/3 cervical stromal invasion
2. > 1/2 myometrial invasion
3. Grade 3 tumors
4. (+) LVSI
*Imaging studies should be performed to determine extent of the disease. EFRT
should be advised if with paraaortic lymph node metastasis.
B. ENDOMETRIAL CANCER IN PATIENTS DESIROUS OF FERTILITY (LESS

THAN 40 YEARS OLD)64-67
1. If conservative treatment is contemplated, pre-treatment evaluation must be

employed
• History and physical exam
Comprehensive physical and gynecologic exam
Fertility history of both patient and spouse
Family history

• Endometrial sampling
Dilatation and curettage is preferred over endometrial biopsy since the
accuracy of the endometrial biopsy in premenopausal women is lower
and the diagnosis of endometrial carcinoma may be misinterpreted as
endometrial hyperplasia in 15-25% of cases3
• Pathology review
• Imaging with contrast-enhanced MRI68 [Level 1a]
MRI provides the highest diagnostic accuracy (85-91%) for determining
myometrial invasion. Studies using ultrasound with Doppler have
conflicting results regarding determination of myometrial invasion.69-73
[Level 2b]
In smaller scale studies, positrom emission tomography (PET) scan has
also shown usefulness in predicting myometrial invasion in endometrial
cancer.74 [Level 2b]
• Tumor marker: CA-125
• When previously performed diagnostics are inconclusive, laparoscopy
can be done to inspect the adnexae, get samples for PFC, and possible
pelvic lymph node sampling.
• Molecular markers (progestin receptors, HE4, tumor ploidy)75
2. Conservative treatment is only offered to patients who have:

• Well differentiated tumor (endometrioid type)
• No myometrial invasion
• No cervical involvement
• No adnexal involvement
• No parametrial involvement
• No vaginal involvement
• No evidence of lymph node metastasis
• Negative PFC
• No LVSI
The following are also essential:

• Progestin receptor positivity
• Careful, thorough, informed consent – Inform patients that the
procedure of preservation of fertility is still experimental and there is low
pregnancy rate.
• Patient with strong desire to preserve her childbearing potential
3. Agents used:
• Megestrol acetate 40-60 mg/day Duration of
treatment
• Medroxyprogesterone acetate (MPA) 100-800 mg/day is variable.
Other agents used:

• Tamoxifen + Progestins
• Anastrozole + Progestins
• Levonorgestrel-containing intrauterine system (LNG-IUS)
4. Monitoring
Patients are followed up with a repeat dilatation and curettage after 3
months of therapy. No response after 3 months of therapy means
treatment failure.

With reversion of the cancer, maintenance treatment with oral
contraceptive pills (OCPs), cyclic progestins, depot medroxyprogesterone
acetate (DMPA), or LNG-IUS must be given until pregnancy is desired.
If pregnancy is desired, attempts should be made after 3 months from
reversion of the cancer.
FOLLOW-UP
1. After completion of treatment, follow-up is as follows:

a. Every 3-4 months for the first 2 years, every 6 months for the next 3 years,
and yearly thereafter.
b. Pap smear should be performed at least yearly.6
c. Ideally, an annual MRI or CT scan for the first 3 years post-treatment should
be requested. Ultrasonography with or without Color Doppler studies is an
option.
d. Annual chest x-ray does not contribute to early detection of
recurrences.6,76,77 [Level 2b]
e. Bone scintigraphy and chest CT scan as indicated.
2. Particular attention has to be placed on the detection of vaginal recurrences
since isolated vaginal vault recurrences are curable in up to 87% of cases in
patients not previously exposed to radiation.77,78
3. CA-125 monitoring is recommended in cases with advanced stages (Stages III-
IV) or high risk histologic subtypes every 6 months on the first 3 years and
annually thereafter up to 5 years.76 [Level 2b]
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43. Reisinger SA, Staros EB, Field R, et al. Preoperative radiation therapy in clinical stage II endometrial
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44. Cozad SC. Stage II adenocarcinoma of the endometrium: Adjuvant radiotherapy and recurrence
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45. Martin-Hirsch PL, Lilford RJ, Jarvis GJ. Adjuvant progestagen therapy for the treatment of endometrial
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46. COSA-NZ-UK Endometrial Cancer Study Groups. Adjuvant medroxyprogesterone acetate in high risk
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endometrial cancer: A systematic review of Cochrane collaboration. Ann Oncol 2007;18:409-420.
48. Fleming G, Brunetto VL, Celia D, et al. Phase III trial of Doxorubicin plus Cisplatin with or without
Paclitaxel plus filgrastim in advanced endometrial carcinoma: A Gynecologic Oncology Group Study
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49. Thigpen JT, Brady MF, Homesley HD, et al. Phase III trial of Doxorubicin with or without Cisplatin in
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50. Pignata S, et al. A multicentre phase II study of Carboplatin plus Pegylated Liposomal Doxorubicin as
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51. Alvarez Secord A, Havrilesky LJ, Bae-Jump V, et al. The role of multimodal adjuvant chemotherapy and
radiation in women with advanced stage endometrial cancer. Gynecol Oncol 2007;107(2):285-91.
52. Lupe K, D’Souza DP, Kwon JS, et al. Adjuvant Carboplatin and Paclitaxel chemotherapy interposed with
involved field radiation for advanced endometrial cancer. Gynecol Oncol 2009;114:94-8.
53. Trope C, Kristensen GB, Abeler VM. Clear cell and papillary serous cancer: Treatment options. Best
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54. Boruta DM, Gehrig PA, Fader AN, et al. Management of women with uterine papillary serous cancer: A
Society of Gynecologic Oncology (SGO) review. Gynecol Oncol 2009;115:142-153.
55. Thomas MB, Mariani A, Cliby WA, et al. Role of systemic lymphadenopathy and adjuvant therapy in
stage I uterine papillary serous carcinoma. Gynecol Oncol 2007;107(2):186-9.
56. Steed H, Manchul L, Rosen B, et al. Uterine papillary serous carcinoma: Evaluation of multimodality
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58. Homesley HD, Meltzer NP, Nieves L, et al. A phase II trial of weekly 1-hour Paclitaxel as second-Line
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59. Gunthert AR, Ackermann S, Beckmann MW, et al. Phase II study of weekly Docetaxel in patients with
recurrent or metastatic endometrial cancer: AGO Uterus-4. Gynecol Oncol 2007;104(1):86-90.
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2003; 8:121-127.

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73. Kanat-Pektas M, Gungor T, Mollamahmutoglu L. The evaluation of endometrial tumors by transvaginal
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2006;6(1):33-41.

UTERINE SARCOMAS
GENERAL GUIDELINE
Staging will follow the 2009 International Federation of Gynecology and

Obstetrics (FIGO) surgical staging for uterine sarcoma.1
MANAGEMENT
A. Malignant Mixed Mullerian Tumor (MMMT)

STAGE Primary Treatment Adjuvant Treatment
I and II EHBSO, PFC, Pelvic EBRT4 [Level 1b]
Lymphadenectomy, IO, OR
2,3
peritoneal biopsy Cisplatin 20 mg/m2 (over 15 mins) -
[Level 2b] Ifosfamide 1.5 g/m2 (over 1 hour)5
[Level 2b]
OR
Cisplatin 75 mg/m2 - Epirubicin 75
mg/m2 (x 4-6 cycles) with pelvic
EBRT and brachytherapy in a
“sandwich” treatment6 [Level 2b]
III and IV EHBSO, PFC, Ifosfamide 1.6 g/m2 IV for 3 days +
Lymphadenectomy, IO, Paclitaxel 135 mg/m2 (3 hour
2,3
peritoneal biopsy infusion on day 1) + Filgrastim
[Level 2b] support7
[Level 1b]
Can follow this with pelvic EBRT8

(Level 2b)
Other options for chemotherapy:

1. Carboplatin AUC 5-6, Paclitaxel
175 mg/m2 for 3 hours every 4
weeks for 3-6 cycles9 [Level 2b]
2. Ifosfamide-Doxorubicin10 [Level
2b]
3. Cisplatin (60-80 mg/m2) -
Ifosfamide (1.2-1.5 mg/m2)11
[LEVEL 2b)
* EHBSO – extrafascial hysterectomy with bilateral salpingo-oophorectomy; PFC – peritoneal fluid cytology;
IO – infracolic omentectomy; RT – radiotherapy; EBRT – external beam radiotherapy;
Notes: Pelvic EBRT includes the upper half of the vagina. The use of CT-based
treatment planning and conformal blocking is considered standard of care for EBRT.
PERSISTENT/RECURRENT DISEASE
Same as for stage III/IV diseases

B. Leiomyosarcoma
I and II EH Doxorubicin 60 mg/m2 every 3
(BSO, LND not weeks (maximum of 480 mg/m2)14
mandatory)2,12,13 [Level 1b] - results favor only
[Level 2b] leiomyosarcoma but no difference
in PFS and OS
With [Level 2b] or without [Level 1a]

subsequent Pelvic EBRT and
vaginal brachytherapy15,16 [Level
2b]
III and IV EH Doxorubicin 60mg/m2 to a
(BSO, LND not maximum of 480 mg/m2 17,18 [Level
mandatory)2,12,13 1b 2b]
[Level 2b] OR
Ifosfamide plus Doxorubicin19
[Level 2b]
*LND – lymph node dissection; PFS – progression free survival; OS – overall survival
1. Gemcitabine 900 mg/m2 D1 and D8 plus Docetaxel 100 mg/m2 D8 with GCSF
D9-15 q 21 days20 [Level 2b]
2. Surgical resection for isolated sites of recurrence21 {[Level 2b]
*GCSF – granulocyst colony stimulating factor
C. Endometrial Stromal Sarcoma (ESS)

I and II EHBSO, PFC, Pelvic EBRT16,22 (LEVEL 2b)
Pelvic/Peri-aortic LN
Dissection/ If high-grade, chemotherapy with:
Assessment2,12 [Level Ifosfamide 1g - Epirubicin 25
2b] mg/m2 -Cisplatin (20 mg/m2)
OR Vincristine (1.2 mg/m2) -
Doxorubicin (20 mg/m2) -
Dacarbazine (250 mg/m2)23 [Level
4]
III and IV EHBSO, PFC, Ifosfamide 1.5 g/m2 x 5 days every
Pelvic/Peri-aortic LN 3 weeks for 6-8 courses plus
Dissection/ Mesna24 [Level 2b]
Assessment2,12 [Level Followed by pelvic EBRT16,22
2b] [Level 2b]
Notes:
a. For low-grade endometrial stromal sarcoma (ESS), hormonal therapy may be
given as adjuvant treatment (progestins, aromatase inhibitors, gonadotrophin
releasing hormone [GnRH] analogues)25,26 [Level 2b]
b. Progestins can be in the form of megestrol acetate 160 mg/day for 24 months.27
Ifosfamide 1.5 g/m2 for 5 days (reduce to 1.2 g/m2 if with previous RT) plus Mesna
every 3 weeks until unacceptable toxicity occurs24 [Level 2b]

FOLLOW-UP
After completion of treatment, recommended follow-up is as follows:

1. Every 3-4 months for the first 2 years, every 6 months for the next 3 years, and
yearly thereafter.
2. Pap smear should be performed at least yearly.
NOTE: Perform colposcopy with colpo-guided biopsy, if indicated, for abnormal
cytology results.
3. Chest x-ray every 6 months (more often if symptomatic).
4. An annual computed tomography (CT) scan, magnetic resonance imaging (MRI)
or positron emission tomography (PET)-CT scan for the first three years post-
treatment is recommended.
5. Bone scintigraphy and chest CT scan as indicated.
6. CA-125 monitoring is recommended in cases with MMMT every 6 months on the
first 3 years and annually thereafter up to 5 years.
REFERENCES
1. Tse KY, Crawford R, Ngan HYS. Staging of uterine sarcomas. Best Pract Res Clin Obstet Gynecol
25(2011): 733-49.
2. Gadducci A, Cosio S, Romanini A, et al. The management of patients with uterine sarcoma: A debated
clinical challenge. Critical Rev Oncol/Hematol 2008; 65(2):129-142.
3. Temkin SM, Hellmann M, Lee YC, et al. Early stage carcinosarcoma of the uterus: The significance of
lymph node count. Int J Gynecol Cancer 2007;17:215-219.
4. Reed N, et. al. First results of a randomized trial comparing radiotherapy versus observation
postoperatively in patients with uterine sarcomas. An EORTC-CGG Study. Int J Gynecol Cancer
2003;13(Supp 1):4.
5. Sutton G, Kauderer J, Carson LF, et al. Adjuvant Ifosfamide and Cisplatin in patients with completely
resected stage I or II carcinosarcomas (mixed mesodermal tumors) of the uterus: A Gynecologic Oncology
Group Study. Gynecol Oncol 2005; 96:630-634.
6. Manolitsas TP, Wain GV, Williams KE, et al. Mulltimodal therapy for patients with clinical stage I and II
malignant mixed mullerian tumors of the uterus. Cancer 2001;91:1437-43.
7. Homesley HD, Fillaci V, Markman M, et al. Phase III trial of Ifosfamide with or without Paclitaxel in
advanced uterine carcinosarcoma: A Gynecologic Oncology Group Study (GOG 161). J Clin Oncol
2007;25(5):526-531.
8. Clayton Smith D, Macdonald OK, Gaffney DK. The impact of adjuvant radiation therapy on survival in
women with uterine carcinosarcoma. Radiother Oncol 2007;88(2):227-32.
9. Hoskins PJ. Carboplatin plus Paclitaxel for advanced or recurrent uterine malignant mixed mullerian
tumors.The British Columbia Cancer Agency experience. Gynecol Oncol 2008;108:58-62.
10. Almeida GF, et al. Ifosfamide (IFO) and Doxorubicin (DOX) dose-intensities seem related to overall
survival in adult soft tissue sarcoma (STS) patients. J Clin Oncol 2006 ASCO Annual Meeting Proceedings
2006;24(18S):9581.
11. Menczer J, Levy T, Piura B, et al. A comparison between different postoperative treatment modalities of
uterine carcinosarcoma. Gynecol Oncol 2005;97:166-170.
12. Goff BA, Rice LW, Fleischhacker D, et al. Uterine leiomyosarcoma and endometrial stromal sarcoma:
lymph node metastases and sites of recurrence. Gynecol Oncol 1993;50:105-109.
13. Major FJ, Blessing JA, Silverberg SG, et al. Prognostic factors in early-stage uterine sarcoma. Cancer
1993;71:1902-9..
14. Omura GA, Blessing JA, Major F, et al. A randomized study of adjuvant Adriamycin in uterine sarcomas: A
Gynecologic Oncology Group Study. J Clin Oncol 1985;3:1240-1245.
15. Knocke TH, Kucera H, Dorfler D, et al Results of postoperative radiotherapy in the treatment of sarcoma of
the corpus uteri. Cancer 1998;83:1972-1979.
16. Brooks SE, Zhan M, Cote T et al. Surveillance, epidemiology and end results analysis of 2677 cases of
uterine sarcoma 1989-1999. Gynecol Oncol 2004;93:204-208.
17. Omura GA, Major FJ, Blessing JA, et al. A randomized study of Adriamycin with and without Dimethyl
Triazenoimidazole Carboxamide in advanced uterine sarcoma. Cancer 1983;52:626-632.

18. Wu TI, Chang TC, Hsueh S, et al. Prognostic factors and impact of adjuvant chemotherapy for uterine
leiomyosarcoma. Gynecol Oncol 2006;100:166-172.
19. Sutton GP, Blessing JA, Malfetano JH. Ifosfamide and Doxorubicin in the treatment of advanced
leiomyosarcomas of the uterus: A Gynecologic Oncology Group Study. Gynecol Oncol 1996;62:226-9.
20. Hensley ML, Maki E, Venkatraman E, et al. Gemcitabine and Docetaxel in patients with unresectable
leiomyosarcoma: Results of a phase II trial. J Clin Oncol 2002;20(12):2824-2831.
21. Giuntoli RL, Garrett-Mayer E, Bristow RE et al. Secondary cytoreduction in the management of recurrent
uterine leiomyosarcoma. Gynecol Oncol 2007;106(1):82-88.
22. Wietmann HD, Knocke TH, Kucera H et al. Radiation therapy in the treatment of endometrial stromal
sarcoma. Int J Radiat Oncol Biol Phys 2001;49(3):739-748.
23. Li N, Wu LY, Zhang HT, et al. Treatment options in stage I endometrial stromal sarcoma: A retrospective
analysis of 53 cases. Gynecol Oncol 2008;108(2):306-311.
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sarcomas previously unexposed to chemotherapy: A study of the Gynecologic Oncology Group. Obstet
Gynecol 1996;87:747-750.
25. Leath CA, Huh WK, Hyde J, et al. A multi-institutional review of outcomes of endometrial stromal sarcoma.
Gynecol Oncol 2007;105:630-634.
26. Reich O, Regauer S. Hormonal therapy of endometrial stromal sarcoma. Curr Opin Oncol 2007;19:347-
352.
27. Schwartz PE, et. al. Hormone Replacement Therapy and Cancer: The Current Status of Research and
Practice. Boca Raton, London, New York, Washington DC: The Parthenon Publishing Group; 2002. p.
148-54.

