SGOP 2008 Guidelines On Management PDF

Society of Gynecologic Oncologists of the Philippines
(Foundation), Inc.
Clinical Practice Guidelines
Fifth Edition
August 2008
TABLE OF CONTENTS
Page No
Foreword 2
Preamble 3
SGOP Officers 2008-2010 4
PBGO 2008-2010 4
SGOP General Membership 5
Ad Hoc Committee for the Clinical Practice Guidelines 2008 6
CLINICAL PRACTICE GUIDELINES
Cervical Cancer 7
Endometrial Hyperplasia 19
Endometrial Cancer 20
Uterine Sarcomas 32
Ovarian Cancer 36
Fallopian Tube Cancer 46
Vulvar Cancer 47
Vaginal Cancer 56
Cancer Pain Management 59
Prevention and Treatment of Complications 63
APPENDIXES
Appendix A Levels of Evidence and Grades of Recommendation 73
Appendix B Geographical Distribution of Gynecologic Oncologists 75
Appendix C Staging of Gynecologic Malignancies 76
Appendix D Useful Markers in Gynecologic Pathology 79
Appendix E Differential Diagnosis by Immunohistochemistry 82
Appendix F Definition of Response to Treatment 83
Appendix G Performance Status Scoring 84
Appendix H Useful Web Addresses 84
SGOP TREATMENT GUIDELINES 2008 1

FOREWORD
The proper management of any malignancy requires an appreciation of its many

clinical presentations and the natural history of these types of cancers. Accurate diagnosis
and staging are essential to proper management. This is especially true of gynecologic
malignancies. It is therefore important that a well researched and studied practice
guideline, such as this, is formulated.
The preparation and planning of this latest clinical guidelines was conceived when it
became apparent that there is a proliferation of new information in the proper management
of gynecologic malignancies. This clinical practice guideline is a product of the hard work
of the committee headed by Efren Domingo, M.D., our Immediate Past President, to whom
we should all be thankful. They did a thorough literature survey, collation and synthesis of
data in their several meetings, before presenting their output to the SGOP Membership
during our Midyear Convention in April this year. The continued support given by Bristol
Myers Squibb in the publication of this guideline is also well appreciated.
This is 5th in a series of publications that surveys the entire domain of current
clinical management of gynecologic malignancies. It is hoped that we all find the
information stimulating and useful in our approach to the management of patients with
gynecologic cancer.
REY H. DE LOS REYES, M.D., FSGOP

President
Society of Gynecologic Oncologists of the Philippines (Foundation), Inc.
2008-2010

PREAMBLE
This publication, The Clinical Practice Guidelines of the SGOP is intended to fulfill
the following objectives. 1.) To equip the gynecologic oncologist with the sufficient
knowledge about the screening, diagnosis and management of cancer of the female
genital tract. 2.) To provide the gynecologic oncologist a quick reference guide which may
be used in his/her daily clinical practice.
It is recommended that the specific diagnostic or therapeutic procedures mentioned

in this guide be performed only by the gynecologic oncologist with certified training. It is
recommended also that the gynecologic oncologists optimize referral amongst their
colleague gyne-oncologists where his or her knowledge be incomplete of deficient in the
diagnostic and therapeutic procedures encountered.
It is hoped that this guide become a companion of the gynecologic oncologist in the
prevention and actual treatment of cancer of the female genital tract. May this be a source
of information that may be used to capture disease early, to have a disease be treated
correctly and promptly by the best hands with the best training.
Efren J. Domingo, M.D.,Ph.D.

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

THE SOCIETY OF GYNECOLOGIC ONCOLOGISTS OF THE PHILIPPINES
(FOUNDATION), INC.
OFFICERS
2008 2010
REY H. DELOS REYES, MD, MHSA

President
GIL S. GONZALEZ, MD
Vice-President
MA. CYNTHIA F. TAN, MD

Secretary
MA. LILIBETH L. SIA SU, MD

Treasurer
MARY CHRISTINE F. PALMA, MD

PRO
EFREN J. DOMINGO, MD, PhD

Immediate Past President
BOARD OF DIRECTORS
Teresita B. Cardenas, MD Jericho Thaddeus P. Luna, MD
Benjamin D. Cuenca, MD Manuel S. Manabat, MD
Aris Luke I. Dungo, MD Concepcion D. Rayel, MD
Cecilia L. Llave, MD, PhD Rafael S. Tomacruz, MD
PHILIPPINE BOARD OF GYNECOLOGIC ONCOLOGY
Gil S. Gonzalez, M.D.

Chairman
Members
Cecilia L. Llave, M.D., Ph.D.
Virgilio R. Oblepias, M.D.
THE SOCIETY OF GYNECOLOGIC ONCOLOGISTS OF THE PHILIPPINES

(FOUNDATION), INC.
2008 GENERAL MEMBERSHIP
FELLOWS
ABAD, Rainerio S. DOMINGO, Efren J. RIVERA, Wilhelmina D.
AGBANLOG, Teresita P. DUNGO, Aris Luke I. SABADO, Grace D.
ALBANO, Amuerfina D. EVANGELISTA, Emilio Glenn B. SALES-DIAZ, Aina R.
AQUILIZAN, Leo Francis N. GADDI, Agnes M. SAN JUAN, Filomena S.
BANTA, Edna C. GARANA, Belen T. SANTOS, Elmer R.
BAUTISTA, Aida J. GERMAR, Ma. Julieta Corazon V. SANTOS, Helen Grace T.
BENAVIDES, Doris R. GONZALES, Ma. Gay M. SIA SU, Ma. Lilibeth L.
BENITEZ, Glenn B. GONZALEZ, Gil S. SOLIS, Constancia Wilhelmina T.
BENITEZ, Isidro B. LLAVE, Cecilia L. SORIANO, Yvonne T.
BORJA, Manuel N. LIMSON, Genara M. SOTTO, Luciano S.J. Sotto
BRESNAN, Alma M. LIWAG, Arnold P. SOTTO, Rene V.
BUIZON, Andrew Rouldan B. LUNA, Jericho Thaddeus P. SULAY, Raymond S.
CABANELA, Judith G. MADURAMENTE, Myra Joy G. SUN, Ma. Patricia L..
CACHO, Richard Ronald B. MANABAT, Manuel S. TAN, Ma. Cynthia F.
CARDENAS, Teresita B. MANALO, Augusto M. TAN-CARDOSO, German C.
CAYABYAB, Melinda M. MARIANO, Jocelyn Z. TOMACRUZ, Rafael S.
COCOS, Percida S. MERCADER, Evangeline M. TORAL, Jean Ann B.
COLE, Lilli May T. MERCADO, Fe Marissa G. TUPAS, Ma. Lora C.
CORONEL, Patricia Ann S. MORAN, Jose B. VALDEZ, Corazon R.
CUENCA, Benjamin D. MOTIL, Gina P. VILLADELGADO, Menandro A.
DANCEL, Elsie, R. OBLEPIAS, Virgilio R. VILLANUEVA, Salvador Luis R.
DELA CRUZ, Melchor C. Jr. PALMA, Mary Christine F. YAMBAO, Helen D.
DELOS REYES, Rey H. RAOLA, Rona F. ZAMORA, John-David V.
DIY, Norma L. RAYEL, Concepcin D.
DIPLOMATES
ARIAS, Coleta B. DUEAS, Rommel Z. GALBO, Pherdes E.
CAMPOS, Ronald Agustine O. FAMADOR, Jay Arnold F. GANZON, Esther Rhadamanthine V. Jr.
CRISTOBAL, Ruth Judith V. FERNANDO, Victoria S. HUEVOS, Arlene B.
DE CASTRO, Marie Aleli R. FLAVIER, Carol Marjorie P. STREBEL, Elizabeth E.
PUA, Scheryl B..
AFFILIATE FELLOWS
ABELARDO, Agustina D. DULAY, Robert P. NUQUI, Elizabeth A.
AVILA, Jose Ma. C. JACINTO, Elizabeth K. PADILLA-CRUZ, Angeles
CABALUNA, Ma. Lourdes Josefina K. JOCSON, Milagros T. PALO-GARCIA, Fe L.
CALAGUAS, Miriam Joy C. KRINGS, Cathy L. 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.
DALMACIO-CRUZ, Adelaida D. ORTIN, Teresita S.
HONORARY FELLOWS
CHANNEN, William PECORELLI, Sergio THOMAS, Gillian M.
MANAHAN, Constantino P. FRIEDLANDER, Michael

AD HOC COMMITTEE FOR THE SGOP 2008 CLINICAL PRACTICE GUIDELINES
CHAIR
Efren J. Domingo, M.D., Ph.D.
ADVISERS
Luciano S.J. Sotto, M.D.
Augusto M. Manalo, M.D.
Genara A. Manuel-Limson, M.D.
Virgilio R. Oblepias, M.D.
COORDINATORS
Jericho Thaddeus P. Luna, M.D.
Maria Julieta M. Victoriano-Germar, M.D.
CERVICAL CANCER
Ma. Lilibeth L. Sia Su, M.D.
Maria Julieta M. Victoriano-Germar, M.D.
Fellows
Carolyn R. Zalameda-Castro, M.D.
Rosalyn C. Balaquit, M.D.
ENDOMETRIAL CANCER & UTERINE SARCOMAS

Efren J. Domingo, M.D., Ph.D.
Jean Anne B. Toral, M.D.
Fellows
Christine Joy G. Garcia, M.D.
Ana Victoria V. Dy Echo, M.D.
OVARIAN & FALLOPIAN TUBE CANCERS

Filomena S. San Juan, M.D., Ph.D.
Jericho Thaddeus P. Luna, M.D.
Fellows
Mary Evangeline A. Villa-Mercado, M.D.
Helen N. Retuta-Amorin, M.D.
VULVAR & VAGINAL CANCERS

Glenn B. Benitez, M.D.
Doris R. Benavides, M.D.
Fellows
Renee Vina G. Sicam, M.D.
Edelyn A. Badilla, M.D.
PAIN
Ma. Lourdes Josefina K. Cabaluna, M.D.
Fellow
Maura G. Catabijan, M.D.
PREVENTION & TREATMENT OF COMPLICATIONS

Elizabeth E. Espino-Strebel, M.D.
Carol Marjorie H. Pacioles-Flavier, M.D.
Victorino C. Garcia Jr., M.D.
Fellow
Mary Lilia Bernadette V. Tinio, M.D.

CERVICAL CANCER
GENERAL GUIDELINES
1. Cervical cancer is diagnosed by biopsy1(Benedet 2006).