OVARIAN CANCER
GENERAL GUIDELINES
1. Ovarian cancer is surgically staged using the 2009 International Federation

of Gynecology and Obstetrics (FIGO) Surgical Staging Classification.1
2. There should be histologic confirmation of the disease.1
3. Pleural effusion should be aspirated for cytology.
4. Guidelines for the complete surgical staging of ovarian cancer:2

a) Systematic abdominal exploration via a midline incision
b) Sampling of washings of four areas of peritoneal cavity: diaphragm,
right and left hemi-abdomen, pelvis
c) Careful inspection and palpation of all peritoneal surfaces
d) Biopsy and resection of any suspicious lesions, masses, and
adhesions
e) Total abdominal hysterectomy + bilateral salpingo-oophorectomy
(THBSO)
f) Unilateral salpingo-oophorectomy (USO) with frozen section (FS) is
permitted in young patients with stage IA disease wanting to retain
their fertility.
g) Infracolic omentectomy (IO). For gross omental involvement, total
omentectomy or infragastric omentectomy should be performed.
h) Random biopsies of normal peritoneal surfaces, 2 samples from each
of the following: undersurface of the right hemidiaphragm, bladder
reflection, cul-de-sac, right and left paracolic recesses and pelvic
sidewalls
i) Pelvic and paraaortic lymph node sampling.
Systematic lymphadenectomy is recommended for early stage and
optimally debulked advanced ovarian cancer.3-5
j) For mucinous tumors or other types of ovarian tumors with the
appendix grossly involved with tumor, appendectomy must be
performed.2,6,7 [Level 3b]
5. Definition of optimal tumor debulking: Complete resection with zero residual

is considered optimal debulking in ovarian cancer.8
DIAGNOSTICS IN OVARIAN CANCER
1. Ultrasound remains to be the most helpful imaging examination for ovarian

cancer diagnosis with the highest sensitivity.9
Imaging Sensitivity Specificity Diagnostic

Accuracy
MRI 83% 84% 83%
Transvaginal 92% 59% 63%
ultrasound
PET/CT scan 58% 78% 76%
*MRI – magnetic resonance imaging; PET/CT – positron emission tomography / computed tomography

Features highly suggestive of ovarian cancer include: complex mass with both
solid and cystic components, papillary excrescences and projections, internal
echoes and septations, ascites and peritoneal metastasis.
Addition of Doppler studies can help in the preoperative evaluation by providing

better vascular characteristics of the ovarian masses.10
For epithelial ovarian cancer, the combination of CA-125 and human epididymal
protein 4 (HE-4) provides the highest sensitivity in predicting whether a pelvic
mass is benign or malignant.11
2. For epithelial ovarian cancer, the risk of ovarian malignancy algorithm (ROMA)
presents a predictive index with different cut-offs for premenopausal and
postmenopausal women using both CA-125 and HE-4:12
a. Premenopausal: ROMA value > 7.4% = high risk; < 7.4% = low risk
b. Postmenopausal: ROMA value > 25.3% = high risk; < 25.3% = low risk
3. The risk of malignancy index (RMI) in a woman with a pelvic mass includes a
scoring system using ultrasound, menopause status, and CA-125 serum
measurements as follows:13
RMI = U x M x CA-125
Ultrasound (U) Multiloculated cyst
Solid areas
0 = for score of 0 Positive metastasis
1 = for score of 1 Positive ascites
3 = for score of 2-5 Bilateral lesions
• Scored 1 point each
Menopause status (M) Score of 3 (menopausal)
1 = premenopausal
3 = menopausal
CA-125 Serum measurement
Cut-off is set at 200 to indicate malignancy with a sensitivity of 85% and
specificity of 97%.
SCREENING
For the average risk woman, there is no benefit of doing single or combined
screening using CA-125 and pelvic ultrasound as screening for ovarian
cancer.14

MANAGEMENT
I. EPITHELIAL OVARIAN TUMORS OF LOW MALIGNANT POTENTIAL (LMP)

(Atypically Proliferating Tumors)
STAGE STATUS INTERVENTION4,5 ADJUVANT

[Level 2b] THERAPY
Young/desirous of USO/BSO, IO, PFC, complete None
pregnancy surgical staging
IA - IB
Reproductive function not THBSO, IO, PFC, complete None
desired surgical staging
Optimally debulked THBSO, IO, PFC ± tumor Chemotherapy
(residual tumor < 2.0 cm) debulking [GPP]
IC - IV
or Sub-optimally debulked
(residual tumor ≥ 2.0 cm)
* PFC – peritoneal fluid cytology
SPECIAL CLINICAL SITUATION
Do diagnostic imaging (CT scan / MRI)

o No residual disease – surveillance
Need for adjuvant therapy will
Inadequately o (+) gross disease – OPTIONS:
depend on final surgico-pathologic
Staged Tumors 1. Re-explore and do tumor
stage
debulking (preferred option)
2. IDS
*IDS – interval debulking surgery
Notes:
1. Chemotherapy may be given if histopathology reveals invasive implants on the
peritoneal surfaces or omentum and those who develop rapid recurrence of
intraperitoneal disease, provided maximal cytoreduction was done.2,15 [Level 2b]
2. For early stage diseases, ploidy studies may be done to determine the need for
adjuvant chemotherapy. Aneuploid tumors tend to behave more aggressively16,17
II. FRANKLY MALIGNANT EPITHELIAL OVARIAN CARCINOMAS (EOC)
STAGE STATUS INTERVENTION ADJUVANT

THERAPY
IA – USO, IO, PFC, complete
Young/desirous of surgical staging
IA - IB
pregnancy IB – BSO, IO, PFC, complete
(G1, G2) None18,19 [Level 1a]
surgical staging
Reproductive function not THBSO, IO, PFC, complete
desired staging
IA - IB THBSO, IO, PFC, complete
Optimally debulked Chemotherapy*
(G3) surgical staging
THBSO, IO, PFC, complete Chemotherapy*
Sub-optimally debulked
IC - III surgical staging followed by IDS
Optimally or Sub-optimally Chemotherapy*
IV THBSO, IO, tumor debulking
debulked

Note:
For early stage diseases, ploidy studies ideally should also be done to
determine the need for adjuvant chemotherapy. Aneuploid tumors tend to
behave more aggressively.16,17
NEOADJUVANT CHEMOTHERAPY (NACT)
Neoadjuvant chemotherapy followed by IDS can be considered an option for

advanced EOCs but does not offer any advantage over primary debulking
surgery followed by chemotherapy in terms of progression-free survival (PFS)
and overall survival (OS). It offers an advantage of a higher rate of
cytoreduction and decreased morbidity.20
[GRADEPRO: LOW]
Options for Early Stages: Options for Advanced Stages:

1. Re-explore and surgically stage 1. Re-explore and do debulking
A. Inadequately
surgery, followed by 2. Chemotherapy*, followed by
Staged Tumors
chemotherapy* IDS**30,31
2. Chemotherapy*
1. Conservative surgery (USO, IO, PFC, complete surgical staging) is
standard for early stage.
B. Ovarian 2. Conservative surgery, followed by antepartal chemotherapy (Cisplatin-
Cancer in Cyclophosphamide, Cisplatin-Paclitaxel, Carboplatin-Paclitaxel use have
Pregnancy been reported)32 for advanced disease beyond second trimester
3. Completion surgery postpartum for advanced diseases or for early
stages not desirous of pregnancy
*ADJUVANT CHEMOTHERAPY IN EOC

1. The standard frontline chemotherapy is Paclitaxel 175 mg/m2 plus
Carboplatin AUC 6-7, every 21 days for 6 cycles.21 (GOG 158)
2. The combination Docetaxel 75 mg/m2 plus Carboplatin AUC 6-7, every 21

days for 6 cycles has similar response rates as Paclitaxel-Carboplatin. It is,
however, associated with more significant neutropenia.22 (SCOTROC 2004)
3. The dose-dense weekly Paclitaxel 80 mg/m2 days 1, 8, 15 in combination

with Carboplatin AUC 6 for 6-9 cycles provides a significantly longer PFS
and 3-year OS but with greater hematologic toxicity and fewer patients
completing the therapy because of toxicity.23 [GRADE PRO: MODERATE]
4. Single agent Carboplatin at AUC 5 every 3 weeks for 6 cycles can be used
as adjuvant treatment for early stage EOC.24 (ICON 1)
5. Adding a third chemotherapeutic drug (Gemcitabine, Topotecan) to

Paclitaxel and Carboplatin either as triplet or as sequential doublet
combinations does not improve PFS or OS.25 (GOG 182) [GRADE PRO:
MODERATE]

6. The administration of a component of chemotherapy via the intraperitoneal
route as part of initial management of primary EOC improves OS and
disease-free survival (DFS). Survival advantage is best seen among
women with minimal residual disease, who have not required upper
abdominal surgery, and have chemosensitive tumors. The potential for
catheter-related complications and other toxicities should be taken into
consideration.26 [GRADE PRO: MODERATE]
Regimens used for intraperitoneal chemotherapy:
a. GOG 17256
Day 1: IV Paclitaxel 135 mg/m2/24 h
Day 2: Intraperitoneal Cisplatin 100 mg/m2
Day 8: Intraperitoneal Paclitaxel 60 mg/m2
Every 21 days for 6 cycles
b. Fujiwara protocol57
Day 1 every 3 weeks
IV Paclitaxel at 175 mg/m2 diluted in 500 mL of 5% glucose administered over 3
h
Intraperitoneal Carboplatin at AUC 6, 500-1000 mL of 5% glucose is
infused through the intraperitoneal port during Paclitaxel
administration and the Carboplatin is administered as a bolus infusion
c. GOG 104/SWOG 850158

Cisplatin 100 mg/m2 intraperitoneal
Cyclophosphamide 600 mg/m2 IV
Every 21 days for 6 cycles
7. The addition of the biological agent Bevacizumab in an extended phase to

the standard Paclitaxel-Carboplatin prolongs the median PFS by about 4
months in patients with advanced EOC. Overall survival is not affected.
Most common adverse events were not significantly different save for
hypertension. [GRADE PRO: HIGH]
Dosage:
1) Paclitaxel 175 mg/m2 plus Carboplatin AUC 6 every 3 weeks for 6 cycles
plus Bevacizumab 15 mg/kg every 3 weeks from cycle 2 to 22.27 (GOG
218)
2) Paclitaxel 175 mg/m2 plus Carboplatin AUC 5-6 every 3 weeks for cycles
plus Bevacizumab 7.5 mg/kg every 3 weeks from cycle 2 to 12.28 (ICON
7)
Notes:
1. External beam radiotherapy (EBRT) for EOC is used for local palliative
management only. Whole abdominal radiotherapy (WART) as a curative
treatment may be considered as an alternative approach for patients with
intermediate risk disease, well-differentiated endometrioid cystadenocarcinoma,
pelvic residual disease ≤ 2.0 cm, abdominal residual ≤ 1.0 cm, or for patients
who are not good candidates for chemotherapy.29
2. For stage IA diseases which were completely surgically staged but with (+)
lymphovascular space invasion (LVSI), chemotherapy should be given. [GPP]

PERSISTENT OR RECURRENT DISEASE
Definitions of disease sensitivity to Platinum:33

Refractory: progression occurring while on treatment
Resistant: recurrence occurring within 0 to 6 months from treatment
Sensitive: recurrence occurring after 6 months to 24 months (or longer)
Partially sensitive: recurrence from 6 months to 12 months
Sensitive: Between 12 to 18 months
Very sensitive: recurrence occurring after 18 months
Management of rising CA-125:

Treatment for recurrence based on just a rising CA-125 (asymptomatic and no mass
on imaging) offers no survival benefit.34 [GRADE PRO: MODERATE]
Surgery for recurrent ovarian cancer:

In the presence of three factors:
1) performance status based on ECOG
2) no residual tumor after initial surgery or FIGO Stage I or II initially, and
3) less than 500 mL ascites
Surgery for recurrent disease may be considered.35 (AGO-OVAR-DESKTOP II
2009)
Regimens for tumor recurrence:

Platinum-sensitive 1) Rechallenge with Paclitaxel-Carboplatin36 (ICON 4)
and Partially 2) Carboplatin at AUC 4 D1 q 3 weeks for 6 cycles plus
platinum-sensitive Gemcitabine 1000 mg/m2 on D1 and 837 (AGO-OVAR
2.5)
3) Pegylated liposomal doxorubicin (PLD) 30 mg/m2
followed by Carboplatin AUC 5 every 4 weeks x 6
courses38 (CALYPSO)
4) Carboplatin at AUC 4 and Gemcitabine 1000 mg/m2 on
D1 and 8 for 6-10 cycles plus Bevacizumab 15 mg/kg q
3 weeks until progression39 (OCEANS)
5) PLD 30 mg/m2 90 minute infusion followed by
Trabectedin 1.1 mg/m2 3-hr infusion q 3 weeks40 (OVA-
301)
6) nanoparticle albumin-bound Paclitaxel41
Platinum 1) Topotecan weekly D1, 8, and 15 every 4 weeks42,43
refractory/resistant 2) PLD 40-50 mg/m2 every 4 week44,45
3) Gemcitabine 800-1000 mg/m2 D1 and 8 every 3 weeks
or on day 1,8,15 every 4 weeks46,47
4) Oral Etoposide 50-100 mg OD for 21 days every 28
days until progression or toxicity48
5) Weekly Paclitaxel 80 mg/m2 D1, 8, 15 every 28 days49
6) Docetaxel 75 mg/m2 plus aflibercept 6 mg/kg every 21
days50
7) Nanoparticle albumin-bound Paclitaxel 100 mg/m2 days
1, 8, 15 every 28 days51
8) Tamoxifen 20 mg BID continuous plus Goserelin 3.6 mg
SQ once a month52
9) Vinorelbine 30 mg/m2 weekly53
10) Bevacizumab 15 mg/kg every 21 days until disease
progression or prohibitive toxicity54
11) Oxaliplatin 120 mg/m2 plus PLD 40 mg/m2 over 2 days
every 21 days55

Note:
For most of the regimens, the prescribed number of courses are not written. It
generally follows that they are given until disease progression or when
prohibitive toxicity occurs.
III. GERM CELL TUMORS (GCT)
STAGE STATUS INTERVENTION ADJUVANT THERAPY

Young/desirous of USO*, IO, PFC, complete For all tumors other than
pregnancy staging pure dysgerminoma and
Reproductive function not THBSO, IO, PFC, complete low-grade (grade I)
IA, G1
desired staging immature teratoma,
chemotherapy is given59
[Level 3a]
Young/desirous of USO*, IO, PFC, complete 1. Chemotherapy**
IA, G2, G3 pregnancy staging ± tumor debulking 2. EBRT for
II – III Reproductive function not THBSO, IO, PFC, complete Dysgerminoma
desired staging ± tumor debulking
Young/desirous of USO*, IO ± tumor Chemotherapy**60
23
pregnancy debulking [Level 2b]
IV
Reproductive function not THBSO, IO ± Tumor
desired Debulking
Note: For patients whose contralateral ovary appears grossly enlarged, bisection
and FS should be done to look for foci of GCT. Wedge biopsy of a grossly normal-
looking ovary is not recommended.2
1. Re-explore and surgically stage

A. Inadequately Staged
2. Chemotherapy**
Tumors
3. Radiation therapy for dysgerminoma
standard for early stage.61
B. Ovarian Cancer in 2. Conservative surgery, followed by antepartal chemotherapy**
Pregnancy (BEP)61 for advanced disease beyond second trimester [Level 4]
3. Completion surgery postpartum for advanced diseases or for early
stages not desirous of pregnancy
**CHEMOTHERAPEUTIC REGIMENS RECOMMENDED FOR GCT

1. BEP Regimen: Bleomycin 10-30 mg/m2 D1, D8, D15 + Etoposide 100
mg/m2 + Cisplatin 20 mg/m2 every 28 days for 4 cycles2,63 [Level 2b]
Note: May opt to give EP (Etoposide + Cisplatin), if with Bleomycin toxicity.
2. VAC Regimen: Vincristine 1.5 mg/m2 every 15 days + Actinomycin 300
µg/m2 D1-5 every 28 days + Cyclophosphamide 150 mg/m2 D1-5 every 28
days for 6 cycles64
3. PVB Regimen: Cisplatin 20 mg/m2 D1-5 + Vinblastine 0.15 mg/kg D1-2 +
Bleomycin 30 mg/m2 D2, D9, D16 every 21 days for 4 cycles
4. CAP Regimen: Cisplatin 50 mg/m2 + Adriamycin 50 mg/m2 +
Cyclophophamide 500 mg/m2 every 21 days for 6 cycles
5. Vinblastine 0.11 mg/m2 + Ifosfamide 1.2 g/m2 D1-5 + Cisplatin 20 mg/m2 D1-
5 for 4 cycles

6. Ifosfamide - Doxorubicin
Chemotherapeutic Regimen for Recurrent Dysgerminoma66

Cisplatin with or without radiation therapy
Chemotherapeutic Regimens for Recurrent Non-Dysgerminoma Tumors66

1. PVB Regimen: Cisplatin + Vinblastine + Bleomycin
2. VAC Regimen: Vincristine + Actinomycin + Cyclophosphamide
3. Carboplatin-Paclitaxel
IV. SEX CORD STROMAL TUMORS (SCST)

THERAPY
Young/desirous of USO, IO, PFC, complete None [Level 1a]
IA pregnancy surgical staging
desired staging
Optimally or Sub-optimally THBSO, IO, PFC, complete 1. Chemotherapy*
IB - II debulked surgical staging (optional)
2. Pelvic EBRT
Optimally or Sub-optimally THBSO, IO ± tumor debulking 1. Chemotherapy*
III - IV
debulked 2. WART
A. Inadequately 1. Re-explore and surgically stage

Staged Tumors 2. Chemotherapy*
standard for early stage.61
2. Conservative surgery, followed by antepartal chemotherapy* for
B. Ovarian Cancer
advanced disease beyond second trimester
in Pregnancy
3. For advanced stage, completion surgery postpartum should be
performed.
4. For early stage, choice of completion surgery or close follow-up.
*CHEMOTHERAPEUTIC REGIMENS FOR SCST

1. BEP or EP Regimen: Bleomycin 10-30 mg/m2 D1, D8, D15 + Etoposide 100
mg/m2 + Cisplatin 20 mg/m2 every 28 days65 [Level 2b]
2. VAC Regimen: Vincristine 1.5 mg/m2 every 15 days + Actinomycin 300
µg/m2 D1-5 every 28 days + Cyclophosphamide 150 mg/m2 D1-5 every 28
days for 6 cycles64
3. CAP Regimen: Cisplatin 50 mg/m2 + Adriamycin 50 mg/m2 +
Cyclophophamide 500 mg/m2 every 21 days for 6 cycles
4. Carboplatin-Paclitaxel: Carboplatin AUC 5 + Paclitaxel 175 mg/m2 every 21
days for 6 cycles67,68

FINAL HISTOPATHOLOGY REPORT OF OVARIAN CANCER SPECIMENS
1. Histologic type
2. Histologic grade (especially for mucinous tumors and immature teratoma)
4. Omentum (at least 1 block per cm of its widest diameter should be sampled)
5. Biopsies, if performed (i.e. adhesions, random peritoneal biopsies, implants)
6. Lymph nodes – location and number
7. Peritoneal fluid
8. For SCST, number of mitotic figures per hpf
9. For LMP, at least 1 block per cm of tumor at its widest diameter should be
sampled
10. For mucinous tumors, differentiate between endocervical and intestinal
types
11. No mention of stage of disease in histopathologic reports
FOLLOW-UP 69
After completion of treatment, recommended follow-up is as follows:

a. Every 3 months for 4 visits, every 4 months for 3 visits, every 6 months for 6
visits, then annually thereafter
b. Determination of appropriate tumor markers every visit
c. Transvaginal ultrasound ± Color Doppler studies every 4-6 months
d. Chest x-ray if indicated by signs or symptoms (not routine)
e. An annual CT scan, MRI or PET-CT scan for the first 3 years post-treatment
is recommended, or when indicated.
f. Bone scintigraphy and chest CT scan as indicated.
g. Follow-up of patients with LMP may be at less frequent intervals.
HORMONAL REPLACEMENT THERAPY FOR OVARIAN CANCER,
1. Hormone therapy (HT) may be given to symptomatic women who have been
treated for ovarian cancer.70
2. For Endometriosis-Associated Ovarian Cancer [EAOC] (i.e. endometrioid and
clear cell carcinomas), request for estrogen-progesterone receptor (ER/PR)
assays. If ER/PR negative, HT may be given immediately for symptomatic
women. However, if ER/PR positive, HT must be deferred until after 5 years
without evidence of disease. Combined estrogen-progestin regimen is the
recommended HT.71
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FALLOPIAN TUBE CARCINOMA
GENERAL GUIDELINES
1. Fallopian tube cancer is surgically staged the 2009 International Federation

of Gynecology and Obstetrics (FIGO) Surgical Staging Classification.1
2. There should be histologic confirmation of the disease.1
3. Preoperative work-ups should include chest x-ray (CXR), abdominopelvic
computed tomography (CT) scan or magnetic resonance imaging (MRI),
tumor markers, and barium enema if indicated.
4. Pleural effusion should be aspirated for cytology.
5. Guidelines for the complete surgical staging of fallopian tube cancer:1
a) Systematic abdominal exploration via a midline incision
b) Sampling of washings of four areas of peritoneal cavity: diaphragm,
right and left hemi-abdomen, pelvis
c) Careful inspection and palpation of all peritoneal surfaces
d) Biopsy and resection of any suspicious lesions, masses, and
adhesions
e) Total abdominal hysterectomy + bilateral salpingo-oophorectomy
(THBSO)
f) Unilateral salpingo-oophorectomy (USO) with frozen section (FS) is
permitted in young patients with stage IA disease wanting to retain
their fertility.
g) Infracolic omentectomy (IO). For gross omental involvement, total
omentectomy or infragastric omentectomy should be performed.
h) Random biopsies of normal peritoneal surfaces, 2 samples from each
of the following: undersurface of the right hemidiaphragm, bladder
reflection, cul-de-sac, right and left paracolic recesses, and pelvic
sidewalls
i) Pelvic and paraaortic lymph node sampling.
j) Appendectomy may be performed.1,2,3
6. Final histopathology report of fallopian tube cancer specimens is similar to
ovarian cancer (2005 Consensus with the Philippine Society of Pathologists).
7. Follow-up post-treatment is the same as ovarian cancer.
MANAGEMENT

THERAPY
Young/desirous of USO, IO, PFC, complete surgical
IA G1 pregnancy staging1,2
None
desired staging
THBSO, IO, PFC, complete
Optimally debulked Chemotherapy*
IA G2 – surgical staging
IV Chemotherapy*
Sub-optimally debulked THBSO, IO ± tumor debulking
followed by IDS
*PFC – peritoneal fluid cytology, IDS – interval debulking surgery
*Note: Chemotherapeutic options, the timing of interval debulking surgery (IDS) (if
applicable), the management options for persistent/recurrent disease and special
clinical situations, the recommended follow-up protocol, and the reporting of the final

histopathology report of fallopian tube cancer specimens are practically the same as
those for epithelial ovarian carcinoma (EOC).