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

LESION TREATMENT
SATISFACTORY COLPOSCOPY UNSATISFACTORY COLPOSCOPY
1. Preceded by ASCUS, ASC-H, LSIL: Diagnostic excisional
Follow up every 6-12 months procedures:LEEP/CONE11 [Level 3a]
11,12(ALTS Follow up study 2003) [Level 2b]
CIN 1
2. Preceded by HSIL, AGC: Follow up
every 6 months OR Diagnostic
excisional Procedure 11,12
[Level 3b]
1. Cryotherapy 11 [Level 1a] Diagnostic excisional procedures:
LEEP/CONE 11,13,14 (Massad 2001/Dunn 2003)
CIN 2,3
2. Conization: Cold-Knife Cone Biopsy [Level 2a]
or LEEP/LLETZ 11,13,14 [Level 1a]

II. Malignant Disease
STAGE STATUS TREATMENT
1. Desirous of pregnancy, no lymphovascular space invasion(LVSI)
a. Negative margins observe1,15-19 (Benedetti Panici 2007 review) [Level 1b]
b. Positive margins - repeat cone biopsy1,15-19 [Level 1b]
2. Not desirous of pregnancy

a.Extrafascial hysterectomy (EH) with or without bilateral salpingo-
Good surgical risk
oophorectomy ( BSO) 1,15-19 [Level 1b]
b. Vaginal extrafascial hysterectomy ( BSO)15 [Level 1b]
Stage 0a c. If positive for lymphovascular space invasion(LVSI): modified
Stage I A 1 a radical hysterectomy( BSO) with bilateral pelvic lymph node
dissection 1,15,21(Benedetti Panici 2007 Review, Koliopoulous 2007 )
review[Level2b]
1.Negative margins- observe1,15-19 (Benedetti Panici 2007 review)
[Level 1b]
2.Positive margins-
Poor surgical risk a. Repeat Cone/LEEP 1,15-19 (Benedetti Panici 2007 review)
b. Intracavitary Radiotherapy (Brachytherapy): High Dose Rate
(HDR) or Low Dose Rate (LDR)
3. Positive LVSI pelvic EBRT + brachytherapy [Level 3c]
1. Desirous of pregnancy, no LVSI
Radical trachelectomyc and extra-peritoneal or
Laparoscopic pelvic lymphadenectomy22-24, [Level 2b]
Good surgical risk
` 2. Not desirous of pregnancy
Stage IA2 Modified radical hysterectomy (MRH), bilateral pelvic lymph
node dissection (BLND) BSO16,24 [Level 1b]
Pelvic External Beam Radiotherapy (EBRT) b + Brachytherapy
Poor surgical risk
[Complete RT] 21(Koliopoulous 2007) [Level2b]
Notes:
a. Stages 0, IA1 and IA2 are diagnosed by cone biopsy (cold-knife conization or LEEP/LLETZ).1
b. Pelvic EBRT includes the upper half of the vagina.
c. Radical vaginal trachelectomy (Dargent) and laparoscopic lymphadenectomy23 inclusion criteria:
1. Desire to preserve fertility
2. No clinical evidence of impaired fertility
3. FIGO Stage 1a2-1B1
4. Lesion size less than 2 cms
5. No evidence of pelvic lymph node metastasis
6. No LVSI
7. Informed consent

STAGE STATUS TREATMENT
Good surgical risk 1. Radical hysterectomy (RH), BLND Paraaortic lymph node
sampling BSO25-26 [Level 1a]
2. Concurrent chemotherapy a and pelvic EBRT + Brachytherapy
(Chemoradiation)27,28 [Level 1a]
Stage IB1 , IIA
3. Radical vaginal hysterectomy BSO and extra peritoneal or
(tumor diameter
laparoscopy assisted pelvic lymphadenectomy b 29,30[Level IC]
< 4 cms.)
4. Radical trachelectomyc and extra-peritoneal or Laparoscopic pelvic
lymphadenectomy21-24, [Level 2b]
Concurrent chemotherapy a and pelvic EBRT + Brachytherapy
Poor surgical risk
(Chemoradiation)27,28 [Level 1a]
Notes:
a. Standard Chemotherapy drug to use for concurrent treatment with radiotherapy:
Cisplatin 40 mg/ m2 given weekly for 6 courses during pelvic EBRT 1,4-9 [Level 1a]
b. PGH Section of Gynecologic Oncology Eligibility Criteria for Radical Vaginal Hysterectomy:
1. Selected Stage 1B1 IIA (low risk for parametrial or nodal metastasis, tumor size less than 2 cm, no evidence
of metastasis by imaging and metastatic work-up)
2. Pelvic organ prolapse
c. Radical vaginal trachelectomy and laparoscopic lymphadenectomy23 inclusion criteria:

1. Desire to preserve fertility
2. No clinical evidence of impaired fertility
3. FIGO Stage 1a2-1B1
4. Lesion size less than 2 cms
5. No evidence of pelvic lymph node metastasis
6. No LVSI
7. Informed consent
d. May proceed with RHBSO + lymphadenectomy even with the presence of resectable lymph node metastasis
with uninvolved parametria.31,32
STAGE TREATMENT
1. Concurrent chemotherapya and pelvic EBRT + Brachytherapy
(Chemoradiation) b 6,33-35 [Level 1b]
2. Neoadjuvant chemotherapy (three rapidly delivered courses of
platinum-based chemotherapy), followed by RHBLND BSO +
adjuvant postoperative radiation or chemoradiation36,37[Level 1b].
Stage IB 2 , II A Chemotherapeutic options include:
(tumor diameter > 4 cms) a. Cisplatin-Paclitaxel
b. Cisplatin Vinblastine Bleomycin (PVB)
c. Cisplatin Ifosfamide
3. Pelvic EBRT concurrent with chemotherapya followed by RHBSO
with selective lymphadenectomy (Level 2b) 38 (Toral 2005)
4. Primary radical hysterectomy and bilateral pelvic
lymphadenectomy, which usually needs to be followed with

adjuvant chemoradiation1,39,40 (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:
b. Surgical intervention (EHBSO or Type II RHBSO) is an option for the following cases:
1. After protracted chemoradiation (>8 weeks) 38,41 (Level 2b)
2. Bulky residual disease (> 2 cm) at the end of radiation therapy 42,43
c. Pelvic EBRT (with no midline shield) concurrent with chemotherapy followed by RHBSO with
selective lymphadenectomy is an option especially for areas with no brachytherapy facilities
(consensus-based)
d. Ongoing trial EORTC 55994 : Randomized phase III study of neoadjuvant chemotherapy (3 courses
cisplatin based) followed by surgery vs. concomitant radiotherapy and chemotherapy in FIGO Ib2,
IIa > 4 cm or IIb cervical cancer
STAGE TREATMENT
a,b
Concurrent chemotherapy and pelvic EBRT + Brachytherapy
Chemoradiation4-7,9,39,40 [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: extended field radiotherapy (EFRT)+ brachytherapy +
concurrent cisplatin chemotherapy44-46 [Level 2A]
If with evidence of distant metastases on imaging and/or biopsy:
Systemic combination chemotherapy and individualized radiotherapy
1[Level 2A]
Notes:
a. Standard chemotherapy drug to use for concurrent treatment with radiotherapy:
b. Other chemotherapy regimens used for concurrent treatment with radiotherapy (For locally advanced cervical
cancer)
1. Carboplatin 300 mg/ m2 (AUC 3.9) every 3 weeks or 60-90mg/m2 (AUC 2) weekly 47,48
2. Cisplatin 40 mg/ m2 and Paclitaxel 40 mg/ m2 weekly for 6 cycles 49
c. Ongoing trial GOG 219:A Phase III, Randomized Trial of Weekly Cisplatin and Radiation Versus Cisplatin and
Tirapazamine and Radiation in Stage IB2, IIA, IIB, IIIB and IVA Cervical Carcinoma Limited to the Pelvis
FINAL HISTOPATHOLOGY REPORT OF CERVICAL CANCER SPECIMENS:

1. Histologic type
2. Histologic grade
3. Lymphovascular space involvement (LVSI)
4. Parametria

5. Vaginal cuff to include distance from tumor to margin
6. Stromal invasion divided into thirds
7. Endomyometrial invasion
8. Lymph nodes, to include number and location, and/or Perinodal fat involvement
9. Adnexa, if BSO performed
10. For MICA, vertical and horizontal invasion in mm
11. For CIN/CIS post-conization (cold-knife or LEEP/LLETZ), status of margins and +/- LVSI
12. Mark a cone specimen at the 12 oclock position
13. No mention of stage of disease in histopathologic reports
SURGICO-PATHOLOGIC PROGNOSTIC FACTORS
PROGNOSTIC FACTORS ADJUVANT TREATMENT

1. Tumor size > 2cm** Concurrent chemotherapy and pelvic EBRT 50,51 [Level Ib: 4
cms] Consensus based
2. Greater than 1/3 stromal invasion Concurrent chemotherapy and pelvic EBRT 30,50,52 Delgado1990, Sedlis
1999, Rotman2006)[Level IB]
3. Positive lines of resection Parametrium Concurrent chemotherapy and

pelvic EBRT52Delgado 1990 [Level 1B]
Surgical margins Concurrent chemotherapy and
pelvic EBRT52[Level 1B]
Vaginal cuff or < 2 cm Concurrent chemotherapy, pelvic
tumor free margin EBRT and brachytherapy
[consensus-based]
4. Lymph node metastasis Pelvic Concurrent chemotherapy and
pelvic EBRT 8,50,52-53 [Level 1B]
Note: If para-aortic sampling not

performed, may do EFRT if MRI
or CT Scan confirms periaortic
lymphadenopathy.
Para-aortic and Common Concurrent chemotherapy and
iliac EFRT29,52-55[Level 2A]
5. Lymphovascular space invasion Concurrent chemotherapy and pelvic EBRT 30,48,51,52 Delgado1990,
(LVSI) Sedlis 1999, Rotman2006) [Level IB]
6. Endomyometrial invasion Concurrent chemotherapy and pelvic EBRT52[Level C]

7. Biopsy proven abdominal Systemic chemotherapy and Individualized radiotherapy
metastasis 52,53[Level 2A]
CLINICAL SITUATIONS
A. INCIDENTAL FINDING OF INVASIVE CANCER AFTER SIMPLE HYSTERECTOMY

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

Pathologic Review Result Treatment
Stage 1A1, no LVSI Observation 1 [ Level 2A]
Stage 1A1 with LVSI, Stage 1A2 and IB1 Concurrent chemotherapy and pelvic EBRT +
Negative margins, negative imaging studies Brachytherapy Chemoradiation 54 [ Level 2A]
Complete parametrectomy with upper

vaginectomy with pelvic lymphadenectomy +/-
paraaortic lymph node sampling 54 [ Level 2A]
Stage 1A1 with LVSI, Stage 1A2 and above Concurrent chemotherapy and pelvic EBRT +
Positive margins, gross residual disease, positive Brachytherapy chemoradiation55[ Level 2A]
imaging studies
If paraaortic lymphadenopathy: give EFRT55
[ Level 2A]
B. In Association with Pregnancy

MRI may be done to assess extent of disease 10
Age of Gestation Early Stage (Stage I II A) Late Stage ( Stage II B IV)
Good surgical risk
Early Pregnancy RHBLND BSO 10 Chemoradiation 10
up to 20 weeks AOG Poor surgical risk
Chemoradiation 10
May delay treatment till
after delivery 1
20-28 weeks AOG Antepartal Chemoradiation
chemotherapy(Cisplatin
based ) then CS 1
Late Pregnancy Good surgical risk
After 28 weeks CS RHBLND BSO 1,10 *CS followed by Chemoradiation 10
Poor surgical risk
* Perform Cesarean Antepartal chemotherapy(Cisplatin based ) then
CS followed by
Section (CS) 10 at best CS 56
Chemoradiation 56
time of fetal survival
Notes:
1. There is no standard definition on what constitutes significant treatment delay.1
2. The duration of the treatment delay should be influenced by clinical stage and histopathologic findings of the tumor,
gestational age at diagnosis, and the parents desire regarding their unborn child. Close clinical surveillance is
mandatory.1
3. No long term studies have looked into giving neoadjuvant chemotherapy in an attempt to prevent disease progression
4. Delivery should be performed not later than 34 weeks of gestation.1

OTHER CLINICAL SITUATIONS
e. Ovarian conservation 1. Age 45years old57[Level 2B]
during radical surgery 2. Early stage disease (up to IIA)57,58[Level 2B]
in young patients57 3. Squamous large cell histology57-58,61-64 [Level 2B]
4. Cervical stromal involvement inner 1/3 57 [Level 2B]
5. No family history of ovarian or breast cancer1,58
6. Tumor size 2 cm60,62
7. No lymph node metastasis or LVSI60-64
8. Absence of extracervical / corpus spread 62,63
9. No gross abnormalities in the ovaries62,63
10. No need for postoperative radiation57,58,62,63
f. Non-metastatic Exploratory laparotomy (EL), BSO and appropriate surgical
adnexal masses procedures as indicated, before chemoradiation
Option: Laparoscopy
g. Primary cases with Urinary diversion and/or stenting followed by primary treatment10
urinary obstruction
h. Primary cases with Medical or surgical decompression followed by primary
gut obstruction treatment
i. Hemato-/hydro-/ Drainage by cervical dilatation or EHBSO
pyometra (post RT)
j. Connective tissue Patients should be seen by the Multidisciplinary Team, which
disease (All stages should ideally include a rheumatologist.
requiring RT ) Ideally, patients disease should not be active at the time of
radiotherapy.
PERSISTENT OR RECURRENT DISEASE

PELVIC
With prior surgery, no prior radiotherapy Chemoradiation 1,65 [ Level 2A]
With prior radiotherapy, central disease with tumor Appropriate surgery (Type I or II extended
size 2 cm hysterectomy) may be performed 1,66 [Level C] (if
adverse surgico-prognostic factors are present,
adjuvant chemotherapy should be instituted)
With prior radiotherapy, central disease with tumor Platinum-based chemotherapy or best supportive
size > 2 cm and noncentral disease care 1,44
With prior chemoradiation, central disease with Nonplatinum-based chemotherapy or best
tumor size >2 cm and non-central disease supportive care 1,44
EXTRAPELVIC OR PARAAORTIC
Multiple sites, unresectable Systemic chemotherapy or best supportive care
1,44,67 [ Level 2A]
Isolated site Tumor resection 44[ Level 2A]
Tumor directed radiotherapy 44[ Level 2A]
Systemic chemotherapy or best supportive care
1,44,67 [ Level 2A]

Notes:
1. Chemotherapy may be given for palliative intent or symptomatic care. Chemotherapeutic options include:
SINGLE AGENT 1,44,68,69
a. Cisplatin [Level 1B] 50mg/m2 every 3weeks
b. Carboplatin [Level 1B]-50 mg/m2 every 3 weeks or 400mg/m2 every 3 weeks
c. Topotecan [Level 1B]-1.5mg/m2 days 1-5 every 4 weeks
d. Paclitaxel [Level 1B]- 170 mg/m2 for 24 hours every 3 weeks
COMBINATION CHEMOTHERAPY 1,44,68,69

a. Cisplatin Topotecan [Level 1B]- GOG 179 Cis 50 mg/m2 day 1, Topo 0.75 mg/m2 days 1-3 every
3 weeks
b. Cisplatin Paclitaxel [Level 1B]- GOG 169 Cis 50 mg/m2 day 1, Pacli 135 mg/m2 24 hours 3 weeks
c. Cisplatin-Ifosfamide [Level 1B] GOG 110 Cis 50 mg/m2 day 1, Ifos: 5 gm/m2/24 hours every 3
weeks
d. Cisplatin Gemcitabine [Level 2b] Cis 70 mg/m2 day 1, Gemcitabine 1.25 mg/m2 day 1, 8
every 3 weeks
e. Cisplatin- Irinotecan [Level 2b] Cis 50mg/m2, CPT-11 100mg/m2 every 3 weeks
f. Cisplatin Vinoralbine [Level 2b] Cis 75 mg/m2 Vin 30 mg/m2 every 4 weeks
g. Carboplatin-Paclitaxel [Level 2b] Carbo AUC 5-6 day pacli 155-175mg /m2 every 4 weeks
h. Topotecan-Paclitaxel [Level 2b] Pacli 175 mg/m2 day 1, topo 1 mg/m2 days 1-5 every 3 weeks
2. Combination regimens are preferred and are first line therapy if Cisplatin was previously used as a
radiosensitizer
3. Ongoing Trial GOG204-A Randomized Phase III Study of Paclitaxel plus Cisplatin Versus Vinorelbine Plus
Cisplatin Versus Gemcitabine Plus Cisplatin Versus Topotecan Plus Cisplatin in Stage IVB, Recurrent or
Persistent Carcinoma of the Cervix
FOLLOW UP
1. Weekly while on concurrent chemotherapy and radiotherapy.
2. Two (2) weeks post-completion of brachytherapy.
3. After completion of treatment, recommended follow-up is as follows:
a. Physical and pelvic exams every 3 months for the first 2 years, every 6 months from years 3-5, then yearly
thereafter.70
b. Pap smear every three months for the first 2 years, followed by pap smear every six months for the 3rd 5th
year, then annual pap smear thereafter.
NOTE: Perform colposcopy with appropriately guided biopsy and/or ECC, as warranted.
c. Chest x-ray annually or as indicated70.
d. An annual CT scan, MRI or PET scan for the first 3 years post-treatment is recommended, or when warranted.
4. Use of a vaginal dilator is suggested after radiotherapy for women who are sexually active 70Denton 2003 systematic review.
HORMONAL REPLACEMENT THERAPY (HRT) AFTER TREATMENT OF CERVICAL CANCER,
Hormone therapy may be given to symptomatic women who have been treated for cervical cancer.
1. HRT significantly reduced long term post radiation rectal, bladder and vaginal complications 71
2. There is no evidence that HRT increases risk of squamous cell carcinoma. For adenocarcinoma, a risk of recurrence
is noted in a descriptive study72.

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ENDOMETRIAL HYPERPLASIA1,2 (Review Articles)
For premenopausal women:

HISTOLOGIC TYPE MANAGEMENT
Hyperplasia without atypia 1. (for simple hyperplasia) OCP x 6 cycles
2. Medroxyprogesterone acetate (MPA) 10mg OD x 14 days
Do ultrasound and sample the endometrium after 3 months.
x IF NORMAL, continue MPA at 5 mg x 10 days/month for 12

months.
Note: Since there is no 5 mg MPA tab and it is also not
scored, give MPA 10 mg/tab for 10 days for 12 more months
x IF PERSISTENT, increase dose to 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
then do ultrasound and sample the endometrium
x IF NORMAL, decrease MPA to 10 mg OD x 14 days for 12

more months
x 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 (Review Article)
Then do endometrial sampling, if persistent, do hysterectomy
If not desirous of pregnancy, do hysterectomy
For postmenopausal women:

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

1. Levonorgestrel-releasing Intra-Uterine System (LNG-IUS)
2. Danazol 400 mg daily x 3 months
3. 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, the diagnosis should be confirmed by a hysteroscopy
or dilatation and curettage (D and C) for adequate exclusion of a concurrent endometrial malignancy.
2. Endometrial hyperplasia is a relative contraindication to endometrial ablation. It is paramount to exclude hyperplasia
or cancer before ablating the endometrium. 4 (Review Article)

ENDOMETRIAL CANCER
GENERAL GUIDELINES
1. Diagnosis is 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 (Review Article)
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 (Review Article)
Endocervical curettage (ECC) should be performed when radical hysterectomy for Stage II endometrial cancer
is being contemplated or when a patient is a candidate for conservative management (please see separate
entry on conservative management).
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.8 (Level 2b) There are also
no differences in recurrence rates and/or overall survival compared to the other diagnostic procedures.9 (Level
2b)
4. If cervical stenosis or patient tolerance does not permit an office procedure, then curettage under anesthesia is
necessary.10
5. Imaging studies like ultrasound can aid in the tailoring of management but not to be used as basis for
preoperative staging.
6. All patients should undergo the 1988 FIGO Surgical Staging after appropriate investigation and clearance.10
Laparoscopic-assisted vaginal hysterectomy (LAVH) in selected population (BMI < 35 kg/m2 uterine diameter <
10 cm, mobile uterus, no severe cardiopulmonary disease, no previous pelvic and abdominal radiation) with
clinical stage I and II endometrial adenocarcinoma appears to be a safe procedure.11 (Level 2b)
Laparoscopic-assisted surgery (LAVH + 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.12 (Level 1a)
Exceptions:
a. Patients who are poor surgical risk (morbid obesity, severe cardiopulmonary 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.10
b. Patients with far advanced 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. 10
c. Patients with a well-differentiated lesion and contraindications to general anesthesia and unsuited for
radiotherapy, high-dose progestins may be used.10
7. All specimens should be cut and examined immediately after removal to determine the further extent of surgery.