VULVAR CANCER
GENERAL GUIDELINES
1. Vulvar cancer is diagnosed by biopsy. Multiple biopsies should be taken to

include the following areas: the center of the lesion (not at its leading edge)1
and the normal surrounding skin and underlying stroma to determine stromal
invasion.2 It is preferable not to excise the entire lesion as it makes it more
difficult to plan the definitive excision.
2. An associated lesion in the vagina and the cervix must be ruled out by
careful pelvic examination with pap smear and colposcopy.2
3. If clinically indicated, proctosigmoidoscopy and cystoscopy should be done

to rule out bladder and bowel involvement.
4. A computed tomography (CT) scan or magnetic resonance imaging (MRI) of

the pelvis and groins is often helpful to detect any enlarged lymph nodes in
the groins and pelvis.3 Frozen section (FS) of clinically suspicious inguinal
nodes is recommended for advanced stage.
DEFINITION OF TERMS
a. Lateral tumor: must be 1 cm from the midline and not involving the labia
minora.
b. Superficial excision: excision of the vulvar epithelium with a 0.5-1.0 cm
margin.
c. Skinning vulvectomy: removal of the top layer of skin of the vulva (the
external female genital organs, including clitoris, vaginal lips and the
opening of the vagina). A skin graft may be used to replace the skin that was
removed.
d. Radical local excision: lateral margins of at least 1 cm, and the deep margin
should be the inferior fascia of the urogenital diaphragm, which is coplanar
with the fascia lata and the fascia over the pubic symphysis.
e. Radical vulvectomy: excision of the complete vulvar skin and subcutaneous
tissue.
f. Inguinal and femoral lymphadenectomy: removal of all lymph nodes bearing
fatty tissue between the inguinal ligament, the sartorius muscle and the
adductor longus muscle, and dissection of the femoral lymph nodes located
in the fossa ovalis medial to the femoral vein.

MANAGEMENT
I. Premalignant Lesions
International Society for the Study of Vulvovaginal Disease (ISSVD) 2004

Classifications of vulvar intraepithelial neoplasia (VIN)4,5
ISSVD 1986 Classification ISSVD 2004 Classification
VIN 1 ----
VIN 2 VIN, usual type
VIN 3 VIN, usual type
Differentiated (simplex) VIN Differentiated (simplex) VIN
*VIN 1 is poorly reproducible among pathologists and there is no evidence
that it is a precancerous lesion thus the term was discarded in 2004.
• VIN usual type is the human papillomavirus (HPV)-related type and may
have a basaloid or warty histology. It is the precursor lesion of HPV-related
invasive squamous cell carcinoma of the vulva, which is increasing in
frequency among younger women.
• Differentiated-type VIN is not related to HPV and is thought to be the

precursor lesion to the non HPV-related invasive squamous cell carcinoma
(SCCA) of the vulva observed more often in elderly women. The risk of
progression to invasion seems greater in differentiated VIN than in usual
VIN
PRE-INVASIVE PRIMARY TREATMENT ADJUVANT

TREATMENT
VIN usual and OPTIONS:6 [Level 2b] None
differentiated types 1. Superficial excision
2. Skinning vulvectomy
3. Fluorouracil cream
4. Imiquimod7,8
II. Malignant Lesions (SCCA and Bartholin’s Gland Carcinoma)
Early Disease: Disease that is limited on clinical examination to the vulva with
no evidence of nodal metastasis
Advanced Disease: Disease in which nodal metastasis is suspected and/or

where excision of the primary tumor would involve sacrifice of important midline
structures.

ALGORITHM
A. MANAGEMENT OF PRIMARY LESION
1. Early disease
2. Advanced disease

B. MANAGEMENT OF GROIN NODES
1. Clinically suspicious nodes
2. Clinically obvious nodes

MANAGEMENT BY STAGE (2009 FIGO Surgical Staging Classification)
1. Early Vulvar Cancer (Stage I) [Level 2b]
STAGE PRIMARY TREATMENT ADJUVANT

TREATMENT
Radical local excision - Complete excision Observation
Stage IA
of the lesion to allow serial sectioning and
proper assessment of depth of invasion
Radical local excision with unilateral
Stage IB Observation
inguino-femoral lymphadenectomy
Radical local excision with bilateral inguino-
femoral lymphadenectomy if:
1. Lesion within 1 cm from midline
2. Labia minora involved
3. Ipsilateral positive nodes
2. Inguinal nodes not clinically suspicious [Level 2b]

It is advisable to determine groin node status before definitive management of
primary lesion. Pre-operative CT scan/MRI may help identify extent of groin and
pelvic lymphadenopathy.
Radical vulvectomy with bilateral inguino- If with poor prognostic

Stage II
femoral lymphadenectomy factors:
*Triple incision (Hacker) technique is recommended to 1. (+) lines of resection
reduce morbidity 2. Surgical margins ≤ 8
mm
En-bloc single incision (Stanley-Way) 3. LVSI
technique recommended for:
↓
1. inguinal nodes suspicious or positive Pelvic, vulvar and
2. lesions within 1 cm of midline
bilateral inguinal
radiotherapy +
chemotherapy
*LVSI – lymphovascular space invasion
3. Inguinal nodes suspicious for metastasis [Level 2b]

If nodes are clinically suspicious for metastasis: resection of macroscopic groin
nodes followed by FS.
a. If FS POSITIVE:
- Resect any macroscopic groin and pelvic nodes seen on CT scan/MRI
and defer complete lymphadenectomy
b. If FS NEGATIVE:
Complete the inguino-femoral lymphadenectomy

Stage IIIA Tumor resectable without requiring Observation
stoma
Radical vulvectomy with bilateral inguino- If with poor prognostic
femoral lymphadenectomy factors:
1. (+) lines of resection
2. Surgical margins ≤ 8
mm
3. LVSI
Pelvic, vulvar and

bilateral inguinal
radiotherapy
Tumor resection would require stoma
Primary radiation (pelvic, vulvar and
bilateral inguinal radiotherapy) +
chemotherapy followed by consideration of
surgical resection.
Stage IIIB, Tumor resectable without requiring Pelvic and bilateral
IIIC stoma inguinal radiotherapy
Radical vulvectomy with bilateral inguino-
femoral lymphadenectomy
Tumor resection would require stoma
Pre-operative radiotherapy (pelvic,vulvar
and bilateral inguinal radiotherapy) +
chemotherapy followed by consideration of
surgical resection.
4. Advanced Stage Vulvar Cancer (Stage IV)
Stage IVA, Primary radiation (pelvic, vulvar & bilateral

IVB inguinal radiotherapy) + chemotherapy
followed by consideration of surgical
resection.
Concurrent Chemotherapy:
1. Cisplatin (GOG Protocol 205)58 [GRADE PRO: LOW]
• Cisplatin 40 mg/m2 weekly
2. Cisplatin + 5-FU protocol (GOG Protocol 101)31
• Cisplatin (50 mg/m2) on D1 and 21 of radiation therapy
• 5-FU (1000 mg/m2) per 24h continuous IV infusion over 96h on D2-5 and
D22-25 of radiation therapy
3. 5-FU + Mitomycin C protocol
• 5-FU (1000 mg/m2) per 24h continuous IV infusion over 96h on D1-4 and
D21-24 of radiation therapy
• Mitomycin C (10 mg/m2) on D1 and 21 of radiation therapy

TUMOR PERSISTENCE/RECURRENCE
Local vulvar Options: [Level 3b]
recurrence No previous RT:
1. Chemoradiation (vulvar and inguinal EBRT +
chemotherapy)
2. Wide local excision with or without
chemoradiation/radiation in patients with small volume
recurrent tumor
Previously irradiated:
1. Wide local excision in patients with small volume
recurrent tumor
2. Radical exenterative surgery
3. Chemotherapy [GRADE PRO: LOW]
a. Cisplatin 80 mg/m2 D1 and Vinorelbine 25 mg/m2
D1-860
b. Paclitaxel 175 mg/m2 every 3 weeks61
c. Cisplatin 50 mg/m2 D1, 5-FU 1000 mg/m2 D1-460
Groin node recurrence Options: [Level 3b]
1. If no previous surgery has been done, radical
vulvectomy, BGND or pelvic exenteration
2. If previous surgery without adjuvant radiation had
been done, resect affected nodes (if possible to
optimize the response to radiation) followed by
radiation therapy
*EBRT – external beam radiotherapy; BGND – bilateral groin node dissection
FINAL HISTOPATHOLOGY REPORT OF VULVAR CANCER SPECIMENS

1. Histologic type
2. Histologic grade
3. Lymphovascular space invasion (LVSI)
4. Margins (lateral and posterior margins) – to include distance from tumor to
margin
5. Lymph nodes – location, number, size (microscopic or macroscopic
involvement), extracapsular spread
6. For microinvasive tumor on biopsy, state depth of invasion in millimeter (mm)
FOLLOW-UP
1. Weekly while on radiotherapy

2. Two weeks post-brachytherapy
a. Every three months for the 1st 2 years, every 6 months for the next 3 years,
then yearly thereafter.
b. Pap smear every 6 months for the 1st 2 years, followed by annual Pap
smear thereafter.
NOTE: Perform colposcopy with colposcopy-guided biopsy, if indicated, for
abnormal cytology results.
4. Ideally, an annual CT scan/MRI for the first three years post treatment should be
requested.
5. Chest x-ray every 6 months for the first 2 years then yearly thereafter.
6. Bone scintigraphy and chest CT scan as indicated

VULVAR MELANOMA
CLARK’S PRIMARY TREATMENT ADJUVANT

LEVEL
1. For tumor < 1 mm thick: 1. Alpha interferon
I-V
- Wide local excision 2. Immunotherapy (Dendritic
with at least 1 cm immunotherapy)
surgical margin 3. Interleukin-2
4. Chemotherapy
2. For intermediate Options:
thickness melanoma (1-4 a. Dacarbazine (DTIC) – standard
mm): chemotherapy single dose of
- Wide local excision 800 mg/m2 every 3 weeks
with at least 2 cm b. DTIC + Interferon alpha – DTIC
surgical margins 800 mg/m2 every 3 weeks +
Interferon alpha 9 mlU 3x/week
3. Regardless of the c. Dartmouth Regimen – DTIC 220
thickness, in all cases it is mg/m2 on days 1-3 + Carmustine
necessary to include at 150 mg/m2 every other cycle +
least a 1 cm deep margin Cisplatin 25 mg/m2 days 1-3 +
extending through the Tamoxifen 40 mg days every 3
subcutaneous fat to the weeks
muscular fascia below d. Temozolomide
[Level 3b] - Untreated: 200 mg/m2/day x 5
days every 28 days
4. Lymph node dissection - Received prior chemotherapy:
for patients > 60 years, 150 mg/m2/day x 5 days
tumor thickness of 1-2 every 28 days
mm and without tumor
ulceration. [Level 2b]
PAGET’S DISEASE OF THE VULVA
GENERAL GUIDELINE
Up to 10-15% of cases of vulvar Paget’s disease are associated with an

underlying adenocarcinoma. Furthermore, many patients diagnosed with Paget’s
disease are ultimately diagnosed with associated malignancies at non-vulvar
sites such as adenocarcinoma of the breast, stomach, bladder or other sites.
Therefore, it is important not only to obtain adequate margins adjacent to and
beneath the diseased skin, but also to search for both an underlying carcinoma
as well as carcinoma at other unrelated sites.
TREATMENT
• Wide local excision with removal of underlying dermis, in the absence of clinical
or histologic evidence of invasive carcinoma. [Level 3b]
• Removal of a small amount of subcutaneous tissue to rule out an underlying
occult adenocarcinoma.
• FS of surgical margins is recommended to ensure complete removal of tumor
and adequate, disease-free margins. [Level 3b]

Options:
1. Take multiple representative samples around the specimen and send for FS.
2. Extend surgical margins beyond the usual margins of the gross lesion.
3. If no FS, wait for final histopathology report of specimen and do re-excision if
necessary.
4. Wait for recurrence to develop the re-excise, (the disease is slow-growing and is
amenable to excision).
• Lymphadenectomy is not required unless an underlying adenocarcinoma is

detected, for which modified radical or radical vulvectomy is necessary to
eradicate the disease.
Other Options:
1. Wide local excision with at least 1-2 cm margin
2. Imiquimod
3. CO2, laser vaporization
BASAL CELL CARCINOMA OF THE VULVA
TREATMENT
Wide local excision with least 1 cm margin. [Level 3b]
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6. Woodruff JD, Julian C, Puray T, et al. The contemporary challenge of carcinoma of the vulva. Am J
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7. Lavazzo C, Pitsouni E, Athanasiou S, et al. Imiquimod for treatment of vulvar and vaginal intraepithelial
neoplasia, Int J Gynecol Obstet 2008;10(1):3-10.
8. Le T. Menard C, Hicks-Boucher W, et al. Final results of a phase 2 study using continuous 5%
Imiquimod cream application in the primary treatment of high-grade vulva intraepithelial neoplasia.
Gynecol Oncol 2007;106:579-584.
9. Hacker NF, Van der Velden J. Conservative management of early vulvar cancer. Cancer 1993;71(4
Suppl):1673-1677.
10. Iverson T, Abeler V, Aalders J. Individualized treatment of stage I carcinoma of the vulva. Obstet
Gynecol 1981;57:85-90.
11. Hacker NF, Berek JS, Lagasse LD, et al. Individualization of treatment for stage I squamous cell vulvar
carcinoma. Obstet Gynecol 1984;63:155-162.
12. Farias-Eisner R, Cirisano FD, Grouse D, et al. Conservative and individualized surgery for early
squamous carcinoma of the vulva: treatment of choice for stage I and II (T1-2NO-1MO) disease.
Gynecol Oncol1994;53:55-58.
13. Burke TW, Levenback C, Coleman RL, et al. Surgical therapy of T1 and T2 vulvar carcinoma: further
experience with radical wide excision and selective inguinal lymphadenectomy. Gynecol Oncol
1995;57:215-220.