MANAGEMENT
There is a need to identify low risk, intermediate risk, and high risk patients. 13
Low risk:
Stage IA and IB, grade 1 and 2
Intermediate risk:
Stage IA and IB, grade 3
Stage IC and IIA, grade 1 and 2
Stage IIA, grade 3, but less than 50 % myometrial invasion
High risk:
Stage IC, grade 3
Stage IIA, grade 3 with more than 50 % myometrial invasion
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.
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.14 (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:10

1. suspicious para-aortic or common iliac nodes
2. grossly positive adnexa
3. grossly positive pelvic nodes
4. high grade tumors showing full thickness myometrial invasion
5. clear cell or papillary serous or carcinosarcoma
6. lower uterine segment involvement15 (Level 2b)
7. cervical involvement16 (Level 2b)
STAGE I: Confined to the Corpus

SURGERY: EHBSO, PFC, Lymph Node Evaluation
ADJUVANT: Radiation (not for low risk patients)17 (Level 1a)
SURGICO-PATHOLOGIC STAGING ADJUVANT TREATMENT
IA G1, G2 No adjuvant treatment18,19 (Level 2b)
G3 Vaginal brachytherapy20,21 (Level 2b)
IB G1, G2 No adjuvant treatment18,19 (Level 2b)
G3 Vaginal brachytherapy20,21 (Level 2b)

Or Pelvic EBRT22 (Level 1b)
IC G1,G2, G3 Pelvic EBRT17 (Level 1a)

Chemotherapy for early stage disease:
There is conflicting evidence for the use of chemotherapy for early stage endometrial carcinoma.23,24,25 (Level 1b, Level
2b, Level 1b). EORTC 55991, a randomized trial of adjuvant treatment with radiation plus chemotherapy versus radiation
alone in high risk Stage I endometrial carcinoma, is still ongoing.
Notes:
1. Routine omentectomy as part of surgical staging for seemingly early stage endometrioid type adenocarcinoma
is not recommended.26 (Level 2b)
2. Adjuvant treatment for adenocarcinoma with squamous differentiation will depend on the histological grade of
the glandular component.27
3. Lower uterine segment involvement is predictive of nodal spread for endometrioid histologic type tumors (odds
ratio:5)15 (Level 2b). The prognostic significance, however, remains unknown.
4. Positive LVSI regardless of stage and grade warrants adjuvant therapy since LVSI is a strong predictor of
distant and lymphatic recurrence28 (Level 2b) and is associated with a 2-fold risk of death.29 (Level 2b)
Adjuvant therapy is in the form of chemotherapy (doxorubicin-based)30,31 (Level 2b) OR pelvic external beam
radiotherapy.32 (Level 1b)
Another chemotherapeutic option is a Paclitaxel-containing regimen (consensus-based).
5. Results of PORTEC 2 (Phase III RCT) study comparing vaginal brachytherapy versus pelvic EBRT alone are
still pending.
STAGE II: Tumor extension to the cervix (Occult/Microscopic)

*Occult stage II is defined as (+) ECC with histologic continuity but with no gross evidence of cervical
involvement.
SURGICO- PRIMARY TREATMENT ADJUVANT TREATMENT
PATHOLOGIC
STAGING
IIA/IIB RHBSO, PFC, Lymph Node None33,34 (Level 2b)
Evaluation
EHBSO, PFC, Lymph Node Pelvic EBRT32 (Level 1b)
Evaluation
There is no apparent benefit for additional
brachytherapy 35 (Level 2b)
Note: RHBSO is the preferred surgical management especially if the oncologist could not ascertain immediate adjuvant
therapy due to lack of radiation facilities in the area.
STAGE II: Tumor extension to the cervix (Gross cervical involvement confirmed by biopsy)
*For good surgical risk patients
SURGICO-PATHOLOGIC PRIMARY TREATMENT ADJUVANT
STAGING TREATMENT
IIA/IIB G1,G2,G3 RHBSO, PFC, Lymph Node evaluation Observe33 (Level 2b)
STAGE II: Tumor extension to the cervix (Gross cervical involvement confirmed by biopsy)
*For poor surgical risk patients
1971 FIGO Clinical Stage II Pre-operative pelvic RT and vaginal brachytherapy
G1, G2, G3 followed by PFC & EHBSO with selective
lymphadenectomy (common iliac and para-aortic)10,36
(Level 4)

Notes:
1. For those patients who underwent RHBSO and whose lines of resection are negative, brachytherapy is not
necessary.
2. RH is the recommended surgical procedure for those with > 50% myometrial invasion + grade 3 tumors +
cervical involvement.
3. There is still a need to give adjuvant therapy if there is (+) LVSI (same as in Stage I)
STAGE III: Tumor extension outside the uterus, within the pelvis
SURGERY: EHBSO, PFC, Lymph Node Evaluation, Debulking
ADJUVANT CHEMOTHERAPY37 (Level 1A) followed by
ADJUVANT RADIATION38 (Level 2b)
SURGICO-PATHOLOGIC STAGING ADJUVANT TREATMENT*
IIIA (+) PFC with no other poor No adjuvant treatment39 (Level 2b)
prognostic factors
IIIA, (+) PFC, with other poor Chemotherapy (recurrence patterns* suggest
prognostic factors that systemic therapies are appropriate)40
Followed by Pelvic EBRT
IIIA (+) uterine serosa/adnexal G1,G2, G3 Chemotherapy followed by Pelvic EBRT
metastasis
IIIB G1,G2, G3 Chemotherapy followed by Pelvic EBRT +

vaginal brachytherapy
IIIC G1,G2, G3 Chemotherapy followed by EFRT** + vaginal

brachytherapy
*recurrence pattern extrapelvic

**EFRT extended field radiation therapy includes external pelvic and para-aortic radiation
Notes:
1. Current evidence does not support the use of adjuvant progestin therapy in the primary treatment of
endometrial cancer. 41,42 (Level 1a, Level 1b)
2. The chemotherapeutic options are as follows:
a. TAP Regimen43 (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 5ug/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.
Note: Toxicities of the regimen limit its clinical use.
b. AP Regimen44 (Level 1b)

Day 1: 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.
c. Carboplatin-Paclitaxel Regimen45 (Level 2b)

Carboplatin (AUC of 5-7) + Paclitaxel 175 mg/m2 (3-hr infusion) every 3 weeks for 6 cycles

d. Cisplatin Paclitaxel Regimen with RT24 (Level 2b)
D1 and 28: Cisplatin 50mg/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 cyles46
(Level 2b) (Phase II study)
3. The results of GOG 209 comparing Cisplatin-Doxorubin-Paclitaxel with Filgrastim and Carboplatin-Paclitaxel for
advanced stage disease are being awaited.
STAGE IV: Tumor invades bladder and/or bowel mucosa, +/- distant metastasis
SURGERY: EHBSO, Debulking
ADJUVANT CHEMOTHERAPY37 (Level 1a) followed by ADJUVANT RADIATION38 (Level 2b)
SURGICO-PATHOLOGIC PRIMARY TREATMENT ADJUVANT TREATMENT
STAGING
IV G1,G2, G3 EHBSO, Debulking Chemotherapy* followed by EFRT +
vaginal brachytherapy38 (Level 2b)
*chemotherapy regimens 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 size, site and bulk of metastatic lesions.
POOR HISTOLOGIC TYPES: UTERINE PAPILLARY SEROUS/CLEAR CELL CARCINOMA

SURGERY: EHBSO, IO, PFC, BLND, PALS, RPB
SURGICO-PATHOLOGIC PRIMARY TREATMENT ADJUVANT TREATMENT
STAGING
IA EHBSO, IO, PFC, BLND, Observation47,48 (Review Article,
PALS, RPB (Extended Level 2b)
Surgical Staging)47 (Review
Article)
IB-IV EHBSO, IO, PFC, BLND, Chemotherapy* followed by
PALS, RPB (Extended Abdominopelvic RT49 (Level 2b)
Surgical Staging)47 (Review
Article)
*Chemotherapy: Carboplatin (AUC 6) - Paclitaxel (175 mg/m2)
FINAL HISTOPATHOLOGY REPORT OF ENDOMETRIAL CANCER SPECIMENS

(2005 Consensus with the Philippine Society of Pathologists)
1. Histologic type
2. Histologic grade
3. LVSI
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

PERSISTENT OR RECURRENT DISEASE10,43,44,45
1. Treatment for patients with persistent or recurrent disease must be individualized.
2. Treatment will depend on site, extent of disease, and receptor status.
3. For localized recurrences (pelvis and para-aortic lymph nodes) or distant metastasis in selected sites: may give
irradiation.
4. Chemotherapy used for stage III/IV may be given.
5. 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%)46 (Level 2b)
b. Liposomal doxorubicin 40 mg/m2 every 4 weeks until toxicity or progression (36%)50 (Level 2b)
c. Weekly Paclitaxel 80 mg/m2 1 hour infusion until with response (26.7%)51 (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%)52 (Level 2b)
SPECIAL SITUATIONS
1. INADEQUATELY STAGED PATIENTS
Recommended Management of Patients with Endometrial Carcinoma Diagnosed on the Postoperative

Hysterectomy Specimen
a. For patients who underwent total hysterectomy alone:

SURGICO-PATHOLOGIC RESULT ADJUVANT TREATMENT
G1,G2 2 options:
< 50% myometrial invasion 1. re-operate and remove adnexa and perform
no LVSI surgical staging and give adjuvant treatment
< 2 cm28 accordingly
2. No further treatment/close observation53,54
(Level 2b)
G3 Pelvic EBRT
> 50% myometrial invasion
> 2 cm28
No LVSI
No evidence of metastasis
All others Re-operate to remove adnexa and perform surgical
(+) LVSI55 staging and give adjuvant treatment accordingly
(+) evidence of metastasis
Note: If a supracervical/subtotal hysterectomy was done, re-operation to remove the cervix and adnexa is
recommended.
b. For patients who underwent THBSO:22

SURGICO-PATHOLOGIC RESULT ADJUVANT TREATMENT
Confined to the Endometrium G1,G2 None
(Stage IA) G3 Vaginal brachytherapy20
Myometrial Invasion < 50% G1,G2 None22 (Level 1b)
(Stage IB) G3 Pelvic EBRT22 (Level 1b)

> 50% Myometrial Invasion G1,G2, G3 Pelvic EBRT22 (Level 1b)
(Stage IC)
Cervical involvement G1,G2, G3 Pelvic EBRT
(Stage II)
Uterine Serosa and/or Adnexal G1,G2, G3 Chemotherapy followed by Pelvic
involvement EBRT
(Stage IIIA)
Positive LVSI55 G1, G2, G3 Re-operate for lymphadenectomy
x If lymph node is (+), for
chemotherapy followed by EFRT
x If lymph node is (-), for pelvic
EBRT
OR
Give adjuvant therapy
2. ENDOMETRIAL CANCER IN PATIENTS LESS THAN 40 YEARS OLD56,57,58,59 (Review Articles)
a. If conservative treatment is contemplated, pre-treatment evaluation must be employed

x History and physical exam
Comprehensive physical & gynecologic exam
Fertility history of both patient and spouse
Family history
x Endometrial and endocervical 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 to 25 % of cases.3
(Review Article)
x Pathology review
x Imaging with contrast-enhanced MRI60 (Level 1a)
MRI provided the highest diagnostic accuracy (85-91%) for determining myometrial invasion.
Studies using ultrasound with Doppler have conflicting results regarding determination of
myometrial invasion.61,62,63,64,65 (Level 2b)
In smaller scale studies, PET scan has also shown usefulness in predicting myometrial
invasion in endometrial cancer.66 (Level 2b)
x Tumor marker: CA-125
x When previously performed diagnostics are inconclusive, laparoscopy can be done to inspect the
adnexae, get samples for peritoneal fluid cytology, and possible pelvic lymph node sampling.
x Molecular markers (progestin receptors)
b. Conservative treatment is only offered to patients who have:

x Well differentiated tumor (endometrioid type)
x No or minimal myometrial invasion
x No cervical involvement
x Negative PFC
x No evidence of lymph node metastasis
x No LVSI
x No adnexal involvement

The following are also essential:
x Progestin receptor positivity
x Careful, thorough, informed consent Inform patients that the procedure of preservation of fertility
is still experimental and there is low pregnancy rate.
x Patient with strong desire to preserve her childbearing potential
c. Agents used:
x Megestrol acetate 40 -160 mg/day Duration of treatment is
x Medroxyprogesterone acetate 100 - 800mg/day variable.
Other agents used:

x Tamoxifen + progestins
x Anastrozole + progestins
x LNG-IUS
d. Monitoring
Patients are followed up with a repeat D & C after 3 months of therapy. No response after 3 months of
therapy means treatment failure.
With reversion of the cancer, maintenance treatment with OCPs, cyclic progestins, DMPA, or LNG-IUS
must be given until pregnancy is desired.
If pregnancy is desired, attempts should be made within 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 (Review Article)
2. Ideally, an annual MRI or CT scan for the first three years post-treatment should be requested.
Ultrasonography with or without Color Doppler studies is an option.
3. Annual chest x-ray does not contribute to early detection of recurrences.6,67,68 (Review Articles, Level 2b)
4. 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.68,69 (Review
Article)
5. CA-125 monitoring is recommended in cases with advanced surgical stage (Stages III-IV) or high risk histologic
subtypes every 6 months on the first year and annually thereafter up to 5 years.67 (Level 2b)
HRT AFTER TREATMENT OF ENDOMETRIAL CANCER,
Hormone therapy may be given to symptomatic women who have been treated for endometrial cancer.70,71 (Review
Articles)
The absolute recurrence rate of Stage I and II endometrial cancer with hormone therapy use is 2.1% and the incidence
of a new malignancy is low.72 (Level 1b)

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UTERINE SARCOMAS
GENERAL GUIDELINE
Staging will follow the 1988 FIGO surgical staging for endometrial cancer.1
MANAGEMENT
A. Malignant Mixed Mullerian Tumor

STAGE Primary Treatment Adjuvant Treatment
I and II EHBSO, PFC, Pelvic RT to include upper half of the vagina4
Lymphadenectomy, IO, (Level 1b)
peritoneal biopsy2,3 (Review OR
Article, Level 2b) Cisplatin 20 mg/m2 (over 15 mins) -Ifosfamide
1.5 g/m2 (over 1 hr)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 (for 3 days) + Paclitaxel
Lymphadenectomy, IO, 135 mg/m2 (3 hour infusion on day 1) +
peritoneal biopsy2,3 (Review Filgrastim support7 (Level 2b)
Article, Level 2b)
Can follow this with pelvic EBRT8 (Level 2b)
Other options for chemotherapy:

1. Carboplatin AUC 5-6, Paclitaxel 175 mg/m2
(for 3 h every 4 weeks x 3-6 cycles)9 (Level
2b)
2. Ifosfamide-Doxorubicin10 (Level 2b)
3. Cisplatin (60-80 mg/m2) - Ifosfamide (1.2-
1.5 g/m2)11 (Level 2b)
PERSISTENT/RECURRENT DISEASE
Same as for stage III/IV diseases
B. Leiomyosarcoma
I and II EH Doxorubicin 60 mg/m2 every 3 weeks
(BSO*, LND not (maximum of 480 mg/m2)14 (Level 1b) -
mandatory)2,12,13 (Review results favor only LMS but no difference in
Articles, Level 2b) PFS and survival
With15,16 (Level 2b) or without4 (Level 1a)

subsequent Pelvic EBRT and vaginal
brachytherapy

III and IV EH Doxorubicin 60mg/m2 to a maximum of 480
(BSO*, LND not mg/m17,18 (Level 1b, Level 2b)
mandatory)2,12,13 (Review OR
Articles, Level 2b) Ifosfamide plus Doxorubicin19 (Level 2b)
* BSO is not mandatory if the ovaries are not grossly involved and if the patient is young.
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)
C. Endometrial Stromal Sarcoma

I and II EHBSO,PFC,Pelvic/Peri-aortic Pelvic EBRT16,22 (Level 2b)
LN Dissection/ Assessment 2,12
(Review Article, Level 2b) If high-grade, chemotherapy with:
Ifosfamide (1 g) Epirubicin (25 mg/m2)
Cisplatin (20 mg) or Vincristine (1.2 mg/m2)
Doxorubicin (20 mg/m2) Dacarbazine (250
mg/m2)23 (Level 4)
III and IV EHBSO,PFC,Pelvic/Peri-aortic Ifosfamide 1.5 g/m2 x 5 days every 3 weeks

LN Dissection/ Assessment2,12 for 6-8 courses plus Mesna24 (Level 2b)
(Review Article, Level 2b)
Followed by pelvic EBRT16,22 (Level 2b)
Notes:
1. For low-grade ESS, hormonal therapy may be given as adjuvant treatment (progestins, aromatase
inhibitors, GnRH analogues)25,26 (Review Article)
2. Progestins can be in the form of megestrol acetate 160 mg/day for 24 months.27 (Review Article)
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:

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.
Note: Perform colposcopy with colpo-guided biopsy, if indicated, for abnormal cytology results.
c. Chest x-ray every 6 months (more often if symptomatic).
d. An annual CT Scan or MRI for the first three years post-treatment is recommended.

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OVARIAN CANCER
GENERAL GUIDELINES
1. Ovarian cancer is surgically staged (Appendix C.III).1

2. Ideally, there should be histologic confirmation of the disease.1
3. Pre-operative work-ups should include chest x-ray, abdominopelvic CT scan or MRI with contrast, tumor markers, and
barium enema if indicated. For patients with pleural effusion with negative cytology and no evidence of pulmonary
metastasis on x-ray, chest CT scan is recommended. 2
4. Pleural effusion should be aspirated for cytology.
5. Guidelines for the complete surgical staging of ovarian 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 1A
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.3,4,5
j) For mucinous tumors or other types of ovarian tumors with the appendix grossly involved with tumor,
appendectomy must be performed. 1,6,7 (Level 3b)
MANAGEMENT
I. EPITHELIAL OVARIAN TUMORS OF LOW MALIGNANT POTENTIAL (Atypically Proliferating Tumors)
STAGE STATUS INTERVENTION 6,7 (Level 2b) ADJUVANT THERAPY

Young/desirous of pregnancy USO/BSO, IO, PFC, complete surgical staging None*
IA IB
Reproductive function not desired THBSO, IO, PFC, complete surgical staging None*
Optimally debulked (residual tumor
Chemotherapy
IC IV < 2.0 cm) or Sub-optimally THBSO, IO, PFC tumor debulking
(Consensus-based)
debulked (residual tumor t 2.0cm)
SPECIAL CLINICAL SITUATION
Do diagnostic imaging (CT Scan / MRI)

o No residual disease surveillance
o (+) gross disease OPTIONS: Need for adjuvant therapy will depend on
Inadequately Staged Tumors
1. Re-explore & do tumor debulking final surgico-pathologic stage
(preferred option) OR
2. Interval Debulking Surgery (IDS)

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.1,
10 (Level 2b)
2. 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. 11, 12
II. FRANKLY MALIGNANT EPITHELIAL OVARIAN CARCINOMAS (EOC)
STAGE STATUS INTERVENTION ADJUVANT THERAPY

IA - IB Young/desirous of pregnancy IA USO, IO, PFC, complete surgical staging
(G1, G2) IB BSO, IO, PFC, complete surgical staging None 11,12,13 (Level 1a)
Reproductive function not desired THBSO, IO, PFC, complete staging
IA - IB Optimally debulked THBSO, IO, PFC, Complete surgical staging Chemotherapy*
(G3)
Chemotherapy* followed by
Sub-optimally debulked THBSO, IO, PFC, Complete surgical staging
IC III IDS**
Chemotherapy* 16
IV Optimally or Sub-optimally debulked THBSO, IO, Tumor Debulking
(Level 2b)
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. 11,12
SPECIAL CLINICAL SITUATIONS
Options for Early Stages: Options for Advanced Stages:

A. Inadequately 1. Re-explore and surgically stage 1. Re-explore and do debulking surgery, followed by
Staged Tumors 2. Chemotherapy* (Level 1b) chemotherapy*
2. Chemotherapy*, followed by IDS**15,25, 26 (Level 1b)
1. Conservative surgery (USO, IO, PFC, complete surgical staging) is standard for early stage.23
2. Conservative surgery, followed by antepartal chemotherapy (Cisplatin-Cyclophosphamide) 24 for
B. Ovarian Cancer
advanced disease beyond second trimester (Level 4)
in Pregnancy
3. Completion surgery post-partum for advanced diseases or for early stages not desirous of
pregnancy
*Chemotherapeutic Regimens Recommended for EOC:
1. Paclitaxel 175 mg/m2 + Carboplatin AUC 5-7 every 21 days for 6 cycles 17,18 (Level 1b)
2. Docetaxel 75 mg/m2 + Carboplatin AUC 5-7 every 21 days for 6 cycles19 (Level 1b)
3. Carboplatin AUC 5 (minimum) every 21 days for 6 cycles 20,21 (Level 1b)
4. Cisplatin 75 mg/m2 + Cyclophosphamide 750 mg/m2 every 21 days for 6 cycles 22 (Level 1a)
** Interval debulking surgery (IDS) may be considered after 2-4 cycles of systemic chemotherapy. 15, 25, 26 (Level 1b)