14. Malfetano JH, Piver MS, Tsukada Y, et al. Univariate and multivariate analyses of 5-year survival,
recurrence, and inguinal node metastases in stage I and II vulvar carcinoma. J Surg Oncol
1985;30(2):124-131.
15. Stehman FB, Bundy BN, Dvoretsky PM, et al. Early stage I carcinoma of the vulva treated with ipsilateral
superficial inguinal lymphadenectomy and modified radical hemivulvectomy: a prospective study of the
Gynecologic Oncology Group. Obstet Gynecol 1992;79(4):490-497.
16. Hacker NF, Van der Velden J. Conservative management of early vulvar cancer. Cancer 1993;71(4
Suppl):1673-1677.
17. Ansink A, van der Velden J, Collingwood M. Surgical interventions for early squamous cell carcinoma of
the vulva. Cochrane Database Syst Rev1999, Issue 4, Art. No. : CD002036
18. Hoffman MS, Roberts WS, LaPolla JP, et al. Recent modifications in the treatment of invasive squamous
cell carcinoma of the vulva. Obstet Gynecol Surv 1989;44(4):227-233.
19. Petereit DG, Mehta MP, Buchler DA, et al. Inguinofemoral radiation of N0, N1 vulvar cancer may be
equivalent to lymphadenectomy if proper radiation technique is used. Int J Radiat Oncol Biol Phys
1993;27(4):963-967.
20. Slevin NJ, Pointon RC. Radical radiotherapy for carcinoma of the vulva. Br J Radiol 1989;62(734):145-
147.
21. Perez CA, Grigsby PW, Galakatos A, et al. Radiation therapy in management of carcinoma of the vulva
with emphasis on conservation therapy. Cancer 1993;71(11):3707-3716.
22. Heaps J, Fu YS, Montz F, et al. Surgical-pathologic variables predictive of local recurrence in squamous
cell carcinoma of the vulva. Gynecol Oncol 1990;38:309-314.
23. Hacker N. Radical resection of vulvar malignancies : a paradigm shift in surgical approaches. Curr Opin
Obstet Gynecol 1999;11:61-64.
24. Origoni M, Sideri M, Garcia S, et al. Prognostic value of pathological patterns of lymph node positivity in
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25. Kumar PP, Good RR, Scott JC. Techniques for management of vulvar cancer by irradiation alone.
Radiat Med 1988; 6(4):185-191.
26. Thomas GM, Dembo AJ, Bryson SC, et al. Changing concepts in the management of vulvar cancer.
Gynecol Oncol 1991;42(1):9-21.
27. Faul CM, Mirmow D, Huang Q, et al. Adjuvant radiation for vulvar carcinoma: improved local control. Int
J Radiat Oncol Biol Phys1997;38(2):381-389.
28. Homesley HD, Bundy BN, Sedlis A, et al. Prognostic factors for groin node metastasis in squamous cell
carcinoma of the vulva (a Gynecologic Oncology Group study). Gynecol Oncol 1993;49(3):279-283.
29. Boronow RC, Hickman BT, Reagan MT, et al. Combined therapy as an alternative to exenteration for
locally advanced vulvovaginal cancer: II. Results, complications, and dosimetric and surgical
considerations. Am J Clin Oncol 1987; 10(2):171-181.
30. Anderson JM, Cassady JR, Shimm DS, et al. Vulvar carcinoma. Int J Radiat Oncol Biol Phys
1995;32(5):1351-1357.
31. Montana GS, Thomas GM, Moore DH, et al. Preoperative chemoradiation for carcinoma of the vulva
with N2/N3 nodes: a Gynecologic Oncology Group study. Int J Radiat Oncol Biol Phys 2000;48(4):1007-
13.
32. Han SC, Kim DH, Higgins SA, et al. Chemoradiation as primary or adjuvant treatment for locally
advanced carcinoma of the vulva. Int J Radiat Oncol Biol Phys 2000;47(5):1235-44.
33. Landoni F, Maneo A, Zanetta G, et al. Concurrent preoperative chemotherapy with 5-Fluorouracil and
Mitomycin C and radiotherapy (FUMIR) followed by limited surgery in locally advanced and recurrent
vulvar carcinoma. Gynecol Oncol 1996;61:321-27.
34. Eifel PJ, Morris M, Burke TW, et al. Prolonged continuous infusion Cisplatin and 5-Fluorouracil with
radiation for locally advanced carcinoma of the vulva. Gynecol Oncol 1995;59:51-56.
35. Cunningham MJ, Goyer RP, Gibbons SK, et al. Primary radiation, Cisplatin and 5-Fluorouracil for
advanced squamous carcinoma of the vulva. Gynecol Oncol 1997;66:258-261.
36. Moore HD, Thomas GM, Montana GS, et al. Preoperative chemoradiation for advanced vulvar cancer: A
phase II study of the Gynecologic Oncology Group. Int J Radiat Oncol Biol Phys 1998;42(1):79-85.
37. Arvas M, Kose F, Gezer A, et al. Radical versus conservative surgery for vulvar carcinoma. Int J
Gynecol Obstet 2005; 88(2):127-133.
38. Hruby G, Macleod C, Firth I. Radiation treatment in recurrent squamous cell cancer of the vulva. Int J
Radiat Oncol Biol Phys 2000;46(5):1193-1197.
39. Couter J. Local and regional recurrence of vulvar cancer : management dilemmas. Best Pract Res Clin
Obstet Gynaecol 2003;17(4):663-681.
40. Russell AH, Mesic JB, Scudder SA, et al. Synchronous radiation and cytotoxic chemotherapy for locally
advanced or recurrent squamous cancer of the vulva. Gynecol Oncol 1992;47(1):14-20.

41. Berek JS, Heaps JM, Fu YS, et al. Concurrent Cisplatin and 5-Fluorouracil chemotherapy and radiation
therapy for advanced-stage squamous carcinoma of the vulva. Gynecol Oncol 1991;42(3):197-201.
42. Koh WJ, Wallace HJ, Greer BE, et al. Combined radiotherapy and chemotherapy in the management of
localregionally advanced vulvar cancer. Int J Radiat Oncol Biol Phys 1993;26(5):809-816.
43. Trimble EL, Lewis JL Jr, Williams LL, et al. Management of vulvar melanoma. Gynecol Oncol
1992;45:254-258.
44. Verschraegen CF, Benjapibal M, Supakarapongkul W, et al. Vulvar melanoma at the M.D. Anderson
Cancer Center: 25 years later. Int J Gynecol Cancer 2001;11: 359-364.
45. Irvin WP Jr, Legallo RL, Stoler MH, et al. Vulvar melanoma: a retrospective analysis andliterature
review. Gynecol Oncol 2001;83:457-465.
46. Rodriguez AO. Female genital tract melanoma: the evidence is only skin deep. Curr Opin Obstet
Gynecol 2005;17:1-4.
47. Paul MJ, Summers Y, Calvert AH, et al. Effect of temozolomide on central nervous system relapse in
patients with advanced melaloma. Melanoma Res 2002;12:175-178.
48. Middleton MR, Grob JJ, Aaronson N, et al. Randomized phase II trial of Temozolomide versus
Dacarabazine in the treatment of patients with advanced metastatic malignant melanoma. J Clin Oncol
2000;18:158-166.
49. Louis-Sylvestre C, Haddad B, Paniel BJ. Paget’s disease of the vulva: results of different conservative
treatments. Eur J Obstet Gynecol Reprod Biol 2001;99:253-255.
50. Preti M, Micheletti L, Massobrio M, et al. Vulvar Paget’s disease: one century after first reported. J Lower
Gen Tract Dis 2003;7(2):122-135.
51. De Hullu J, Van der Zee. Surgery and radiotherapy in vulvar cancer. Crit Rev Oncol Hematol
2006;60:38-58.
52. Copeland L, Sneige N, Gershensen DM, et al. Bartholin gland carcinoma. Obstet Gynecol 1986;67:764-
801.
53. Feakings RM, Lowe DG. Basal cell carcinoma of the vulva: a clinicopathologic study of 45 cases. Int J
Gynecol Path 1997;16(4):319-24.
54. Pisani C, Poggiali S, De Padova L, et al. Basal cell carcinoma of the vulva. J Eur Acad Dermatol
Venereol 2006;20(4):446-8.
55. Benedet JL, Miller DM, Ehlen TG, et al. Basal cell carcinoma: clinical features and treatment results in
28 patients. Obstet Gynecol 1997;90(5):765-8.
56. Lopez-Varela E, Olivay E, Mcintyrez JF et al. Primary treatment of Bartholin’s gland carcinoma with
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57. Finan MA, Barre G. Bartholin’s gland carcinoma, malignant melanoma and other rare tumours of the
vulva. Best Pract Res Clin Obstet Gynaecol 2003;17(4):609–633.
58. Moore DH, Ali S, Koh WJ, et al. A phase II trial of radiation therapy and weekly cisplatin chemotherapy
for the treatment of locally-advanced squamous cell carcinoma of the vulva: A Gynecologic Oncology
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59. Mak RH, Halasz LM, Tanaka CK, et al. Outcomes after radiation therapy with concurrent weekly
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carcinoma of the vulva. Gynecol Oncol 2011;120:101-107.
60. Tomao F, DiTucci C, Marchetti C, et al. Role of chemotherapy in themanagement of vulvar carcinoma.
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61. Witteveen PO, van der Velden J, Vergote I, et al. Phase II study on Paclitaxel in patients with recurrent,
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EORTC-GCG (European Organisation for Research andTreatment of Cancer-Gynaecological Cancer
Group). Ann Oncol Advance Access, 2009:1-6.

VAGINAL CANCER
GENERAL GUIDELINES
1. Vaginal cancer is diagnosed by biopsy and clinically staged using the 2009
FIGO Staging Classification.1
2. Due to proximity to other organs, diagnostic examinations to rule out
adjuvant organ (particularly, cervix and vulva) primaries should be done.1
3. Colposcopy, cystoscopy, and proctosigmoidoscopy should be performed, if
clinically indicated.
4. A complete systematic evaluation for patients with malignant melanoma and
advanced stage vaginal cancer should be performed.
5. Radiation therapy is the treatment of choice for most patients with vaginal
cancer, and comprises an integration of teletherapy and
intracavitary/interstitial therapy.1
MANAGEMENT
I. Premalignant Lesions
PRE-INVASIVE TREATMENT
1,5,6,10
VAIN I-III OPTIONS: [Level 3b]
1. Wide local excision (excisional procedures either with
electrosurgical loops or scalpel incision)1
2. Brachytherapy.1,8
3. For multifocal/extensive disease, partial or total vaginectomy
with or without skin grafting10
4. 5-FU cream1,6
5. 5% Imiquimod cream13
II. Malignant Disease
STAGE TREATMENT OPTIONS

STAGE SIZE TREATMENT OPTIONS ADJUVANT THERAPY
I < 0.5 cm Options: [Level 2b] For those who underwent
thick 1. Wide local excision or primary surgery, if with < 1
total vaginectomy with cm or positive surgical
vagina reconstruction3 margin:
2. Brachytherapy2 • Interstitial or vaginal
3. Complete RT with brachytherapy
inguinal boost2
> 0.5 cm 1. Interstitial or For those who underwent
thick intracavitary primary surgery, if with <
radiotherapy with 1cm or positive surgical
EBRT2,16 margin:
2. RH with pelvic • Interstitial or vaginal
lymphadenectomy for brachytherapy
lesions of the upper
posterior third of the
vagina1,5,10

3. For lesions of the lower
third of the vagina:
a. Complete RT +
inguinal boost
b. Radical vaginectomy
with inguinal
lymphadenectomy +
partial resection of
the vulva2
For poorly differentiated
tumors:
Complete RT + inguinal
EBRT2,16
II 1. For small lesions (< 5 cm), interstitial or intracavitary brachytherapy
For larger lesions, pelvic EBRT followed by interstitial or
intracavitary brachytherapy1,14
2. Concurrent chemoradiation with Cisplatin15 [Level 3b]
3. Chemoradiation with 5-FU with or without Cisplatin or Mitomycin4
4. Radical surgery (radical vaginectomy or pelvic exenteration) with or
without RT3,10,11
III-IVA 1. Radiotherapy:
- EBRT + interstitial and/or intracavitary brachytherapy2
2. Concurrent chemoradiation with Cisplatin15 [Level 3b]
3. Chemoradiation with 5-FU with or without Cisplatin or Mitomycin
plus additional dose to the lateral pelvic wall4
4. Pelvic exenteration with pelvic lymphadenectomy or pre-operative
radiation1
5. For lesions involving the lower third of the vagina, pelvic
exenteration with pelvic lymphadenectomy and bilateral groin node
dissection1
IVB 1. Chemoradiotherapy with 5-FU with or without Cisplatin or
Persistent/ Mitomycin plus additional dose to the lateral pelvic wall4
Recurrent 2. Pelvic exenteration1
*RT – radiotherapy; EBRT – external beam radiotherapy; RH – radical hysterectomy;
FINAL HISTOPATHOLOGY REPORT OF VAGINAL CANCER SPECIMENS

1. Histologic type
2. Histologic grade
3. Lymphovascular space invasion (LVSI)
4. If surgical treatment is performed, state status of margins.
5. If radical hysterectomy (RH) performed, follow same recommendations for
final histopathology report for cervical cancer.
FOLLOW-UP
1. Weekly while on radiotherapy.

2. Two weeks post-brachytherapy.
a. Every three months for the 1st 2 years, every 6 months for the next 3 years,
then yearly thereafter.

b. Pap smear every 6 months for the 1st two year, followed by annual Pap
smear thereafter.
NOTE: Perform colposcopy with colpo-guided biopsy, if indicated, for
abnormal cytology results.
4. Ideally, an annual computed tomography (CT) scan or magnetic resonance
imaging (MRI) for the first three years post-treatment should be requested.
5. Annual chest x-ray
6. Bone scintigraphy and chest CT scan as indicated
VAGINAL MELANOMA
CLARK’S TREATMENT
LEVEL
I-V 1. Wide local excision17,18
2. Radiation therapy using high-dose fractions19
3. Pelvic exenteration
REFERENCES
1. Benedet JL, Pecorelli S, Ngan HYS, et al. Cancer of the vagina. Staging classifications and clinical
practice guidelines of gynecologic cancers by FIGO Committee on Oncology and IGCS Guidelines
Committee, 3rd edition:26-35. November 2006.
2. Urbanski K, Kojs Z, Reinfuss M, et al. Primary invasive vaginal carcinoma treated with radiotherapy:
Analysis of prognostic factors. Gynecol Oncol 1996;60:16-20.
3. Tjalma W, Monaghan J, Lopes A, et al. The role of surgery in invasive squamous carcinoma of the
vagina. Gynecol Oncol 2001;81:360-365.
4. Dalrymple J, Russell A, Lee S, et al. Chemoradiation for primary invasive squamous carcinoma of the
vagina. Int J Gynecol Oncol 2004;14:110-117.
5. Creasman W. Vaginal cancers. Curr Opin Obstet Gynecol 2005;17:71-76.
6. Krebs HB. Treatment of vaginal intraepithelial neoplasia with laser and topical 5-Fluorouracil. Obstet
Gynecol 1989; 73(4):657-660.
7. Perez CA, Camel HM, Galakatos AE, et al. Definitive irradiation in carcinoma of the vagina: long-term
evaluation of results. Int J Radiat Oncol Biol Phys 1988;15(6):1283-1290.
8. Woodman CB, Mould JJ, Jordan JA. Radiotherapy in the management of vaginal intraepithelial
neoplasia after hysterectomy. Br J Obstet Gynaecol 1988;95(10):976-979.
9. Perez CA, Madoc-Jones H. Carcinoma of the vagina. In: Perez CA, Brady LW (Eds) Principles and
Practice of Radiation Oncology. Philadelphia: JB Lippincott, 1987;1023-1035.
10. Stock RG, Chen AS, Seski J. A 30-year experience in the management of primary carcinoma of the
vagina: analysis of prognostic factors and treatment modalities. Gynecol Oncol 1995;56(1):45-52.
11. Rubin SC, Young J, Mikuta JJ. Squamous carcinoma of the vagina: treatment, complications, and long-
term follow-up. Gynecol Oncol 1985;20:346-353.
12. Boronow RC, Hickman BT, Reagan MT, et al. Combined therapy as an alternative to exenteration for
locally advanced vulvovaginal cancer: II. Results, complications, and dosimetric and surgical
considerations. Am J Clin Oncol 1987;5(2): 171-181.
13. Le T, Menard C, Hicks-Boucher W, et al. Final results of a phase 2 study using continuous 5%
Imiquimod cream application in the primary treatment of high grade vulva intraepithelial neoplasia.
Gynecol Oncol 2007;106:579-584.
14. Chyle V, Zagars G, Wheeler J. Definitive radiotherapy for carcinoma of the vagina: Outcome and
prognostic factors. Int J Radiat Oncol Biol Phys 1996;35(5):891-905.
15. Samant R, Lau B, Choan E, et al. Primary vaginal cancer treated with concurrent chemoradiation using
Cisplatinum. Int J Radiat Oncol Biol Phys 2007;69(3):746-750.
16. Perez CA, Grigsby PW, Garipagaoglu M. Factors affecting long-term outcome of irradiation in carcinoma
of the vagina. Int J Radiat Oncol Biol Physiol 1999;44(1):37-45.
17. Reid GC, Schmidt RW, Roberts JA, et al. Primary melanoma of the vagina: a clinico-pathologic analysis.
Obstet Gynecol 1989;74:190-199.

18. Buchanan DJ, Schlaerth J, Kurosaki T. Primary vaginal melanoma: Thirteen year disease-free survival
after wide local excision and recent literature review. Am J Obstet Gynecol 1998;178:912-917.
19. Harwood AR, Cumming BJ. Radiotherapy for mucosal melanoma. Int J Radiat Oncol Biol Physiol
1982;8:1121-1127.

PREVENTION AND TREATMENT OF COMPLICATIONS
I. GUIDELINES FOR THE USE OF ANTIEMETICS
DEFINITION
ACUTE EMESIS – Initial 24o after chemotherapy

DELAYED EMESIS – Later than 24o after chemotherapy
ANTICIPATORY EMESIS – Days to hours before chemotherapy
BREAKTHROUGH EMESIS – Occurs despite prophylactic treatment and/or
requires rescue with antiemetic agents1
REFRACTORY EMESIS – Occurs during subsequent treatment cycles when
antiemetic prophylaxis and/or rescue have failed in earlier cycles1
GENERAL PRINCIPLES1
1. The goal of emesis control is prevention.

2. When present, know the cause of emesis. In the presence of identifiable cause,
specific treatment should be given.
OTHER CAUSES OF NAUSEA AND VOMITING TO BE CONSIDERED

1. Infection 7. Metastases (brain, liver, bone)
2. Metabolic disorders 8. Paraneoplastic
3. Electrolyte disturbances 9. Other emetogenic drugs
4. Constipation (opioids, antibiotics, antifungals)
5. Gastrointestinal obstruction 10. Psychologic
6. Cachexia syndrome
3. In addition to antiemetic use, patients should be advised to adjust their eating

habits: small frequent meals, full liquid diet, food at room temperature.
CHEMOTHERAPY-INDUCED EMESIS
DAY 1 DAYS 2-3

HIGH EMETIC RISK (>90%)
Three-drug combination antiemetic: 5-HT3 serotonin receptor antagonist +
dexamethasone + NK1 receptor antagonist2 [Level 1a]
Carmustine 5-HT3 serotonin
Cisplatin > 50 mg/m2 receptor antagonists:
Cyclophosphamide > 1,500 Granisetron 2 mg PO
mg/m2 or 1 mg IV (0.01
Dacarbazine mg/kg) or 3.1 mg/24
Dactinomycin hrs transdermal
Doxorubicin > 60 mg/m2 patch1
Epirubicin < 90 mg/m2 Ondansetron 24 mg
Ifosfamide > 10 g/m2 PO or 8 mg IV (0.15
mg/kg)
Tropisetron 5 mg
PO/IV
Ramosetron 300 µg
IV3

Palonosetron 0.25 mg
IV1*
+ Dexamethasone 12 Dexamethasone 8 mg
mg PO/IV PO
+ NK1 antagonists: + NK1 antagonists:
Aprepitant 125 mg PO Aprepitant 80 mg PO
*Among the different antiemetics, palosetron is preferred over the other antiemetics as it has
4,5
been shown to be associated with prolonged inhibition of the 5-HT3 receptor , however, this
drug is not locally available.
MODERATE EMETIC RISK (30-90%)

Two-drug combination antiemetic: 5-HT3 serotonin receptor antagonist +
dexamethasone [Level 2a]
Carboplatin 5-HT3 serotonin 5-HT3 serotonin
Cisplatin < 50 mg/m2 receptor antagonists: receptor antagonists
Cyclophosphamide < 1,500 Granisetron 2 mg PO
mg/m2 or 1 mg IV (0.01
Doxorubicin < 60 mg/m2 mg/kg) or 3.1 mg/24
Epirubicin < 90 mg/m2 hrs transdermal
Etoposide (oral) patch1
2
Ifosfamide < 10 mg/m Ondansetron 16-24
Interferon alpha > 10 mIU/m2 mg PO or 8 mg IV
Irinotecan (0.15 mg/kg)
Melphalan Tropisetron 5 mg
Oxaliplatin PO/IV
Temozolomide Ramosetron 300 µg
Vinorelbine IV3
Palonosetron 0.25 mg
IV1*
+ Dexamethasone 8-12 OR Dexamethasone 8
mg PO/IV1 mg PO
*There is limited evidence on the addition of aprepitant, but should be considered when giving
1,3,6
carboplatin, cisplatin, doxorubicin, epirubicin, ifosfamide, irinotecan or methotrexate.
LOW EMETIC RISK (10-30%)

Single drug antiemetic: dexamethasone [Level 2a]
Capecitabine Dexamethasone 8 mg
Docetaxel PO
Etoposide (IV)
Fluorouracil
Gemcitabine
Interferon alpha < 10 mIU/m2
Liposomal doxorubicin
Methotrexate (IV)
Mitomycin
Paclitaxel

MINIMAL EMETIC RISK (<10%)
Bevacizumab No antiemetic is
Bleomycin routinely administered
Methotrexate (oral) (Level II, Grade A)
Interferon alpha < 5 mIU/m2
Vinblastine
Vincristine
Vinorelbine
SPECIAL EMETIC PROBLEMS
COMBINATION Administer antiemetics appropriate for the

CHEMOTHERAPY component chemotherapeutic agent of greatest
emetic risk
MULTIPLE CONSECUTIVE Administer antiemetics appropriate for the risk
DAYS OF CHEMOTHERAPY class of the chemotherapy for each day of the
chemotherapy
ANTICIPATORY EMESIS PREVENTION: Use most active antiemetic
regimens appropriate for the chemotherapy being
administered to prevent acute or delayed emesis
TREATMENT:1
1. Behavioral therapy (e.g. systematic
desensitization, relaxation, hypnosis, music
therapy)
2. Acupuncture/acupressure
3. Alprazolam/Lorazepam 0.5-2 mg PO
BREAKTHROUGH EMESIS TREATMENT:
1. Careful evaluation of risk, antiemetic,
chemotherapy, tumor, concurrent disease and
medication factors
2. Ascertain that the best regimen is being
administered for the emetic setting
3. General principle is to add an agent from a
different class to the current regimen:1
Lorazepam 0.5-2 mg PO/IV every 4-6 hrs
Prochlorperazine 10 mg PO/IV every 4-6
hrs or 25 mg suppository every 12 hrs
Promethazine 12.5-25 mg PO/IV every 4-6
hrs
Haloperidol 0.5-2 mg PO/IV every 4-6 hrs
Metoclopromide 10-40 mg PO/IV every 4-6
hrs
Olanzapine 2.5-5 mg PO BID
4. Rectal/IV therapy is preferred, as oral route is
not likely feasible with ongoing vomiting.
5. Multiple concurrent agents, in alternating
schedules or alternating routes may be
necessary.
6. Ensure adequate hydration or fluid repletion.
Simultaneous checking and correcting of
electrolyte imbalance is necessary.