Notes:
1. Intraperitoneal chemotherapy is an option for advanced epithelial ovarian cancers which were optimally
debulked 27 (Level 1A).
2. 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 cystadenocarcinoma, pelvic residual disease 2.0 cm, abdominal residual 1.0 cm, or for
patients who are not good candidates for chemotherapy. 28,29
3. For stage IA diseases which were completely surgically staged but with (+) LVSI, is there a need for adjuvant
therapy? (No evidence on literature search but text survey among SGOP members showed an overwhelming
preference for adjuvant chemotherapy CONSENSUS-BASED).
PERSISTENT OR RECURRENT DISEASE
1. Taxane (Paclitaxel 175 mg/m2)+ Carboplatin AUC 5-6 every 21 days for 6 cycles 2,10
(Level 1b)
2. Single agent Carboplatin AUC 5-7 or Cisplatin 75 mg/m2 every 21 days for 6 cycles
Platinum Sensitive 1, 31 ( Level 1b)
(disease-free interval 6 months) 3. Gemcitabine 1000 mg/m2 on D1 and D8 + Carboplatin AUC 5 every 21 days for 6
cycles 32 ( Level 1b)
4. Pegylated Liposomal Doxorubicin 30 mg/m2 + Carboplatin AUC 5 every 28 days x 6
cycles 33 (Level 2b)
1. Oral Etoposide 50-100 mg OD for 21days every 28 days until disease progression
or toxicity occurs 36,37 ( Level 2b)
2. Taxanes (Paclitaxel )80-90 mg/m2 D1, D8, D15 every 28 days until tumor
progression or toxicitiy occurs 34 ( Level 2b)
3. Liposomal Doxorubicin 40-50 mg/m2 every 28 days for 6 cycles 35, 43 ( Level 1b)
4. Topotecan 1.0-1.5 mg/m2 D15 every 21 days for 8 cycles 35 ( Level 1b)
5. Tamoxifen 20 mg BID daily until disease progression or toxicity occurs 40 ( Level 1a)
Platinum Refractory
6. Gemcitabine 800-1000 mg/m2 on D1, D8, D15 every 28 days or
(disease-free interval < 6months)
800- 1000 mg/m2 on D1, D8, every 21 days until tumor progression or
toxicity occurs 38,39 ( Level 2b)
7. Capecitabine 1,500-2,000 mg/m2 daily in 2 divided doses for 2 weeks every
21 days until tumor progression or toxicity occurs 41 ( Level 2b)
8. Vinorelbine 30 mg/m2 on D1 and D8 every 21 days for 4 to 8 weeks 42( Level 2b)
9. Bevacizumab 15 mg/kg IV every 21 days until tumor progression or toxicity
occurs 44 (Level 2b)
RECOMMENDATIONS FOR MANAGING RISING CA 125 IN ASYMPTOMATIC PATIENTS
x CA 125 determination every 2-3 months during follow-up post-chemotherapy 45
x Definitions of CA 125 progression:

1. an increase of 50%, 100% or to just above the normal range ,46, 47, 48
2. increase of CA 125 > 2x the upper limit of normal 49
3. doubling of CA 125 from its nadir level 50
4. an absolute increase of 10 U/ml within the normal range, or a relative increase of 100%
compared to baseline nadir 51
5. GCIG definition of Progression based on both clinical and/or CA-125 criteria: 52

CRITERIA GROUP A GROUP B GROUP C
CA-125 - CA 125 elevated pre- - CA 125 elevated pre- - CA 125 in normal
treatment but later treatment and does not range pretreatment
normalizes normalize - as for group A
- CA 125 >/= 2x ULN - CA 125 >/= nadir
documented on 2 value on 2 occasions*
occasions *
- date of Progressive
- date of Progressive Disease: first date of the
Disease: first date of CA CA-125 elevation to >/=
125 elevation to >/= 2x 2x nadir value
ULN
* repeat CA-125 anytime, but normally not less than 1 week after the first elevated level. CA-125 sampled after
administration of mouse antibodies or within 4 weeks after surgery or paracentesis should not be taken into account.
x Work-ups:
- if a rise in CA-125 is confirmed, an abdominopelvic CT scan 53,54 or MRI 53 should be requested.
- CXR or chest CT scan is generally reserved for patients with elevated CA-125 with no evidence
of abdominopelvic disease. 55
- FDG-PET is indicated when conventional imaging is inconclusive or negative.55,56
x Option to either closely observe or immediate therapy for patients with rising CA-125 levels with negative
diagnostic work ups.57
x Survival advantage of early reintroduction of treatment is unclear. Until the results of the The Medical
Research Council (OV05)/ EORTC (55955) trial comparing early treatment based on CA-125 versus delayed
treatment based on clinical indicators are available, there is no proven benefit of early treatment. 50,54
III. GERM CELL TUMORS (GCT)

For all tumors other than pure
Young/desirous of pregnancy USO*, IO, PFC, complete staging
dysgerminoma and low-grade (grade I)
IA, G1
immature teratoma, chemotherapy is
given55 (Level 3a)
USO*, IO, PFC, complete staging
Young/desirous of pregnancy
IA G2,G3 tumor debulking 1. Chemotherapy**
II III THBSO, IO, PFC, complete staging 2. EBRT for Dysgerminoma
Reproductive function not desired
tumor debulking
Young/desirous of pregnancy USO*, IO Tumor Debulking
IV Chemotherapy** 56 (Level 2b)
Reproductive function not desired THBSO, PO Tumor Debulking
Note: For patients whose contralateral ovary appears grossly enlarged, bisection and frozen section should be done to
look for foci of germ cell tumor. Wedge biopsy of a grossly normal-looking ovary is not recommended.1

1. Re-explore and surgically stage

A. Inadequately Staged Tumors 2. Chemotherapy**
3. Radiation Therapy for dysgerminoma
1. Conservative surgery (USO, IO, PFC, complete surgical staging) is standard for early
stage.24
2. Conservative surgery, followed by antepartal chemotherapy** (BEP) 24 for advanced
B. Ovarian Cancer in Pregnancy
disease beyond second trimester (Level 4)
3. Completion surgery post-partum 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
cycles 1, 58 (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 350 ug/m2 D1-5 every 28days +
Cyclophosphamide 150 mg/m2 D1-5 every 28 days for 6 cycles 59
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 1
4. CAP Regimen: Cisplatin 50 mg/m2 + Adriamycin 50 mg/m2 + Cyclophophamide 500 mg/m2 every 21 days for 6 cycles 1
5. Vinblastine 0.11 mg/kg D1-2 + Ifosfamide 1.2 g/m2 D1-5 + Cisplatin 20 mg/m2 D1-5 for 4 cycles 1
Chemotherapeutic Regimens for Recurrent Dysgerminoma 61

1. Cisplatin with or without Radiation Therapy
Chemotherapeutic Regimens for Recurrent Non-Dysgerminoma Tumors 61

1. 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
cycles1
Cyclophosphamide 150 mg/m2 D1-5 every 28 days for 6 cycles
IV. SEX CORD STROMAL TUMORS (SCST)
IA Young/desirous of pregnancy USO, IO, PFC, complete surgical staging

None,,13,14,15 (Level 1a)
1. Chemotherapy* (optional)
IB II Optimally or Sub-optimally debulked THBSO, IO, PFC, Complete surgical staging
2. Pelvic EBRT
1. Chemotherapy*
III IV Optimally or Sub-optimally debulked THBSO, IO Tumor Debulking
2. WART
A. Inadequately 1. Re-explore and surgically stage

Staged Tumors 2. Chemotherapy*

1. Conservative surgery (USO, IO, PFC, complete surgical staging) is standard for early stage.24
2. Conservative surgery, followed by antepartal chemotherapy* for advanced disease beyond second
B. Ovarian Cancer
trimester
in Pregnancy
3. For advanced stage, completion surgery post-partum 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 days 1, 60
(Level 2b)
Cyclophosphamide 150 mg/m2 D1-5 every 28 days for 6 cycles 59
3. CAP Regimen: Cisplatin 50 mg/m2 + Adriamycin 50 mg/m2 + Cyclophophamide 500 mg/m2 every 21 days for 6 cycles 1
4. Carboplatin AUC 5 Paclitaxel 175 mg/m2 every 21 days for 6 cycles 62,63
FINAL HISTOPATHOLOGY REPORT OF OVARIAN CANCER SPECIMENS

1. Histologic Type
2. Histologic Grade (especially for mucinous tumors and immature teratoma)
3. LVSI
4. Omentum
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 64
1. 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 r color Doppler studies every 4-6 months
d. CXR if indicated by signs or symptoms (not routine)
d. An annual MRI or CT scan for the first 3 years post-treatment is recommended, or when indicated.
e. Follow-up of patients with LMP may be at less frequent intervals.
HRT AFTER TREATMENT OF OVARIAN CANCER,
1. Hormone therapy may be given to symptomatic women who have been treated for ovarian cancer. 65
2. For EOC in close association with endometriosis (i.e. endometrioid & clear cell carcinomas), request for estrogen-
progesterone receptor (ER/PR) assays. If ER/PR negative, hormone therapy may be given immediately for symptomatic
women. However, if ER/PR positive, hormone therapy must be deferred until after 5 years without evidence of disease.
Combined estrogen-progestin regimen is the recommended hormone therapy. 66

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50. Rustin GJS, Marples, M, Nelstrop AE et al. Use of CA 125 to define progression of ovarian cancer in patients
with persistently elevated levels. J Clin Oncol 19:4054-4057, 2001.
51. Santillan A, Garg R, Zahurak ML, et al. Risk of epithelial ovarian cancer recurrence in patients with rising CA
125 levels within normal range. J Clin Oncol 2005; 23: 9338-43.
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ovarian cancer in the intergroup trial of cisplatin and paclitaxel versus cisplatin and cyclophosphamide.
53. Gadducci A, Cosio S, Zola P, et al. Surveillance procedures for patients treated for epithelial ovarian cancer: a
review of literature. Int J Gynecol Cancer 2007, 17, 21-31.
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with rising CA-125 concentrations. Lancet Oncol 2007; 8:813-21.
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FALLOPIAN TUBE CANCER

GENERAL GUIDELINES
1. Fallopian tube cancer is surgically staged (Appendix C.IV).1

2. There should be histologic confirmation of the disease.1
3. Pre-operative work-ups should include chest x-ray, abdominopelvic CT scan or 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 1A
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
MANAGEMENT
IA G1 Young/desirous of pregnancy USO, IO, PFC, complete surgical staging 1,2

None
Optimally debulked THBSO, IO, PFC, Complete surgical staging Chemotherapy*

IA G2 -
IV Chemotherapy* followed by
Sub-optimally debulked THBSO, IO Tumor Debulking
IDS
*NOTE: Chemotherapeutic options, the timing of 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 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 edge1) 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 CT Scan or MRI of the pelvis and groins is often helpful to detect any enlarged lymph nodes in the groins and
pelvis.3 Frozen section of clinically suspicious inguinal lymph nodes 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 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
Comparison of the International Society for the Study of Vulvovaginal Disease (ISSVD) 1986 and 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.
x VIN usual type is the 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.
x 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 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

VIN usual and OPTIONS:6 (Level 2b) None
differentiated 1. Superficial excision
types and 2. CO2 Laser
Carcinoma- 3. Skinning vulvectomy
in-situ 4. 5% Fluorouracil cream
(Stage 0) 5. Imiquimod7,8
MANAGEMENT OF EARLY PRIMARY TUMOR (Stage IA-II)

NODES CLINICALLY NEGATIVE (Level 2b)
TREATMENT
Lesion >2 cm x Radical local excision with bilateral inguino-femoral lymphadenectomy
Lesion 2 cm
- If stromal invasion >1mm x Radical local excision with unilateral inguino-femoral lymphadenectomy
unless if:
1. Within 1 cm of midline
2. Labia minora involved
3. Ipsilateral positive nodes
x Otherwise, Radical local excision with bilateral inguino-femoral
lymphadenectomy*
- If stromal invasion 1mm x Complete excision of the lesion to allow serial sectioning and proper
assessment of depth of invasion
x > 1mm invasion - Manage as above
x 1mm invasion Radical local excision
*Triple incision technique to decrease morbidity
ADJUVANT TREATMENT FOR EARLY PRIMARY TUMOR WITH POOR PROGNOSTIC FACTORS
POOR PROGNOSTIC FACTORS ADJUVANT TREATMENT

LYMPH NODE STATUS Pelvic and bilateral inguinal radiotherapy
1. Macrometastasis (>5mm)
2. Extracapsular spread
3. >2 nodes with micrometastasis (<5mm)
PRIMARY TUMOR Pelvic, vulvar and bilateral inguinal radiotherapy

1. (+) lines of resection
2. surgical margins <8mm
3. capillary lymphatic space invasion
MANAGEMENT OF ADVANCED PRIMARY TUMOR (Stage III-IV) (Level 2b)

I. GROIN NODE
(It is advisable to determine groin node status before definitive management of primary lesion. Pre-operative CT scan
may help identify extent of groin and pelvic lymphadenopathy.)
LYMPH NODE STATUS PRIMARY TREATMENT ADJUVANT

No suspicious lymph nodes Bilateral inguino-femoral If histopath POSITIVE for:
palpable lymphadenectomy* 1. Macrometastasis (>5mm)
2. Extracapsular spread
3. >2 nodes with micrometastasis
(<5mm)
x Bilateral pelvic and inguinal
radiotherapy
If histopath NEGATIVE or only 1

microscopically positive node
x Observation
Suspicious groin nodes Resection of macroscopic groin

nodes followed by frozen section
If FS POSITIVE: x Bilateral pelvic and inguinal

x Resect any macroscopic radiotherapy
groin and pelvic nodes seen
on CT scan and defer
complete lymphadenectomy
If FS NEGATIVE: If definitive histopath is POSITIVE:

x Complete the inguino-femoral x Bilateral pelvic and inguinal
lymphadenectomy radiotherapy
If definitive histopath is NEGATIVE or 1

microscopically positive node:
x Observation
Fixed or ulcerated groin nodes If resectable:

x Resection of all macroscopic x Bilateral pelvic and inguinal
groin nodes and any radiotherapy
enlarged pelvic nodes on CT
scan
If unresectable:
x Preoperative radiotherapy + x Post-operative resection of
chemotherapy (Cisplatin + 5- macroscopic residual disease
FU or Carboplatin)42
Concurrent chemotherapy:

1. Cisplatin + 5-FU protocol
x Cisplatin 50 mg/m2 IV infusion over 1 mg/min on Days 1 and 21 of radiation therapy
x 5-FU 1000 mg/m2 per 24 h continuous IV infusion over 96 h on Days 25 and 2225 of radiation therapy
2. 5-FU + Mitomycin C protocol

x 5-FU 1000 mg/m2 per 24 h continuous IV infusion over 96 h on Days 1-4 and 21-24 of radiation therapy
x Mitomycin C 10 mg/m2 IV bolus on Days 1 and 21 of radiation therapy
II. PRIMARY LESION (Level 2b)
PRIMARY TREATMENT ADJUVANT

Tumor resectable without Radical tumor resection If margin positive or 8mm:
requiring stoma x Post-operative radiotherapy
If >8 mm:
x Observe
Resection would require stoma Pre-operative radiotherapy +

chemotherapy (more limited
resection of tumor bed)
TUMOR RECURRENCES
Local vulvar recurrence Options: (Level 3b)

1. Wide local excision with or without radiation in patients with small volume
recurrent tumor
2. Radical exenterative surgery
3. Chemoradiation
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.
FINAL HISTOPATHOLOGY REPORT OF VULVAR CANCER SPECIMENS

1. Histologic Type
2. Histologic Grade
3. 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 mm.
FOLLOW-UP

1. Weekly while on cobalt therapy.
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 colposcopy-guided biopsy, if indicated, for abnormal cytology results.
4. Ideally, an annual CT Scan for the first three years post-treatment should be requested.
5. Chest x-ray every 6 months for the first two (2) years then yearly thereafter.
VULVAR MELANOMA
CLARKS PRIMARY TREATMENT ADJUVANT

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

GENERAL GUIDELINES
1. Up to 1015% of cases of vulvar Pagets disease are associated with an underlying adenocarcinoma. Furthermore,
many patients diagnosed with PD 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
x Wide local excision with removal of underlying dermis, in the absence of clinical or histologic evidence of
invasive carcinoma. (Level 3b)
x Removal of a small amount of subcutaneous tissue to rule out an underlying occult adenocarcinoma.
x Frozen section 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 frozen section.
2. Extend surgical margins beyond the usual margins of the gross lesion.
3. If no frozen section, wait for final histopathology report of specimen and do re-excision if necessary.
4. Wait for recurrence to develop then re-excise, (the disease is slow-growing and is amenable to excision).
x 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
BARTHOLINS GLAND CARCINOMA
TREATMENT
Surgical management of Bartholins carcinoma is similar to that of squamous-cell carcinoma:
x Radical hemivulvectomy with ipsilateral groin node dissection for early lesions [primary tumor <2 cm] and does
not encroach upon the midline [>1 cm from the midline]. (Level 2b)
x Radical vulvectomy with bilateral groin node dissection for lesions >2 cm or encroaches on the midline. (Level
2b)
x Radical local excision for adenoid cystic lesions. (Level 2b)
If a tumor is deemed to be unresectable:

x Neoadjuvant chemoradiation followed by surgical resection [if the tumor becomes resectable after
chemoradiation]. (Level 2b)
Primary radiotherapy with or without concomitant chemotherapy [weekly Cisplatin] with or without boost to the
primary site, regional nodes and/or interstitial brachytherapy. (Level 3b)
ADJUVANT

Post operative radiation for:
x Positive or close margins
x Positive inguinal femoral lymph nodes
x Adenoid cystic lesions with positive margins or perineural invasion
BASAL CELL CARCINOMA OF THE VULVA
TREATMENT
x Wide local excision with at least 1 cm margin. (Level 3b)
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VAGINAL CANCER
GENERAL GUIDELINES

1. Vaginal cancer is diagnosed by biopsy and clinically staged.1
2. Due to proximity to other organs, diagnostic examinations to rule out adjacent organ (particularly, cervix and vulva)
primaries should be done.1
3. Colposcopy, cystoscopy, and proctosigmoidoscopy should be performed, if clinically indicated.
4. A complete systemic 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- TREATMENT
INVASIVE
VAIN I-III OPTIONS: 1, 5, 6, 10 (Level 3b)
1. Wide local excision (excisional procedures either with electrosurgical loops or scalpel incison)1
2. Brachytherapy to the entire vaginal mucosa.1,8
3. For multifocal/ extensive disease, partial or total vaginectomy with or without skin grafting10
4. CO2 laser therapy1, 5, 6
5. 5-FU cream 1, 6
6. 5% Imiquimod cream13
II. Malignant Disease
STAGE TREATMENT OPTIONS

0 Same treatment options used for VAIN 1, 5, 6, 10 (Level 3b)
STAGE SIZE TREATMENT OPTIONS ADJUVANT THERAPY
I < 0.5cm Options : (Level 2b) For those who underwent
thick 1. Wide local excision or total vaginectomy with primary surgery, if with <1cm or
vaginal reconstruction3 positive surgical margin:
2. Brachytherapy 2 Interstitial or vaginal
3. Complete RT with inguinal boost2 brachytherapy
> 0.5 cm 1. Interstitial or intracavitary radiotherapy with For those who underwent
thick EBRT 2,16 primary surgery, if with <1cm or
2. Radical hysterectomy with pelvic positive surgical margin:
lymphadenectomy for lesions of the upper Interstitial or vaginal
posterior third of the vagina1, 5,10 brachytherapy
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
vulva 2
4. For poorly differentiated tumors:Complete RT +/-
inguinal EBRT2,16
STAGE TREATMENT OPTIONS

II 1. For small lesions ( 5cm), interstitial or intracavitary brachytherapy
For larger lesions, pelvic EBRT followed by interstitial or intracavitary brachytherapy 1,14
2. Concurrent chemoradiation with Cisplatin 15 (Level 3b)
3. Chemoradiation with 5-FU with or without cisplatin or mitomycin4
4. Radical surgery (radical vaginectomy or pelvic exenteration) with or without RT 3, 10, 11
III- IVA 1. Radiotherapy: EBRT + interstitial and/or intracavitary brachytherapy2

2. Concurrent chemoradiation with Cisplatin 15 (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 mitomycin plus additional dose to the
Persistent/ lateral pelvic wall4
Recurrent 2. Pelvic exenteration1
FINAL HISTOPATHOLOGY REPORT OF VAGINAL CANCER SPECIMENS

1. Histologic Type
2. Histologic Grade
3. LVSI
4. If surgical treatment is performed, state status of margins.
5. If RH performed, follow same recommendations for final histopathology report for cervical cancer.
FOLLOW-UP
1. Weekly while on cobalt therapy.