7. If emesis is controlled, continue breakthrough
medications on a schedule. Consider changing
antiemetic therapy to a higher level for the next
cycle.
8. If emesis is not controlled, re-evaluate and
consider dose adjustments and/or switching to a
different therapy.
RADIATION-INDUCED EMESIS
HIGH EMETIC RISK (>90%)

Total body Prophylaxis with 5-HT3 serotonin
receptor antagonist before each fraction
and at least 24 hrs after3
+ Dexamethasone 4 mg PO during
fractions 1-5
MODERATE EMETIC RISK (60-90%)
Upper abdomen Prophylaxis with 5-HT3 serotonin
Upper half body receptor antagonist before each fraction
+ Dexamethasone 4 mg PO during
fractions 1-5
LOW EMETIC RISK (30-60%)
Craniospinal Prophylaxis or rescue with 5-HT3
Head and neck serotonin receptor antagonist before
Lower thorax and pelvis each fraction
If rescue becomes necessary,
prophylactic therapy should be
continued until end of RT
MINIMAL EMETIC RISK (<30%)
Extremities Rescue with dopamine receptor
Breast antagonist or 5-HT3 serotonin receptor
antagonist and continued
prophylactically for each remaining
fraction
CHEMOTHERAPY CONCURRENT WITH RADIOTHERAPY
CONCURRENT WITH Prophylaxis is dictated by the

CHEMOTHERAPY3 emetogenic potential of the
chemotherapy given
REFERENCES
1. National Comprehensive Cancer Network (NCCN). Clinical practice guidelines in oncology: antiemesis.
V 1.2012.
2. Grailla
3. Basch E, Prestrud AA, Hesketh PJ, Kris MG, Feyer MG, et al. Antiemetics: American Society of Clinical
Oncology Clinical Practice Guideline Update. J Clin Oncol 2011;29(31):4189-4198.
4. Grunberg SM, Koeller M. Palonosetron: a unique 5-HT3 receptor antagonist for the prevention of
chemotherapy induced emesis. Expert Opin Pharmacother 2003;4:2297-2303.
5. Rojas C, Thomas AG, Alt J, et al. Palonosetron triggers 5-HT3 receptor internalization and causes
prolonged inhibition of receptor function. Eur J Pharmacol 2010;626:193-199.

6. Rappaport BL, Jordan K, Boice JA, et al. Aprepitant for the prevention of chemotherapy-induced nausea
and vomiting associated with a broad range of moderately emetogenic chemotherapies and tumor types:
a randomized double blind study. Support Care Cancer 2010;18:423-431.
7. Warr DG. Chemotherapy and cancer-related nausea and vomiting. Curr Oncol 2008;15(Suppl 1):S4-S9.
8. Riola F, Herrstedt J, Aapro M, Gralla RJ, Einhorn LH, et al. Guideline update for MASCC and ESMO in
the prevention of chemotherapy- and radiotherapy-induced nausea and vomiting: results of the Perugia
consensus conference. Ann Oncol 2010;21(Suppl 5):232-243.
9. Ruhlmann C, Herrstedt J. Casopitant: a novel NK1-receptor antagonist in the prevention of
chemotherapy-induced nausea and vomiting. Ther Clin Risk Manag 2009;5:375-384.
10. Roscoe JA, Morrow GR, Aapro MS, Molassiotis A, Olver I. Anticipatory nausea and vomiting. Support
Care Cancer 2011;19(10):1533-1538.

II. MANAGEMENT OF FEBRILE NEUTROPENIA
DEFINITION1
NEUTROPENIA – ANC < 500 cells/µL, or < 1000 cells/µL and a predicted decline
to < 500 cells/µL over the next 48 hours
FEBRILE NEUTROPENIA – neutropenia associated with a rise in temperature (>
38.3oC single oral temperature, or > 38oC for > 1 hour, or > 38.5oC axillary
temperature for > 1 hour)
GENERAL PRINCIPLES
1. Risk assessment should be done prior to first cycle of chemotherapy, and

repeated prior to each subsequent cycle.1 In making the decision to use
prophylactic colony stimulating factors (CSFs), oncologists should consider not
only the optimal chemotherapy regimen, but also the individual patient risk
factors and the intention of treatment; that is, curative, prolongation of life, or
symptom control and palliation.
2. The reduction in febrile neutropenia was an important clinical outcome that
justified use of CSFs, regardless of impact on other factors, when the risk of
febrile neutropenia was approximately 20% and no other equally effective
regimen that did not require CSFs was available.
3. Patients should be instructed to immediately consult the hospital when they
develop signs and symptoms of febrile neutropenia (fever, flu-like symptoms,
sore throat, shivering).2
4. Immediate initial assessment, vigorous resuscitation and complete physical
examination should be performed. Laboratory tests should be performed to
determine presence and focus of infection.2
5. Empiric antimicrobial therapy based on risk categorization and local
microbiological data should be initiated immediately.2
RECOMMENDATIONS FOR CSF ADMINISTRATION
1. Primary prophylactic CSF

a. Primary prophylactic CSF is recommended if the patient is considered at
high risk (20% or higher) for febrile neutropenia.1,3 [Level 1a]
Patient Factors Associated with Higher Risk of Developing Febrile

Neutropenia1,3
Age > 65 years old
Poor performance status
Previous episodes of febrile neutropenia
Extensive prior treatment including large radiation ports
Administration of combined chemotherapy
Cytopenia due to bone marrow involvement of tumor
Poor nutritional status
Presence of open wounds or active infections
Advanced stage of cancer
Other serious co-morbidities / immunodeficiency (renal and liver
dysfunction)

Chemotherapy Regimens with a High Risk of Febrile Neutropenia
(> 20%)1,3
Cancer Chemotherapy Regimen
Cervical Paclitaxel-Cisplatin
Epithelial Ovarian Paclitaxel
Docetaxel
Topotecan
Germ Cell Tumors BEP*
Sarcoma Doxorubicin
Melanoma Dacarbazine based combinations
*BEP – Bleomycin, Etoposide, Cisplatin)
b. For chemotherapy regimens associated with intermediate risk (10-20%) of

febrile neutropenia, primary prophylactic CSF should be considered
depending on the presence of clinical, laboratory, patient risk and disease
factors.1,3 [Level IIa]
Chemotherapy Regimens with an Intermediate Risk of Febrile

Neutropenia1,3
Cancer Chemotherapy Regimen
Cervix Cisplatin-Topotecan
Topotecan
Ovarian Topotecan
Carboplatin-Docetaxel
Germ Cell Tumors Cisplatin-Etoposide
BEP → EP*
Sarcoma Docetaxel
*BEP → EP – Bleomycin, Etoposide, Cisplatin followed by Etoposide, Cisplatin
c. For patients receiving chemotherapy with < 10% risk for febrile
neutropenia, primary prophylaxis with CSF is not recommended.1
[Level 2a]
2. Secondary prophylactic CSF should be offered to patients who experienced a

neutropenic complication from a prior cycle of chemotherapy (for which primary
prophylaxis was not given), in which dose reduction may compromise disease-
free or overall survival or treatment outcome.
3. Therapeutic Use of CSF
a. CSFs should not be routinely used for patients with neutropenia who are
afebrile.
b. CSFs should not be routinely used as adjunctive treatment with antibiotic
therapy for patients with fever and neutropenia.
c. CSFs should be considered in patients with fever and neutropenia who are
at high-risk for infection-associated complications or have prognostic factors
predictive of poor clinical outcomes
Poor Prognostic Features:

• Age > 65 years
• Prolonged (> 10 days) neutropenia
• Profound neutropenia (< 0.1 x 109 cells/µL)
• Prior episode of febrile neutropenia

• Uncontrolled primary disease
• Pneumonia
• Invasive fungal infection
• Other clinically documented infections
• Sepsis syndrome (hypotension and multiorgan failure)
• Being hospitalized at the time of development of fever
4. Use of CSF in Patients Receiving Radiotherapy With or Without

Concurrent Chemotherapy
a. Prophylactic use of CSF is not recommended1 in patients receiving

concomitant chemotherapy and radiation therapy, particularly involving the
mediastinum due to an increase risk of complications and death.
b. Therapeutic use of CSF may be considered in patients receiving radiation
therapy alone if prolonged delays secondary to neutropenia are expected.
5. Use of CSF in the Pediatric Population
a. As in adults, the use of CSF is reasonable for the primary prophylaxis of

pediatric patients with a likelihood of febrile neutropenia.
b. The use of CSF for secondary prophylaxis or for therapy should be limited
to high-risk patients
6. CSF Initiation, Duration, Dosing, and Administration
a. CSF should be given 24 to 72 hours after the administration of

chemotherapy.
b. CSF should be continued until reaching an ANC of at least 2-3 x 109
cells/µL.
c. The recommended treatment schedules of G-CSF are as follows:1
[Level 1a]
Formulation Route Dose Frequency Duration
Filgrastim SQ 5 µg/kg daily Up to 38 days
Pegfilgrastim SQ 6 mg once per cycle once per cycle
d. The only indicated use of GM-CSF is for patients with AML. [Level 2b]
e. Pegfigrastim is recommended only for chemotherapeutic regimen given at
least every 2 weeks. [Level 1a]
f. Only filgrastim should be administered in the therapeutic setting.
g. Awareness of common side effects is important: bone, joint or
musculoskeletal pain, and leukocytosis.
RECOMMENDATIONS FOR ANTIBACTERIAL THERAPY FOR FEBRILE

NEUTROPENIA2
1. First line therapy:

a. Oral antibacterial therapy, in the form of single agent quinolones, may be
given to low-risk febrile neutropenia patients. [Level 1a]
• Quinolones should not be given to those who have taken quinolones
as prophylaxis.
e.g. Ciprofloxacin 500-750 mg PO q12 hrs4
Levofloxacin 500-750 mg PO daily4

b. Patients assessed to be high risk should be given intravenous antibiotics.
[Level 1a]
• Monotherapy (e.g. ceftazidime or carbapenem) is as efficacious as
combination therapy.
e.g. Ceftazidime 2 g IV q8 hrs4
Imipenem 500 mg IV q6 hrs4
Meropenem 1 g IV q8 hrs4
• In patients at high risk of prolonged neutropenia and those with
bacteremia, β-lactam + aminoglycoside is preferred.
e.g. Piperacillin/tazobactam 4.5 g IV q6 hrs4 +
Gentamycin / Amikacin, up to 1.5 mg/kg/day
2. Second line therapy: Assess patient after 48 hours of initial antimicrobial

therapy.
a. If patient is afebrile and ANC improves > 0.5 x 109 cells/µL:
• IV antibiotics may be changed to oral antibiotics [Level 2a]
• If on dual therapy, aminoglycoside may be discontinued [Level 3c]
• When cause of infection found, continue on appropriate specific
therapy [Level 2a]
b. If patient remains febrile:
• If clinically stable, continue with initial antibacterial therapy
• If clinically unstable, shift antibacterial therapy
3. Prophylaxis antibiotic:
Prophylactic antibiotic is not recommended for standard dose chemotherapy.1
[Level 2b]
Intermediate and high-risk patients (e.g patients receiving chemotherapy
expected to cause prolonged [> 7 days] neutropenia) should be given
prophylaxis antibiotic in the form of oral quinolones (Levofloxacin) given for 7
days, starting on day 1 of chemotherapy.1,
REFERENCES
1. National Comprehensive Cancer Network (NCCN). Clinical practice guidelines in oncology: Myeloid
growth factors. Version 1.2011.
2. de Naurois J, Novitzky-Basso I, Gill MJ, Marti FM, Cullen MH, et al. Management of febrile neutropenia:
ESMO clinical practice guidelines. Ann Oncol 2010;21(Suppl 5):v252-v256.
3. Aapro MS, Bohlius J, Camceron DA, Lago LD, Donnely JP, et al. 2010 update of EORTC guidelines for
the use of granulocyte-colony stimulating factor to reduce the incidence of chemotherapy-induced febrile
neutropenia in adult patients with lymphoproliferative disorders and solid tumors. Eur J Cancer
2011;47:8-32.
4. National Comprehensive Cancer Network (NCCN). Clinical practice guidelines in oncology: prevention
and treatment of cancer related infections. Version 2.2011.
5. Cullen M, Baijal S. Prevention of febrile neutropenia: use of prophylactic antibiotics. Br J Cancer
2009;101:S11-S14.
6. Smith TJ, Khatcheressian J, Lyman GH, Ozer H, Armitage JO, et al. 2006 update of recommendations
for the use of white blood cell growth factors: an evidence based clinical practice guideline. J Clin Oncol
2006;24(19):3187-3205.
7. Cameron D. Management of chemotherapy associated febrile neutropenia. Br J Cancer 2009;101:S18-
S22.

III. GUIDELINES ON THE USE OF ERYTHROPOESIS STIMULATING AGENTS
Several scientific literature and meta-analyses have established the

associated increased risk for venous thromboembolism with erythropoesis
stimulating agents (ESA) use. This subsequently has been theorized as the possible
mechanism for the observed ESA-associated mortality.1-3
In order to answer issues regarding ESA use, further explore its safety and
efficacy, and provide important evidence-based recommendations, further
prospective randomized clinical studies particularly utilizing revised labeling
formulation of ESA, should still be conducted.4
At present, there are ongoing clinical trials, such as the PREPARE trial and
the EPO-ANE-3010 trial, that assess the effect of ESA on overall survival and
progression free survival.
REFERENCES
1. Bohlius J, Langensiepen S, Schwarzer G, Seidenfeld J, Piper M, et al. Recombinant human
erythropoietin and overall survival in cancer patients: results of a comprehensive meta-analysis. J Natl
Cancer Inst 2005;97:489-498.
2. Amgen. Aranesp (Darbopoetin alfa) Package Insert. Amgen Inc., Thousand Oaks, CA 2009
3. Ortho Procit (Epoetin alfa) Package Insert. Centocor Ortho Biotech Inc: LP, Raritan, KJ 2009.
4. Glaspy J, Crawford J, Vansteenkiste J, Henry D, Rao S, et al. Erythropoesis-stimulating agents in
oncology: a study level meta-analysis of survival and other safety outcomes. Br J Cancer
2010;102:301-315.

IV. RECOMMENDATIONS FOR THE USE OF CHEMOTHERAPY PROTECTANT:
MESNA
MESNA WITH IFOSFAMIDE

Dose Recommendation
Standard dose
Ifosfamide: < 2.5
g/m2/day
Short infusion Daily dose of mesna is calculated at 60% of total
daily dose of ifosfamide administered as three
bolus doses given 15 minutes before and 4 and 8
hours after administration of each ifosfamide
Continuous Mesna is administered as a bolus dose calculated
infusion at 20% of total ifosfamide dose followed by a
continuous infusion of mesna at 40% of the
ifosfamide dose, continuing for 12-24 hours after
completion of ifosfamide
High dose Insufficient data
Ifosfamide: > 2.5 More frequent and prolonged mesna dose
2
g/m /day regimens may be necessary
Oral route mesna Initial IV mesna is given at a bolus dose of 20% of
initial ifosfamide dose; followed by mesna tablets at
a dose 40% of the ifosfamide given at 2 and 6
hours after ifosfamide administration
Total daily dose of mesna is 100% of the total
ifosfamide dose
Patients who vomit within 2 hours of taking oral
mesna should repeat the dose or receive IV mesna
MESNA WITH CYCLOPHOSPHAMIDE (in the setting of stem cell

transplantation)
Dose Recommendation
High dose Mesna plus saline diuresis or forced saline diuresis
cyclophosphamide
REFERENCE
Hensley ML, Hagerty KL, Kewalramani T, Green DM, Meropol NJ, et al. American Society of Clinical
Oncology 2008 clinical practice guideline update: Use of chemotherapy and radiation therapy
protectants. J Clin Oncol 2009;27(1):127-145.

V. MANAGEMENT OF VENOUS THROMBOEMBOLISM
DEFINITION
VENOUS THROMBOEMBOLISM (VTE) is a broad terminology which includes

deep venous thrombosis (DVT), pulmonary embolism (PE), superficial vein
thrombosis (SVT) and thrombosis in other vascular territories
VENOUS THROMBOEMBOLISM PROPHYLAXIS
In-patient Management
1. High-risk individuals should receive VTE prophylaxis.
Risk Factors for VTE

Patient-Related Risk Factors
Older age
Poor performance status
Familial and/or acquired hypercoagulability
Medical co-morbidities: infection, renal disease, pulmonary
disease, congestive heart failure, arterial thromboembolism
Use of exogenous estrogen compounds (HRT, contraceptives,
tamoxifen/raloxifene, diethylstilbestrol)
Obesity (BMI > 35 kg/m2)
Smoking, tobacco
Activity level/exercise
Prior VTE
Cancer-Related Risk Factors

Cancer type: brain, pancreas, stomach, bladder, gynecologic,
lung, lymphoma, myeloproliferative, kidney, metastatic
Active cancer
Advanced stage of cancer
Regional bulky lymphadenopathy with extrinsic vascular
compression
Treatment-Related Risk Factors

Major surgery
Central venous catheter/IV catheter
Chemotherapy with bevacuzimab
Prechemotherapy platelet count > 300,000/µL
Prechemotherapy WBC > 11,000/µL
Hemoglobin < 10 g/dL
Use of erythropoeitc stimulating agents
2. If with no contraindication to anticoagulation, prophylactic anticoagulation

therapy should be administered throughout the duration of hospitalization.

3. If with contraindication to anticoagulation, mechanical devices may be used.
Contraindications to VTE prophylaxis
Recent central nervous system (CNS) bleed, intracranial or
spinal lesion at high risk for bleeding
Active bleeding (major): more than 2 units transfused in 24 hours
Chronic, clinically significant measurable bleeding > 48 hours
Thrombocytopenia (platelets < 50,000/µL
Severe platelet dysfunction (uremia, medications, dysplastic
hemoatopoiesis)
Recent major operation at high risk for bleeding
Underlying coagulopathy
Clotting factor abnormalities
Elevated PT or aPTT
Spinal anesthesia/lumbar puncture
High risk for falls (head trauma)
Ambulatory Management
1. Adult patients diagnosed with cancer who received inpatient VTE prophylaxis
or are ambulatory but are at risk warrant VTE prophylaxis.
2. For patients who underwent surgery, outpatient VTE prophylaxis is
recommended for up to 4 weeks post-surgery.
This is particularly important for patients with:
a. abdomino-pelvic cancer surgery
b. previous history of VTE
c. anesthesia time greater than 2 hours
d. bed rest > 4 days
e. advanced stage disease
f. age > 60 years
3. For patients treated medically, VTE prophylaxis is recommended in high risk
settings (e.g. patients receiving highly thrombotic antiangiogenic therapy)
Options for VTE Prophylaxis
1. Low molecular weight heparin (LMWH)

a. Dalteparin 5,000 unit SQ daily
b. Enoxaparin 40 mg SQ daily
c. Tinzaparin 4,500 units (fixed dose) SQ daily or 75 units/kg SQ daily
2. Fondaparinux 2.5 mg SQ daily
3. Unfractionated heparin 5,000 units SQ 3 times daily
4. Aspirin 81-325 mg daily
5. Warfarin (adjusted to INR 2-3)
6. Mechanical devices
a. intermittent pneumatic venous compression device
b. vena cava filters
c. anti-thromboembolic compression stockings

MANAGEMENT OF VTE
Diagnosis
1. Increased level of clinical suspicion is imperative in the diagnosis of VTE.

The classic clinical symptoms of acute VTE are not always present in cancer
patients.
2. In patients suspected to have VTE, the following should initially be done:
comprehensive clinical history and physical examination, complete blood
count (CBC) with platelet count, prothrombin time (PT), activated partial
thromboplastin time (aPTT), and serum creatinine.
3. Confirmatory tests for Deep Venous Thrombosis (DVT)
a. Duplex venous ultrasonography – gold standard
b. Contrast-enhanced computed tomography (CT)
c. Magnetic resonance imaging (MRI)
d. Invasive venography
4. Confirmatory tests for Splanchnic Vein Thrombosis (SPVT)
a. Duplex ultrasonography
b. Contrast enhanced CT
c. MRI
5. Confirmatory tests for Pulmonary Embolim (PE)
a. Chest radiography
b. CT angiography
c. V-Q lung scan
d. Conventional pulmonary angiography
e. Echocardiogram
f. Serum troponin
Acute Management
Upon diagnosis of VTE and in the absence of contraindications to

anticoagulation, anticoagulation therapy should be initiated immediately and
continued for at least 5-7 days.
LMWH
a. Dalteparin 200 units/kg SQ daily
b. Enoxaparin 1 mg/kg SQ every 12 hours
c. Tinzaparin 175 units/kg SQ daily
Fondaparinux 5 mg (< 50 kg); 7.5 mg (50-100 kg); 10 mg (> 100 kg) SQ
daily
Unfractionated heparin 80 units/kg load IV, then 18 units/kg per hour,
target aPTT of 2-2.5x control
Chronic Management
1. LMWH is preferred for the first 6 months as monotherapy without warfarin for
patients with proximal DVT or PE and prevention of recurrent VTE in patients
with advanced or metasttic cancer.
2. Warfarin (2.5-5 mg daily initially, subsequent dosing based on INR value, to
target INR 2-3)
a. If warfarin is selected for chronic anticoagulation, initiate warfarin
concurrently with the parenteral agent used for acute therapy and
continue both therapies for at least 5 days and until INR > 2 for 24
hours

b. During the transition to warfarin monotherapy, the INR should be
measured at least 2x weekly. Once the patient is on warfarin alone,
the INR should be measured initially at least once weekly, then
gradually decreased to once monthly as long as INR is maintained at
2-3.
Duration of Anticoagulation
1. For patients with deep venous thrombosis (DVT), anticoagulation is

maintained at a minimum of 3-6 months, and 6-12 months for patients with
pulmonary embolism (PE).
2. Indefinite anticoagulation is recommended if there is active cancer or
persistent risk factors.
3. For catheter associated thrombosis, anticoagulate as long as catheter is in
place. Recommended total duration of therapy is at least 3 months.
INDICATIONS FOR FILTER PLACEMENT
1. contraindication to anticoagulation
2. failure of anticoagulation
3. patient noncompliance with prescribed anticoagulation
4. baseline cardiac or pulmonary dysfunction severe enough to make any new
or recurrent PE life threatening
5. patient with documented multiple PE or chronic pulmonary hypertension
REFERENCE:
1. National Comprehensive Cancer Network (NCCN). Venous thromboembolic disease. Version 2.2011.

CANCER PAIN MANAGEMENT
Primary treatment of cancer with surgical resection, radiation therapy or
systemic chemotherapy is often a successful treatment for cancer-related pain.
However, the analgesic therapy added to primary treatment helps improve patient’s
quality of life and can be tapered when it is no longer needed. Pain treatments help
in making the patient compliant with difficult treatment protocols.
WHO METHOD OF RELIEF OF CANCER PAIN
1. Cancer pain can and should be treated.

2. Evaluation and treatment of cancer pain are best achieved by team approach
(multidisciplinary).
3. Determine etiology and type of pain.
a. ETIOLOGY: pain associated with direct tumor involvement; pain
associated with anti-neoplastic therapy; preexisting or concurrent
painful conditions unrelated to cancer
b. TYPE: nociceptive (somatic or visceral), neuropathic, psychogenic
(rare) or mixed
4. Specific aims of cancer pain management:
a. increase hours of pain-free sleep
b. relieve pain when patient is asleep
c. relieve pain when patient is standing or active
5. Treatment begins with an explanation and combines physical and
psychological approaches using both drug and non-drug treatments.
6. Drugs alone give adequate pain relief provided they are the right drug, with
the right dose, given at the right time.
7. Oral route is preferred for analgesics including morphine and they are given
“by the clock” and “by the ladder” with “attention to detail”.

DRUG THERAPY
1. NON-OPIOID
a. Acetaminophen/Paracetamol 650 mg q4H or
b. Aspirin 650 mg q4H or
c. Ketorolac 30 mg PO/IV q8H or
d. Ketoprofen 100 mg PO/IV q8-q12H or
e. Ibuprofen 400-800 mg q6-q8H or
f. Naproxen 250-500 mg q12H or
g. Meloxicam* 7.5-15 mg OD or
h. Celecoxib* 200 mg BID
*Selective cyclooxygenase 2 (COX-2) inhibitors: Until now, much of
the clinical information on the use of COX-2 antagonists is from
rheumatology literature. More research is still needed on the efficacy
and safety of the use of these agents for acute pain relief.
NOTE: If the pain is due to bone metastasis, consider a trial of one of the
Non-Steroidal Anit-Inflammatory Drugs (NSAIDs) rather than
Acetaminophen or Paracetamol.
2. WEAK OPIOIDS
a. Tramadol 50-100 mg immediate release tablet/capsules q4-6H
b. Tramadol 100, 150, and 200 mg sustained release tablet form q8-
12H
Note: Maximum daily dose: 600 mg
3. STRONG OPIOIDS
a. Morphine Plain (10, 20, and 30 mg) tablets; 5-10 mg PO q4-6H;
titrate upwards at increments of 25-50% every 24 hours until
adequate analgesia is obtained. There is no ceiling dose for
morphine and most other opioids. The dosing interval should be
increased or decreased to provide continuous analgesia with
minimal sedation. Decrease doses in debilitated patients and in
those with kidney and liver derangements. A rescue dose for
breakthrough pain should be given prn q1-2H at ¼ the regular
dose.
b. Morphine (Sustained Release Preparation) ex: MS Contin (10,
30, 60 and 100 mg tablets); given at equi-analgesic doses q8-12H
interval for better compliance, when appropriate daily Morphine
dose requirements have been established. Always prescribe
immediate release or Morphine Plain for treatment of breakthrough
pain.
c. Morphine Parenteral; prepared as morphine drip by infusion for
terminally ill patients; dose starts at 0.5 – 1 mg/hr and titrated
closely depending on response; rescue doses may be given 2-3
mg IV q2-3H for breakthrough pain. Do not give intramuscularly
(IM).
d. Oxycodone ex: Oxycontin (10, 20, 40 and 80 mg tablets); has
higher oral bioavailability than Morphine; given at equi-analgesic
doses q8-12H.
e. Transdermal Fentayl (Duragesic Patch 12, 25, 50, 75, and 100
mcg/hr); applied as patch over hairless skin and replaced q3 days;
dose requirements depend on previous opioid use (dose
conversion table available); used when oral intake of opioid is

difficult (ex. vomiting); Morphine can be administered
intravenously or subcutaneously for breakthrough pain.
OPIOID SIDE EFFECTS
1. Constipation (less than 1 BM in 3 days): increase fiber consumption, increase

fluid intake, mild laxative like milk of magnesia, cathartic drugs such as
bisacodyl for severe constipation
2. Nausea and vomiting: manage with anti-emetics such as metaclopromide;
may shift to a less emetic drug like fentanyl patch at equianalgesic dose of
present opioid
3. Sedation: Tolerance to this effect develops rapidly. If persistent, may
decrease dose of opioid.
4. Other effects: Opioids may cause myoclonus, hallucinations and seizures.
OVERDOSAGE
Pinpoint pupils, respiratory depression, hypotension

In more severe cases, circulatory failure and deepening coma
TREATMENT
Primary attention should be given to the establishment of a patent airway and

institution of assisted or controlled ventilation. Administer Naloxone 0.4 mg IV.
Repeat after 2-3 minute intervals as necessary, or by infusion of 2 mg in 500 ml of
normal saline or 5% dextrose (0.004mg/ml). The infusion should be run in
accordance with the patient’s response.
ADJUVANT DRUGS: These are prescribed as indicated, usually for a neuropathic

pain component.
1. ANTIDEPRESSANTS: Imipramine 25-50 mg tab at bedtime

Doxepin 25-150 mg tab at bedtime
2. ANTICONVULSANTS: Carbamazepine 200 mg tab BID (max: 1,200
mg/day)
Gabapentin 100 mg cap TID (max: 3,600 mg/day)
3. STEROIDS: Dexamethasone 16-96 mg/day PO/IV
ADJUVANT NEURAL BLOCKADE
“Application of invasive measures to the 10-30% of patients who fail oral therapy
can relieve nearly all cancer pain”
Regional techniques such as nerve blocks for cancer pain are intended to be
analgesic adjuvants and not as definitive treatments. These allow patients to
lower drug dosages, thereby reducing side effects. Neither the primary physician
nor the pain specialist should promise permanent relief, since the patients’
disease may progress and spread. Interventional anesthetic and neurosurgical
techniques are therapeutic options for managing cancer pain that is uncontrolled
by conventional pharmacotherapy. These techniques include intraspinal drug
administration, neuromodulation using spinal cord stimulators and minimally
invasive procedures such as vertebroplasty. Some patients may benefit from

neusosurgical techniques such as dorsal rhizotomy, anterolateral cordotomy and
cingulotomy to ablate peripheral or central pathways of pain.
TOOLS FOR MEASUREMENT
1. Categorical Scale
None : “walang kirot”
Mild : “konting kirot”
Moderate: “katamtamang kirot”
Severe : “malubhang kirot”
2. Visual Analog Scale +/- Numeric Scale (0-10)
|_____________________________________________|
No Pain Worst Pain
REFERENCES:
1. World Health Organization. Expert Committee Report 1990. Cancer Pain Relief and Palliative Care. Technical
Series 804. Geneva: World Health Organization 1990
2. Foley K. The Treatment of cancer pain. N Engl J Med 1985; 313-93.
3. Portenoy RK, Hagen, NA. Breakthrough pain: definition, prevalence and characteristics. Pain 1990;41; 273-281
4. Krames E. Med Clin North America. 1999;83: 787-808

APPENDIX A
LEVELS OF EVIDENCE AND GRADES OF RECOMMENDATION
I. Oxford Centre for Evidence-based Medicine Levels of Evidence (May 2001)
Level Therapy/Prevention, Prognosis Diagnosis Differential Economic and

Aetiology/Harm diagnosis/symptom decision analysis
prevalence study
1a SR (with homogeneity*) SR (with SR (with homogeneity*) of SR (with homogeinity*) of SR (with homogeneity*)
of RCTs homogeneity*) of Level 1 diagnostic studies; prospective cohort studies of Level 1 economic
inception cohort prospective cohort studies studies
studies; CDR† CDR† with 1b studies
validated in different from different clinical
populations centres
1b Individual RCT (with Individual inception Validating** cohort study Prospective cohort study Analysis based on
narrow Confidence cohort study with > with good††† reference with good follow-up**** clinically sensible costs
Interval‡) 80% follow-up; CDR† standards; or CDR† tested or alternatives;
validated in a single within one clinical centre systematic review(s) of
population the evidence; and
including multi-way
sensitivity analyses
1c All or none§ All or none case- Absolute SpPins and All or none case-series Absolute better-value or
series SnNouts†† worse-value analyses
††††
2a SR (with homogeneity* ) SR (with SR (with homogeneity*) of SR (with homogeneity*) of SR (with homogeneity*)
of cohort studies homogeneity*) of Level > 2 diagnostic 2b and better studies of Level > 2 economic
either retrospective studies studies
cohort studies or
untreated control
groups in RCTs
2b Individual cohort study Retrospective cohort Exploratory** cohort study Retrospective cohort Analysis based on
(including low quality study or follow-up of with good†††reference study, or poor follow-up clinically sensible costs
RCT; e.g. < 80% follow- untreated control standards; CDR† after or alternatives; limited
up) patients in an RCT; derivation, or validated review(s) of the
Derivation of CDR† or only on split-sample§§§ or evidence, or single
validated on split- databases studies; and including
sample§§§ only multi-way sensitivity
analyses
2c "Outcomes" Research; "Outcomes" Research Ecological studies Audit or outcomes
Ecological studies research
3a SR (with homogeneity*) SR (with homogeneity*) of SR (with homogeneity*) of SR (with homogeneity*)
of case-control studies 3b and better studies 3b and better studies of 3b and better studies
3b Individual Case-Control Non-consecutive study; or Non-consecutive cohort Analysis based on
Study without consistently study, or very limited limited alternatives or
applied reference population costs, poor quality
standards estimates of data, but
including sensitivity
analyses incorporating
clinically sensible
variations.
4 Case-series (and poor Case-series (and poor Case-control study, poor Case-series or Analysis with no
quality cohort and case- quality prognostic or non-independent superseded reference sensitivity analysis
control studies§§ ) cohort studies***) reference standard standards
5 Expert opinion without Expert opinion without Expert opinion without Expert opinion without Expert opinion without
explicit critical appraisal, explicit critical explicit critical appraisal, or explicit critical appraisal, or explicit critical appraisal,
or based on physiology, appraisal, or based on based on physiology, based on physiology, or based on economic
bench research or "first physiology, bench bench research or "first bench research or "first theory or "first
principles" research or "first principles" principles" principles"
principles"

NOTES:
Users can add a minus-sign "-" to denote the level of that fails to provide a conclusive answer because of:
EITHER a single result with a wide Confidence Interval (such that, for example, an ARR in an RCT is not statistically significant
but whose confidence intervals fail to exclude clinically important benefit or harm)
OR a Systematic Review with troublesome (and statistically significant) heterogeneity.
Such evidence is inconclusive, and therefore can only generate Grade D recommendations.
* By homogeneity we mean a systematic review that is free of worrisome variations (heterogeneity) in the directions
and degrees of results between individual studies. Not all systematic reviews with statistically significant
heterogeneity need be worrisome, and not all worrisome heterogeneity need be statistically significant. As noted
above, studies displaying worrisome heterogeneity should be tagged with a "-" at the end of their designated level.
† Clinical Decision Rule. (These are algorithms or scoring systems which lead to a prognostic estimation or a
diagnostic category.)
‡ See note #2 for advice on how to understand, rate and use trials or other studies with wide confidence intervals.
§ Met when all patients died before the Rx became available, but some now survive on it; or when some patients died
before the Rx became available, but none now die on it.
§§ By poor quality cohort study we mean one that failed to clearly define comparison groups and/or failed to measure
exposures and outcomes in the same (preferably blinded), objective way in both exposed and non-exposed
individuals and/or failed to identify or appropriately control known confounders and/or failed to carry out a sufficiently
long and complete follow-up of patients. By poor quality case-control study we mean one that failed to clearly define
comparison groups and/or failed to measure exposures and outcomes in the same (preferably blinded), objective
way in both cases and controls and/or failed to identify or appropriately control known confounders.
§§§ Split-sample validation is achieved by collecting all the information in a single tranche, then artificially dividing this
into "derivation" and "validation" samples.
†† An "Absolute SpPin" is a diagnostic finding whose Specificity is so high that a Positive result rules-in the diagnosis.
An "Absolute SnNout" is a diagnostic finding whose Sensitivity is so high that a Negative result rules-out the
diagnosis.
‡‡ Good, better, bad and worse refer to the comparisons between treatments in terms of their clinical risks and benefits.
††† Good reference standards are independent of the test, and applied blindly or objectively to applied to all patients.
Poor reference standards are haphazardly applied, but still independent of the test. Use of a non-independent
reference standard (where the 'test' is included in the 'reference', or where the 'testing' affects the 'reference') implies
a level 4 study.
†††† Better-value treatments are clearly as good but cheaper, or better at the same or reduced cost. Worse-value
treatments are as good and more expensive, or worse and the equally or more expensive.
** Validating studies test the quality of a specific diagnostic test, based on prior evidence. An exploratory study collects
information and trawls the data (e.g. using a regression analysis) to find which factors are 'significant'.
*** By poor quality prognostic cohort study we mean one in which sampling was biased in favour of patients who already
had the target outcome, or the measurement of outcomes was accomplished in <80% of study patients, or outcomes
were determined in an unblinded, non-objective way, or there was no correction for confounding factors.
**** Good follow-up in a differential diagnosis study is >80%, with adequate time for alternative diagnoses to emerge (eg
1-6 months acute, 1 - 5 years chronic)
II. GRADES OF RECOMMENDATION

A Consistent level 1 studies
B Consistent level 2 or 3 studies or extrapolations from level 1 studies
C Level 4 studies or extrapolations from level 2 or 3 studies
D Level 5 evidence or troublingly inconsistent or inconclusive studies of any level
"Extrapolations" are where data is used in a situation which has potentially clinically important differences than the original
study situation.

III. GRADE PRO
Quality Level Definition Study Design
High We are very confident that the true effect lies close to that of Randomized Controlled Trials
the estimate of the effect
Moderate We are moderately confident in the effect estimate. The true
effect is likely to be close to the estimate of the effect, but
there is a possibility that it is substantially different
Low Our confidence in the effect estimate is limited: The true Observational Studies
effect may be substantially different from the estimate of the
effect
Very Low We have very little confidence in the effect estimate: The
true effect is likely to be substantially different from the
estimate of the effect
REFERENCES
1. Canadian Task Force on the Periodic Health Examination: The periodic health examination. CMAJ 1979;121:1193-1254.
2. Sackett DL. Rules of evidence and clinical recommendations on use of antithrombotic agents. Chest 1986 Feb; 89 (2
suppl.):2S-3S.
3. Cook DJ, Guyatt GH, Laupacis A, Sackett DL, Goldberg RJ. Clinical recommendations using levels of evidence for
antithrombotic agents. Chest 1995 Oct; 108(4 Suppl):227S-230S.
4. Yusuf S, Cairns JA, Camm AJ, Fallen EL, Gersh BJ. Evidence-Based Cardiology. London: BMJ Publishing Group, 1998.
5. Balshem H, Helfand M, Schunemann HJ, Oxman AD, Kunz R, et al. GRADE guidelines 3: Rating the quality of evidence. J
Clin Epidemiol 2011;64:401-406.

NATIONAL CAPITAL REGION REGION I
Rainerio S. Abad, MD Teresita P. Agbanlog, MD – Baguio City
Genalin F. Amparo, MD Richard Ronald B. Cacho, MD – Pangasinan/La Union
Leo Francis N. Aquilizan, MD Ruth Judith V. Cristobal, MD – Ilocos Sur
Edna C. Banta, MD Victorino C. Garcia Jr. - Pangasinan
Aida J. Bautista, MD Yvonne T. Soriano, MD – Baguio City/La Union
Doris R. Benavides, MD REGION II
Glenn B. Benitez, MD Melchor C. dela Cruz, Jr., MD – Isabela/Nueva Vizcaya
Isidro B. Benitez, MD REGION III
Manuel N. Borja, MD Ronald Agustine O. Campos, MD – Pampanga
Judith G. Cabanela, MD Agnes M. Gaddi, MD – Pampanga
Teresita B. Cardenas, MD Jocelyn Z. Mariano, MD – Bulacan/Pampanga
Carolyn Z. Castro, MD Elmer R. Santos, MD – Balanga, Bataan
Melinda M. Cayabyab, MD Jaynet D. Tan, MD – Tarlac, Tarlac
Percida S. Cocos, MD Corazon R. Valdez, MD – Olongapo City, Zambales
Lilli May T. Cole, MD REGION IV
Benjamin D. Cuenca, MD Coleta B. Arias, MD – Lucena City, Quezon
Elsie R. Dancel, MD Belina A. Antinero– Batangas City, Batangas
Rey H. delos Reyes, MD Andrew Rouldan B. Buizon, MD – Dasmarinas, Cavite
Efren J. Domingo, MD Aina S. Diaz, MD – Sta. Rosa, Laguna
Rommel Z. Dueñas, MD Belen T. Garana, MD – Lucena City Quezon
Aris Luke I. Dungo, MD Arlene B. Huevos, MD – San Pablo City, Laguna
Ana Victoria V. Dy Echo, MD Gina P. Motil, MD – Lucena City, Quezon
Emilio Glenn B. Evangelista, MD Elizabeth E. Strebel, MD – Biñan, Laguna
Jay Arnold F. Famador, MD Menandro A. Villadelgado, MD – Tanauan, Batangas
Victoria S. Fernando, MD Salvador Luis R. Villanueva, MD – Los Baños, Laguna
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Maria Julieta V. Germar, MD Rona F. Rañola, MD – Legaspi, Albay
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Genara M. Limson, MD Arnold P. Liwag, MD – Iloilo City/Bacolod City
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Marie Aleli D. Malig, MD Patricia Ann S. Coronel, MD – Cebu
Manuel S. Manabat, MD Pherdes E. Galbo, MD – Cebu
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Ma. Lilibeth L. Sia Su, MD Edelyn A. Badilla, MD – Tagum City
Renee Vina G. Sicam, MD Carol Marjorie P. Flavier, MD – Davao City
Luciano S.J. Sotto, MD Concepcion D. Rayel, MD – Davao City
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Elizabeth E. Strebel, MD Constancia Wilhelmina S. Torres, MD – Davao City
Ma. Patricia L. Sun, MD REGION XII
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Ma. Cynthia F. Tan, MD Myra Joy G. Maduramente, MD – General Santos
German C. Tan-Cardoso, MD
Rafael S. Tomacruz, MD
Jean Anne B. Toral, MD
John-David V. Zamora, MD

APPENDIX C
2009 FIGO STAGING OF GYNECOLOGIC CANCERS
CERVICAL CANCER
STAGE I The carcinoma is strictly confined to the cervix (extension to the corpus would be
disregarded).
Stage IA Invasive carcinoma that can be diagnosed only by microscopy, with deepest
invasion < 5 mm and largest extension < 7 mm
Stage IA1 Measured stromal invasion < 3.0 mm in depth and extension of < 7.0 mm
Stage IA2 Measured stromal invasion of > 3.0 mm and not > 5.0 mm with an extension of not
> 7.0 mm
Stage IB Clinically visible lesions limited to the cervix uteri, or preclinical cancers greater
than Stage IA*
Stage IB1 Clinically visible lesions < 4.0 cm in greatest dimension
Stage IB2 Clinically visible lesions > 4.0 cm in greatest dimension
STAGE II The carcinoma invades beyond the cervix but not to the pelvic wall or to the lower
third of the vagina
Stage IIA Without parametrial invasion
Stage IIA1 Clinically visible lesions < 4.0 cm in greatest dimension
Stage IIA2 Clinically visible lesions > 4.0 cm in greatest dimension
Stage IIB With obvious parametrial invasion
STAGE III The carcinoma extends to the pelvic wall and/or involves the lower third of the
vagina and/or causes hydronephrosis or nonfunctioning kidney
Stage IIIA Tumor involves lower third of the vagina, with no extension to the pelvic wall
Stage IIIB Extension to the pelvic wall and/or hydronephrosis or non-functioning kidney
STAGE IV The carcinoma has extended beyond the true pelvis or has clinically involved
(biopsy proven) the mucosa of the bladder or rectum. A bullous edema, as such,
does not permit a case to be allotted to Stage IV.
Stage IVA Spread of growth to adjacent organs
Stage IVB Spread to distant organs
* All macroscopically visible lesions – even with superficial invasion – are allotted to stage IB
carcinomas. Invasion is limited to a measured stromal invasion with a maximal depth of 5 mm and a
horizontal extension of not > 7 mm. Depth of invasion should not be > 5 mm taken from the base of the
epithelium of the original tissue – superficial or glandular. The depth of invasion should always be
reported in mm, even in those cases with early (minimal) stromal invasion (~ 1 mm).
** On rectal examination, there is no cancer-free space between the tumor and the pelvic wall. All cases
with hydroneprhosis or non-functioning kidney are included, unless they are known to be due to another
cause.

ENDOMETRIAL CANCER
STAGE I* Tumor confined to the corpus uteri
Stage IA No or less than half myometrial invasion
Stage IB Invasion equal to or more than half the myometrium
STAGE II* Tumor invades cervical stroma, but does not extend beyond the uterus**
STAGE III* Local and/or regional spread of the tumor
Stage IIIA* Tumor invades serosa of the corpus uteri and/or adnexae#
Stage IIIB* Vaginal and/or parametrial involvement#
Stage IIIC* Metastases to pelvic and/or para-aortic lymph nodes#
Stage IIIC1* Positive pelvic lymph nodes
Stage IIIC2* Positive para-aortic lymph nodes with or without positive pelvic lymph nodes
STAGE IV* Tumor invades bladder and/or bowel mucosa, and/or distant metastases
Stage IVA* Tumor invasion of bladder and/or bowel mucosa
Stage IVB* Distant metastases, including intra-abdominal and/or inguinal lymph nodes
*Either G1, G2, G3
** Endocervical glandular involvement only should be considered as Stage I and no longer Stage II.
#Positive cytology has to be reported separately without changing the stage.

UTERINE SARCOMA
A. LEIOMYOSARCOMA
STAGE I Tumor limited to the uterus
Stage IA < 5 cm
Stage IB > 5 cm
STAGE II Tumor extends to the pelvis
Stage IIA Adnexal involvement
Stage IIB Tumor extends to extrauterine pelvic tissue
STAGE III Tumor invades abdominal tissues (not just protruding into the abdomen)
Stage IIIA One site
Stage IIIB > one site
Stage IIIC Metastasis to pelvic and/or para-aortic lymph nodes
STAGE IV
Stage IVA Tumor invades bladder and/or rectum
Stage IVB Distant metastasis
B. ESS AND ADENOSARCOMAS

STAGE I Tumor limited to the uterus
Stage IA Tumor limited to the endometrium/endocervix with no myometrial invasion
Stage IB Less than or equal to half myometrial invasion
Stage IC More than half myometrial invasion
STAGE II Tumor extends to the pelvis
Stage IIA Adnexal involvement
Stage IIB Tumor extends to extrauterine pelvic tissue
STAGE III Tumor invades abdominal tissues (not just protruding into the abdomen)
Stage IIIA One site
Stage IIIB > one site
Stage IIIC Metastasis to pelvic and/or para-aortic lymph nodes
STAGE IV
Stage IVA Tumor invades bladder and/or rectum
Stage IVB Distant metastasis
C. CARCINOSARCOMAS
Should be staged as carcinomas of the endometrium

OVARIAN CANCER
STAGE I Growth limited to the ovaries
Stage IA Growth limited to one ovary No ascites present containing malignant cells; No
tumor on the external surface; Capsule intact
Stage IB Growth limited to both ovaries No ascites present containing malignant cells; No
tumor on the external surfaces; Capsules intact
Stage IC Tumor Stage IA or IB but with tumor on surface of one or both ovaries; or with
capsule ruptured; or with ascites present containing malignant cells or with positive
peritoneal washings
STAGE II Growth involving one or both ovaries with pelvic extension
Stage IIA Extension and/or metastases to the uterus and/or tubes
Stage IIB Extension to other pelvic tissues
Stage IIC Tumor Stage IIA or IIB but with tumor on surface of one or both ovaries; or with
capsule(s) ruptured; or with ascites present containing malignant cells or with
positive peritoneal washings
STAGE III Tumor involving one or both ovaries with peritoneal implants outside the pelvis
and/or positive retroperitoneal or inguinal nodes; superficial liver metastases
equals Stage III. Tumor is limited to the true pelvis but with histologically proven
malignant extension to small bowel or omentum
Stage IIIA Tumor grossly limited to the true pelvis with negative nodes but with histologically
confirmed microscopic seeding of abdominal peritoneal surfaces
Stage IIIB Tumor of one or both ovaries with histologically confirmed implants of abdominal
peritoneal surfaces, none exceeding 2 cm in diameter; nodes are negative
Stage IIIC Abdominal implants greater than 2 cm in diameter and/or positive retroperitoneal or
inguinal nodes
STAGE IV Growth involving one or both ovaries with distant metastases. If pleural effusion is
present, there must be positive cytology to allot a case to Stage IV. Parenchymal
liver metastases equals Stage IV.

FALLOPIAN TUBE CANCER
STAGE 0 Carcinoma in situ (limited to tubal mucosa)
STAGE I Growth limited to the fallopian tubes
Stage IA Growth is limited to one tube, with extension into the submucosa and/or muscularis
but not penetrating the serosal surface; no ascites
Stage IB Growth is limited to both tubes, with extension into the submucosa and/or muscularis
but not penetrating the serosal surface; no ascites
Stage IC Tumor either Stage IA or IB, but with tumor extension through or onto the tubal
serosa or with ascites present containing malignant cells or with positive peritoneal
washings
STAGE II Growth involving one or both fallopian tubes with pelvic extension
Stage IIA Extension and/or metastases to the uterus and/or ovaries
Stage IIB Extension to other pelvic tissues
Stage IIC Tumor either Stage IIA or IIB and with ascites present containing malignant cells or
with positive peritoneal washings
STAGE III Tumor involving one or both fallopian tubes with peritoneal implants outside the pelvis
and/or positive retroperitoneal or inguinal nodes. Superficial liver metastasis equals
Stage III. Tumor appears limited to the true pelvis but with histologically proven
malignant extension to small bowel or omentum
Stage IIIA Tumor is grossly limited to the true pelvis with negative nodes but with histologically
confirmed microscopic seeding of abdominal peritoneal surfaces
Stage IIIB Tumor involving one or both tubes with histologically confirmed implants of abdominal
peritoneal surfaces, none exceeding 2 cm in diameter. Lymph nodes are negative.
Stage IIIC Abdominal implants greater than 2 cm in diameter and/or positive retroperitoneal or
inguinal nodes
STAGE IV Growth involving one or both fallopian tubes with distant metastases. If pleural
effusion is present, there must be positive cytology to be Stage IV. Parenchymal liver
metastasis equals Stage IV.

VULVAR CANCER
A. FIGO STAGING FOR VULVAR CANCER

STAGE I Tumor confined to the vulva
Stage IA Lesions < 2 cm in size, confined to the vulva or perineum and with stromal invasion <
1.0 mm*, no nodal metastasis
Stage IB Lesions > 2 cm in size or with stromal invasion > 1.0 mm*, confined to the vulva or
perineum, with negative nodes
STAGE II Tumor of any size with extension to adjacent perineal structures (1/3 lower urethra,
1/3 lower vagina, anus) with negative nodes
STAGE III Tumor of any size with or without extension to adjacent perineal structures (1/3 lower
urethra, 1/3 lower vagina, anus) with positive inguino-femoral lymph nodes
Stage IIIA (i) With 1 lymph node metastasis (> 5 mm), or (ii) 1-2 lymph node metastasis(es) (< 5
mm)
Stage IIIB (i) With 2 or more lymph node metasteses (> 5 mm), or (ii) 3 or more lymph node
metastases (< 5 mm)
Stage IIIC With positive nodes with extracapsular spread
STAGE IV Tumor invades other regional (2/3 upper urethra, 2/3 upper vagina), or distant
structures
Stage IVA Tumor invades any of the following: (i) upper urethral and/or vaginal mucosa, bladder
mucosa, rectal mucosa, or fixed to pelvic bone, or (ii) fixed or ulcerated inguino-
femoral lymph nodes
Stage IVB Any distant metastasis including pelvic lymph nodes
* The depth of invasion is defined as the measurement of the tumor from the epithelial-stromal junction
to the adjacent most superficial dermal papilla to the deepest point of invasion.
B. MICROSTAGING FOR VULVAR MELANOMAS
LEVEL CLARK CHUNG BRESLOW

I Intraepithelial Intraepithelial < 0.76 mm
II Into papillary dermis < 1.0 mm from granular layer 0.76 – 1.50 mm
III Filling dermal papillae 1.1 – 2.0 mm from granular layer 1.51 – 2.25 mm
IV Into reticular dermis > 2.0 mm from granular layer 2.26 – 3.00 mm
V Into subcutaneous fat Into subcutaneous fat > 3.00 mm
VAGINAL CANCER
STAGE I The carcinoma is limited to the vaginal wall.
STAGE II The carcinoma has involved the subvaginal tissue but has not extended to the pelvic
wall.
STAGE III The carcinoma has extended to the pelvic wall.
STAGE IV The carcinoma has extended beyond the true pelvis or has involved the mucosa of
the bladder or rectum; bullous edema as such does not permit a case to be allotted
to Stage IV.
Stage IVA Tumor invades bladder and/or rectal mucosa and/or direct extension beyond the true
pelvis
Stage IVB Spread to distant organs

APPENDIX D
USEFUL MARKERS IN GYNECOLOGIC PATHOLOGY
I. Lineage – Specific Markers
A. Epithelial Markers – Keratin

1. K20 (Type I, MW 46 kDa ) and K7 (Type II, MW 54 kDa )
o Endometrioid and serous carcinoma of the ovary are K7 positive and K20 negative
o Majority of mucinous carcinoma of the ovary, especially those of colonic type, are K7
positve or K20 positive
o In mixed germ cell tumor, K7 is selectively expressed by trophoblastic components
2. K8 (Type II, MW 52 kDa), K18 (Type I, MW 45 kDa), K19 (Type I, MW 40 kDa)

o Most adenocarcinoma of gynecologic origin and germ cell tumor (except dysgerminoma)
are positive with K8 and K18
o In granulosa cell tumor, keratin staining is negative, when positive it is very focal and
subtle
o Keratin is negative in Leydig cells and steroid tumors. Sertoli cell tumor often is positive
with K18 and K8.
3. K4 (Type II, MW 58 kDa), K13 (Type I, MW 51 kDa)

o Suggest the diagnosis of poorly differentiated endometrioid carcinoma
o The cells for Brenner tumors as well as those that comprise transitional carcinoma
predominantly express K13
B. Mesothelial marker - Calretinin

o The majority of metastatic adenocarcinoma of gynecologic origin as well as ovarian – type
serous papillary cancer of the peritoneum are expected be negative
o It is frequently positive in reactive mesothelial cells and mesothelioma but negative in the
majority of adenocarcinoma
C. Mesenchymal marker - Vimentin

o Co-expression of vimentin and keratin is seen almost always or very frequent, in certain
types of carcinoma: these includes renal cell carcinoma, papillary of the thyroid,
endometrial carcinoma and serous tumor of the ovary
o Sex cord stromal tumor such as granulose cell tumor are also vimentin positive but keratin
negative
D. Muscle markers
1. Desmin – in rhabdomyeloblastic cells such as in MMMT, desmin is a very sensitive marker
2. Actin – An ubiquitous fibrillary protein thinner than desmin is present in many epithelial and
non epithelial cells as a cytoskeletal protein
3. H-caldesmon – More specific for smooth muscle difference as compared with actin and
desmin
4. Myoglobin, Myo D1, Myogenin
E. Sex cord marker - Inhibin

o α-inhibin is widely accepted as a marker for sex cord tumor especially granulosa cell tumor
o Also expressed in normal granulosa cell, luteinized thecal cell and hilus cell in normal ovary
o Adnexal tumor of probable wolffian origin are also reported to be positive
o
F. Urothelial marker - Uroplakin
o Transitional cell carcinoma is negative but Brenner tumor including malignant Brenner
tumor are uroplakin positive

G. Glial marker - Glial Fibrillary Acidic Protein (GFAP)
o Occasionally detected in subpopulation of tumor cells for serous (ovary and extraovarian)
and endometrial adenocarcinoma but not in mucinous or clear cell carcinoma
o In ovarian teratoma, GFAP positivity has been reported in cartilaginous component as well
as in glial component
H. Neuroendocrine and Melanocytic Markers

1. Chromogranin, Synaptophysin – Good universal marker for neuroendocrine difference
2. Neuron-Specific Enolase (NSE) – Nonspecificity limits its diagnostic usefulness
3. HMB 45 – More specific melanocytic marker
4. S-100 protein
o Although specific of neural, melanocytic and Schwann cells, many other cells such as
chondrocytes, lymphocytes, Langerhan’s cells of skin and myeloepithelial cells
express S-100 protein
o Serous cancer of the ovary shows high frequency of S-100 positive cells
o Endometrial and clear cells cancer may be also S-100 positive; in contrast mucinous
tumor is rarely positive
I. Trophoblastic markers
1. Keratins and keratin 7
2. Human chorionic gonadotropin (hCG) – In ovarian germ cell tumors including embryonal
carcinoma, mixed germ cell tumor containing choriocarcinoma and dysgerminoma with
syncitiotrophoblastic giant cells
3. Human placental lactogen (hPL) – Produced by syncitial and intermediate trophoblast in
the normal placenta. Cytotrophoblast is devoid of hPL
4. Human placental alkaline phosphatase (hPLAP) – Detected in the serum of pregnant
women and in patient with certain malignancies such as germ cell tumor, cancer of the
lungs, stomach, pancreas, heart and ovary
5. Inhibin, CD 146
II. Tumor Associated Antigen and Oncofetal Marker
A. Carbohydrate Antigen 125 (CA125) (OC125) and CA19–9

o Elevated in more than 80% of ovarian cancer patients
o Useful in monitoring ovarian cancer patients but it is not specific of ovarian CA
o Mucinous tumor show much less frequent positivity (about 20% or less)
o Positive in approximately 30% of clear cell and endometrioid carcinoma
o CA 19-9 is a glycopeptide cancer associated antigen similar to CA 125
B. Tumor Associated Glycopeptide (TAG 72) (B 72.3) o

o Frequently positive in epithelial malignancy including ovarian cancer as well as colorectal
and breast
C. Human milk fat globule (HMFG) and Epithelial membrane antigen (EMA)
o Antibodies to HMFG and EMA react with virtually all epithelial tumor of the ovary including
both benign and malignant type
D. Alpha fetoprotein (AFP)

o Observed most commonly in patients with hepatocellular carcinoma and germ cell tumor

E. Carcinoembryogenic Antigen (CEA)
o Negative in all normal ovarian tissue
o Most frequently positive in mucinous cancer (70-80%)
o In serous tumor, CEA is much less frequent positive (about 20%)
o Endometrioid carcinoma (especially in the areas of squamous differentiation),
undifferentiated carcinoma, and Brenner tumor are also frequently CEA positive
o Clear cell carcinoma is less frequently CEA positive
III. Hormone receptors: Estrogen and Progesterone receptors

o As many as 80% of normal ovarian tissue (surface epithelium and stroma), benign neoplastic
lesion and carcinoma, especially endometrioid cancer expresses ER/PR
o Differentiation of tumors is correlated with ER expression but not with PR expression
o Rare example of malignant Brenner tumor and ovarian ependymoma showing PR but not ER
positivity
o A yolk sac tumor has been reported to be negative for ER/PR by immunohistocytochemistry
IV. Prognostic markers

A. Ki67 – In ovarian cancer, Ki67 ranged from 1-59% and showed correlation with advanced
stage and patient survival but not with ER/PR status
B. P53 – Serous adenocarcinoma of ovary has a high frequency of positive p53 especially in
advanced stage serous adenocarcinoma, however no significant correlation with p53 and
survival has been noted. Benign tumors and borderline tumors are usually negative of p53.
C. HER2/Neu (C-ERB B2) – Negative or rarely and weakly positive in normal ovary; Strongly
positive in reported ovarian cancer with similar frequency as in breast cancer, that is,
approximately one third.

APPENDIX E
DIFFERENTIAL DIAGNOSES BY IMMUNOHISTOCHEMISTRY
I. Ovarian Endometrioid Carcinoma Versus Serous Carcinoma
Endometrioid carcinoma; Keratin 4/5+

Serous carcinoma: Keratin 4/5-
Note: Because endometrioid carcinoma of the ovary shows frequent squamous differentiation, the
detection of subtle squamous differeniration favors the diagnosis of endometrioid carcinoma.
Expression of K4 and K5 (high molecular weight keratins) may precede morphologically identifiable
squamous differentiation.
II. Ovarian Endometrioid Carcinoma Versus Metastatic Carcinoma of Gastrointestinal (GI) Tract
Ovarian endometrioid carcinoma: keratin 7+, keratin 20-

Metastatic carcinoma from GI: keratin 7-, keratin 20+
Note: K7-, K20+ is most characteristic for colonic adenocarcinomas. Gastric Carcinomas are
frequently K7+, K20+ or K7-, K20+. Pancreatic carcinoma is usually K7+, K20+.
III. Ovarian Endometrioid Carcinoma with Sertoliform Features Versus Sex Cord-Stromal Tumor
Ovarian endometrioid carcinoma: keratin 7+, inhibin-

Sex cord-stromal tumor: keratin 7-, inhibin+
IV. Ovarian Micinous Carcinoma Versus Metastatic Mucinous Carcinoma from Gastrointestinal
Tract
Ovarian mucinous carcinoma: keratin 7+, Keratin 20+/-.

Metastatic mucinous carcinoma from colon: Keratin 7-, Keratin 20+
Note: K7-, K20+ is characteristic of colonic adenocarcinoma. Gastric carcinoma is frequently K7+, K
20+ or K7-, K20+. Pancreatic carcinoma is usually K7+, K20+.
V. Ovarian Serous Carcinoma Versus Epithelial Peritoneal Mesothelioma
Ovarian serous carcinoma: keratin 5/6-, thrombomodulin-, calretinin-

Peritoneal mesothelioma: keratin 5/6+, thrombomodulin+, calretinin+
VI. Ovarian Clear Cell Carcinoma Versus Dysgerminoma
Ovarian clear cell carcinoma: keratin+, EMA+

Dysgerminoma: keratin-, EMA-
Note: Both could show predominantly clear cell features with intracytoplasmic glycogen. Although
there are few reports describing dysgerminoma and keratin expression, the foregoing keratin profile
is based on our experience and is extrapolated from studies on testicular seminomas.
VII. Ovarian Clear Cell Carcinoma Versus Metastatic Renal Cell Carcinoma
Ovarian clear cell carcinoma: keratin +, vimentin-

Metastatic renal cell carcinoma: keratin+, vimentin+
VIII. Ovarian Clear Cell Carcinoma Versus Yolk Sac Tumor
Ovarian clear cell carcinoma: α-fetoprotein- (or +/-), LeuM-1 (CD15)+

Yolk sac tumor: α-fetoprotein+, LeuM1- (mostly)

IX. Ovarian Transitional Cell Carcinoma (Ovarian Carcinoma with TCC Features) Versus
Metastatic Transitional Cell Carcinoma
Ovarian TCC: keratin 20-, uroplakin-, thrombomodulin-

Metastatic TCC: keratin 20+, uroplakin+, thrombomodulin+
X. Granulosa Cell Tumor Versus Poorly Differentiated Carcinoma
Granulosa cell tumor: inhibin+, keratin- (or +/-), vimentin+

Poorly differentiated carcinoma: inhibin-, keratin+, vimentin+/-.
XI. Ovarian Germ Cell Tumors: Nontrophoblastic Versus trophoblastic Elements
Trophoblastic elements: keratin 7+, HCG+, hPLAP+

Nonseminomatous, nontrophoblastic elements: keratin 7-, HCG-, hPLAP+
XII. Ovarian Germ Cell Tumor: Dysgerminomatous Elements Versus Embryonal Carcinoma and
Yolk Sac Tumor
Dysgerminoma: keratins-, -fetoprotein-, hPLAP+

Embryo carcinoma and yolk sac tumor: keratins+, α-fetoprotein+, hPLAP+
Note: Although there are few reports describing ovarian germ cell tumors and keratin expression,
the foregoing keratin profile is based on our experience and is extrapolated from studies on
testicular seminomas.

APPENDIX F
DEFINITION OF RESPONSE TO TREATMENT
RESPONSE WHO Change in Cross Product (CP) RECIST Change in Maximal Diameter (MD)
Complete
Complete resolution of all evidence of
Response Complete resolution of all evidence of disease
disease lasting at least 1 month
(CR)
A decrease of 50% in the product of the
Partial A decrease of 30% in the baseline sum longest
diameters (maximal and minimal) of all
Response diameters of all measurable disease* without
measurable lesions lasting at least 1 month
(PR) the development of new lesions
without the development of new lesions
Stable A decrease of < 50% or an increase of < A decrease of < 30% or an increase of < 20%
Disease 25% in the product of the diameters of all in the baseline sum longest diameters of all
(SD) measurable disease measurable disease*
An increase of 25% in the measurable An increase of 20% in the baseline sum
Progression lesions as described above or the longest diameters of all measurable disease* or
identification of new lesions the identification of new lesions
*Measurable Disease is defined as solid tumors assessed by CT scan (>10 mm) or by ultrasonography
(> 20 mm). Nonmeasurable disease is defined as lesions measuring < 10 mm by CT scan or < 20 mm
by ultrasonography. Nonmeasurable disease included cystic lesions and ascites and also patients in
whom the response assessment is performed by different imaging techniques.

APPENDIX G
PERFORMANCE STATUS SCORING
ECOG* Score GOG** Score Karnofsky Score Activity Level

Fully active; Unrestricted activities of
0 0 90-100
daily living.
Ambulatory but restricted in strenuous
1 1 70-80
activity.
Ambulatory but capable of self-care;
2 2 50-60 Unable to work. Out of bed greater than
50% of waking hours.
Limited self-care; Confined to bed or
3 3 30-40 chair 50% of waking hours; Needs
special assistance.
4 4 10-20 Completely disabled; No self-care.
5 5 0 Dead
*ECOG – Eastern Cooperative Oncology Group, also sometimes called The WHO/Zubrod score **
GOG – Gynecologic Oncology Group
RECOMMENDATIONS
Surgery Chemotherapy Radiotherapy
: ECOG Score 0 – 2 : ECOG Score 0 – 2 : ECOG Score 0 – 4

APPENDIX H
USEFUL WEBSITE ADDRESSES
Society of Gynecologic Oncologists of

http://www.sgop.org
the Philippines
National Cancer Institute http://www.nci.nih.gov
CancerNet (PDQ and Cancerlit) http://cancernet.nci.nih.gov
Clinical Trials http://www.cancertrials.nci.nih.gov
Surveillance, Epidemiology, and End
http://www-seer.ims.nci.nih.gov
Results (SEER) program
Common Terminology Criteria for
http://ctep.cancer.gov/reporting/ctcnew.html
Adverse Events v3.0 (CTCAE)
National Institute of Health http://www.nih.gov
PubMed (Medline) http://www.ncbi.nlm.nih.gov/PubMed
Women’s Cancer Network http://www.wcn.org
Gynecologic Cancer Foundation http://www.sgo.org.gcf
SHARE: Self Help for Women with Breast
http://www.noah.cuny.edu/providers/cancare/html
and Ovarian Cancer
National Asian Women’s Health
http://nawho.org
Organization
Center for Cervical Health http://cervicalhealth.org
The DES Cancer Network http://www.descancer.org
National Cervical Cancer Coalition http://www.nccc-online.org
National Ovarian Cancer Coalition http://www.ovarian.org
American Cancer Society http://www.cancer.org
American Institute for Cancer Research http://www.aicr.org
CancerBacUp http://www.cancerbacup.org.uk
Cancer Care, Inc. http://www.cancercare.org
Cancer Information Network http://www.cancernetwork.com/index2.htm
Cochrane Cancer Network http://www.canet.demon.co.uk
Medicine Online http://www.meds.com
Medical Conferences and Meetings http://pslgroup.com/medconf.htm
MedWeb http://www.medwebplus.com
National Comprehensive Cancer Network http://www.cancernetwotk.com
Network for Oncology Communication and
http://www.nocr.com
Research
OncoLink http://www.oncolink.upenn.edu
Oncology Online – Oncology Therapeutics
http://205.239.179.160.81
Network
WebMD http://my.webmd.com
Yahoo http://dir.yahoo.com/Health/Medicine/Oncology
MD Digests http://php2.silverplatter.com/physicians/digest.htm
http://www.medscape.com/home/topics/oncology/oncology
Medscape Oncology
.html
World Oncology Network http://www.worldoncology.net/oncology_journals.htm
Asia & Oceania Federation of Obstetrics
http://www.aofog.org
and Gynaecology
American College of Obstetricians and
http://www.acog.org
Gynecologists
International Federation of Gynecology
http://www.figo.org
and Obstetrics
American Society for Clinical Oncology http://www.asco.org
European Society for Medical Oncology http://www.esmo.org

Federation of European Cancer Societies http://www.fecs.be
Society of Gynecologic Oncologists http://www.sgo.org
European Society of Gynaecological
http://www.esgo.org
Oncology
International Gynecologic Cancer Society http://www.igcs.org
International Society of Gynecological
http://www.isgyp.com
Pathologists
International Federation for Cervical
http://www.ifcpc.org
Pathology and Colposcopy
American Society for Colposcopy and
http://www.asccp.org
Cervical Pathology
EUropean Research Organisation on
http://www.eurogin.com
Genital Infection and Neoplasia
Gynecologic Oncology Group http://www.gog.org
European Organisation for Research and
http://www.eortc.be
Treatment of Cancer
International Society for the Study of
http://www.isstd.org
Trophoblastic Diseases
Centers for Disease Control and
http://cdc.gov
Prevention
Food and Drug Administration http://www.fda.gov
MD Anderson Cancer Center http://www.mdanderson.org
Memorial Sloan-Kettering Cancer Center http://www.mskcc.org

Sgop 2012

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Society of Gynecologic Oncologists of the Philippines

Clinical Practice Guidelines

A Recognized Affiliate Subspecialty Society of P GS

SGOP TREATMENT GUIDELINES 2012

The field of obstetrics and gynecology is a very dynamic one. Numerous

REY H. DELOS REYES, MD, MHSA, FPOGS, FSGOP, FPSCPC

SGOP TREATMENT GUIDELINES 2012

GIL S. GONZALEZ, MD, FPOGS, FSGOP, FPSCPC

SGOP TREATMENT GUIDELINES 2012

• The clinical recommendations contained in this manuscript is the sole ownership

EFREN J. DOMINGO, MD,PhD, FPOGS, FSGOP, FPSCPC

SGOP TREATMENT GUIDELINES 2012

CECILIA L. LLAVE, MD, PhD

MA. JULIETA V. GERMAR, MD

MA. LILIBETH L. SIA SU, MD

REY H. DELOS REYES, MD, MHSA

PHILIPPINE BOARD OF GYNECOLOGIC ONCOLOGY

Cecilia L. Llave, MD, PhD

SGOP TREATMENT GUIDELINES 2012

2012 GENERAL MEMBERSHIP

ABAD, Rainerio S. DUEÑAS, Rommel Z. OBLEPIAS, Virgilio R.

DY ECHO, Ana Victoria V. TAN, Jaynet D. AMPARO, Genalyn F.

ABELARDO, Agustina D. DALMACIO-CRUZ, Adelaida D. ORTIN, Teresita S.

CHANNEN, William PECORELLI, Sergio THOMAS, Gillian M.

SGOP TREATMENT GUIDELINES 2012

ENDOMETRIAL CANCER & UTERINE SARCOMAS

OVARIAN & FALLOPIAN TUBE CANCERS

VULVAR & VAGINAL CANCERS

PREVENTION & TREATMENT OF COMPLICATIONS

SGOP TREATMENT GUIDELINES 2012

1. Cervical cancer is diagnosed by biopsy.1

2. Cervical cancer is staged clinically. All recommendations are based on the

3. If clinically indicated, proctosigmoidoscopy and cystoscopy should be done to

4. Special diagnostic imaging studies may be done to guide treatment planning:

5. The roles of laparoscopic or robotic surgery in staging and treatment need

6. The primary treatment of early stage cervical cancer is either surgery or

7. The primary treatment of late stage cervical cancer is concurrent

8. For patients who are unable to receive chemotherapy, radiation treatment

9. Lymphovascular space invasion (LVSI) does not alter the FIGO

10. Adenocarcinomas have shown no significant difference in clinical behavior

SGOP TREATMENT GUIDELINES 2012

I. Biopsy Proven Premalignant Lesions12

Notes: Diagnostic excisional procedures include the following: cold-knife conization

II. Malignant Disease

SGOP TREATMENT GUIDELINES 2012

STAGE STATUS TREATMENT

b. PGH Section of Gynecologic Oncology Eligibility Criteria for Radical Vaginal

SGOP TREATMENT GUIDELINES 2012

b. Surgical intervention (EHBSO or mRHBSO) is an option for the following cases:

c. Concurrent chemotherapy and pelvic EBRT (with no midline shield) followed

d. Ongoing trial EORTC 55994: Randomized phase III study of neoadjuvant

SGOP TREATMENT GUIDELINES 2012

FINAL HISTOPATHOLOGY REPORT OF CERVICAL CANCER SPECIMENS

SURGICO-PATHOLOGIC PROGNOSTIC FACTORS

PROGNOSTIC FACTORS ADJUVANT TREATMENT

SGOP TREATMENT GUIDELINES 2012

Note: If PALS not

If with distant metastases:

SPECIAL CLINICAL SITUATIONS

A. INCIDENTAL FINDING OF INVASIVE CERVICAL CANCER AFTER SIMPLE

Pathologic Review Result Treatment

SGOP TREATMENT GUIDELINES 2012

1. The 2009 FIGO staging applies.