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 for the first three years post-treatment should be requested.
5. Annual chest x ray
VAGINAL MELANOMA
CLARKS TREATMENT
LEVEL
IV 1. Wide local excision 17,18
2. Radiation therapy using high-dose fractions 19
3. Pelvic exenteration
REFERENCES

1. Benedet JL, Pecorelli S, Ngan HYS, Hacker NF. Cancer of the Vagina. Staging classifications and clinical practice
guidelines of gynecologic cancers by FIGO Committee on Gynecologic Oncology and IGCS Guidelines Committee,
third edition: 26-35. November 2006.
2. Urbanski, K. Kojs, Z. Reinfuss, M. Fabisiak, W. Primary Invasive Vaginal Carcinoma Treated with Radiotherapy :
Analysis of Prognostic Factors. Gynecologic Oncology 1996; 60 :16-20.
3. Tjalma, W. Monaghan, J. Lopes, A. Naik, Raj. Nordin, A. Weyler, J. The Role of Surgery in Invasive Squamous
Carcinoma of the Vagina. Gynecologic Oncology. 2001; 81 : 360-365.
4. Dalrymple, J. Russell, A. Lee, S. Scudder, S. Leiserowitz, W. Kinneys W. Smith, L. Chemoradiation for Primary
Invasive Squamous Carcinoma of the Vagina. International Journal of Gynecologic Oncology 2004; 14: 110-117.
5. Creasman W. Vaginal Cancers. Current Opinion in Obstetrics and Gynecology 2005; 17: 71-76.
6. Krebs HB: Treatment of vaginal intraepithelial neoplasia with laser and topical 5-fluorouracil. Obstetrics and
Gynecology 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. International Journal of Radiation Oncology, Biology, Physics 1988; 15(6): 1283-1290.
8. Woodman CB, Mould JJ, Jordan JA: Radiotherapy in the management of vaginal intraepithelial neoplasia after
hysterectomy. British Journal of Obstetrics and Gynaecology 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, pp 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. Gynecologic Oncology 1995; 56(1): 45-52.
11. Rubin SC, Young J, Mikuta JJ: Squamous carcinoma of the vagina: treatment, complications, and long-term follow-
up.Gynecologic Oncology 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. American
Journal of Clinical Oncology 1987; 5 (2): 171-181.
13. Le T, Menard C, Hicks-Boucher W, Hopkins L, Weberpals J, Fung-Kee-Fung M: Final results of a phase 2 study
using continuous 5% Imiquimod cream application in the primary treatment of high grade vulva intraepithelial
neoplasia 2007; 106:579-584
14. Chyle V, Zagars G, Wheeler J. Definitive Radiotherapy for Carcinoma of the Vagina: Outcome and Prognostic
Factors. International Journal of Radiation Oncology, Biology and Physiology 1996; 35(5): 891-905.
15. Samant R, Lau B, Choan E, Le T, Tam T. Primary Vaginal Cancer Treated with Concurrent Chemoradiation using
Cisplatinum. International Journal of Radiation Oncology, Biology and Physics 2007; 69(3): 746-750.
16. Perez CA, Grigsby PW, Garipagaoglu M. Factors Affecting Long-Term Outcome of Irradiation in Carcinoma of the
Vagina. International Journal of Radiation Oncology, Biology and Physiology 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. American Journal of Obstetrics and Gynecology 1998; 178:912-917
19. Harwood AR, Cumming BJ. Radiotherapy for Mucosal Melanoma. International Journal of Radiation Oncology,
Biology and Physiology 1982;8:1121-1127
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
patients 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
* New NSAIDs: selective cyclooxygenase 2 inhibitors. At present, much of the clinical information on
the use of COX-2 antagonists is from rheumatology literature. More research is 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 NSAIDs rather than
acetaminophen.
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 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
patients 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
World Health Organization. Expert Committee Report 1990. Cancer Pain Relief and Palliative Care. Technical Series
804. Geneva: World Health Organization 1990
Foley,K. The Treatment of cancer pain. N Engl J Med 1985; 313-93.
Portenoy RK, Hagen, NA. Breakthrough pain: definition, prevalence and characteristics. Pain 1990;41; 273-281
Krames E. Med Clin North America. 1999;83: 787-808
PREVENTION AND TREATMENT OF COMPLICATIONS

I. GUIDELINES FOR THE USE OF ANTIEMETICS
DEFINITION
ACUTE Initial 24o after chemotherapy
DELAYED Later than 24o after chemotherapy
ANTICIPATORY Days to hours before chemotherapy, in patients who have had poor control of vomiting with prior
chemotherapy & history of motion sickness
OTHER CAUSES OF NAUSEA AND VOMITING TO BE CONSIDERED

1. Radiotherapy 8. Cachexia syndrome
2. Radiosensitizers 9. Metastases (brain, liver, bone)
3. Infection 10. Paraneoplasia
4. Metabolic disorders 11. Other emetogenic medications (opioids,
5. Electrolyte disturbances antibiotics, antifungals, amifostine)
6. Constipation 12. Psychologic
7. Gastrointestinal obstruction
A. CHEMOTHERAPY-INDUCED EMESIS
Single dose administered before Single dose administered daily

chemotherapy
HIGH EMETIC RISK (>90%)
Carmustine 5-HT3 serotonin receptor
Cisplatin antagonists:
Cyclophosphamide > 1,500 mg/m2 Dolasetron 100 mg PO or
Dacarbazine 100 mg IV or 1.8 mg/kg IV
Dactinomycin Granisetron 2 mg PO or 1 mg
Hexamethylmelamine (oral) IV or 0.01 mg/kg IV
Ondansetron 24 mg PO or 8
Mechlorethamine
mg IV or 0.15 mg/kg IV
Procarbazine (oral) Palonosetron 0.25 mg IV
Streptozotocin Tropisetron 5 mg PO or 5 mg
IV
+ Dexamethasone 12 mg PO or Dexamethasone 8 mg PO days
20 mg IV 2-4
+ Aprepitant 125 mg PO + Aprepitant 80 mg PO days 2-3
MODERATE EMETIC RISK (30-90%)
Carboplatin 5-HT3 serotonin receptor 5-HT3 serotonin receptor
Cyclophosphamide < 1,500 mg/m2 antagonists: antagonists
Cyclophosphamide (oral) Dolasetron 100 mg PO or 100
Cytarabine > 1 g/m2 mg IV or 1.8 mg/kg IV
Daunorubicin Granisetron 2 mg PO or 1 mg
Doxorubicin IV or 0.01 mg/kg IV
Ondansetron 16-24 mg PO or
Epirubicin
8 mg IV or 0.15 mg/kg IV
Etoposide (oral) Palonosetron 5 mg PO or 0.25
Idarubicin mg IV
Ifosfamide Tropisetron 5 mg PO or 5 mg
Imatinib (oral) IV

Irinotecan + Dexamethasone 8 mg IV (if OR Dexamethasone 8 mg PO
Oxaliplatin without Aprepitant) or 12 mg PO days 2-3
Temozolomide (oral) (if with Aprepitant)
Vinorelbine (oral)
No routine antiemetic for oral
chemotherapy after day 1
Combination of Anthracycline & + Aprepitant 125 mg PO Aprepitant 80 mg PO days 2-3

Cyclophosphamide OR Dexamethasone 8 mg PO
days 2-3
LOW EMETIC RISK (10-30%)
Bortezomib Dexamethasone 8 mg PO
Capecitabine (oral)
Cetuximab
Cytarabine < 1,000 mg/m2
Docetaxel
Etoposide (IV)
Fludarabine (oral)
Fluorouracil
Gemcitabine
Liposomal doxorubicin
Methotrexate (IV)
Mitomycin
Mitoxantrone
Paclitaxel
Pemetrexed
Teniposide
Topotecan
Trastuzumab
MINIMAL EMETIC RISK (<10%)
Bevacizumab No antiemetic is routinely
Bleomycin administered
Busulfan
Chlorambucil (oral)
2-Chlorodeoxyadenosine
Erlotinib (oral)
Fludarabine (IV)
Gefitinib (oral)
Hydroxyurea (oral)
Methotrexate (oral)
L-phenyalanine mustard (oral)
Rituximab
6-Thioguanine (oral)
Vinblastine
Vincristine
Vinorelbine
COMBINATION CHEMOTHERAPY Administer antiemetics appropriate for the component
chemotherapeutic agent of greatest emetic risk
MULTIPLE CONSECUTIVE DAYS OF Administer antiemetics appropriate for the risk class of the
CHEMOTHERAPY chemotherapy for each day of the chemotherapy (Aprepitant and

palonosetron have not been investigated in this setting)
SPECIAL EMETIC PROBLEMS
ANTICIPATORY EMESIS PREVENTION: use most active antiemetic regimens appropriate for
the chemotherapy being administered to prevent acute or delayed
emesis; Lorazepam or similar drugs
TREATMENT: behavioral therapy with systematic desensitization
HIGH DOSE CHEMOTHERAPY 5-HT3 serotonin receptor antagonist + corticosteroid + dopamine
antagonist in full doses; explore the addition of aprepitant
VOMITING & NAUSEA DESPITE 1. Careful evaluation of risk, antiemetic, chemotherapy, tumor, and
RECOMMENDED PROPHYLAXIS concurrent disease, and medication factors
2. Ascertain that the best regimen is being administered for the
emetic setting
3. Consider adding an lorazepam or alprazolam to the regimen
4. Consider substituting a high-dose intravenous metoclopramide for
the 5-HT3 antagonist or adding a dopamine antagonist to the
regimen
OTHER ANTI-EMETIC DRUGS
DOPAMINE ANTAGONISTS (TID-QID)

Metoclopramide 20-30 mg/day
Prochlorperazine 1020 mg/day
Domperidone 20 mg/day PO
Metopimazine 1530 mg/day IV as continuous infusion
CORTICOSTEROIDS (once daily)
Prednisolone 100-150 mg/day
Methylprednisolone 100 mg/day IV
OTHERS (OD-QID)
Lorazepam 1-2 mg/day
B. RADIATION-INDUCED EMESIS
HIGH EMETIC RISK (>90%)

Total body Prophylaxis with 5-HT3 serotonin receptor antagonist +
Dexamethasone before each fraction and at least 24o
after
MODERATE EMETIC RISK (60-90%)
Upper abdomen hemibody RT Prophylaxis with 5-HT3 serotonin receptor antagonist
Upper abdomen, Abdomino-pelvic, Mantle, Craniospinal before each fraction
RT
Cranial radiosurgery
LOW EMETIC RISK (30-60%)
Lower thorax & pelvis Prophylaxis or rescue with 5-HT3 serotonin receptor
Cranium (radiosurgery) antagonist before each fraction
Craniospinal
MINIMAL EMETIC RISK (<30%)
Head & neck Rescue with dopamine receptor antagonist or 5-HT3

Cranium serotonin receptor antagonist and continued
Extremities prophylactically for each remaining fraction
Breast
REFERENCES:
1. Kris MG, Hesketh PJ, Somerfield MR, et al: American Society of Clinical Oncology Guideline for Antiemetics in
Oncology: Update 2006. Journal of Clinical Oncology 24 (18): 2932-2947, 2006.
2. European Society for Medical Oncology Guidelines Working Group: Chemotherapy-Induced Nausea and
Vomiting: ESMO Clinical Recommendations for Prophylaxis. Annals of Oncology 18 (s2): ii83-ii85, 2007.

II. GUIDELINES FOR THE USE OF WHITE BLOOD CELL GROWTH FACTORS
DEFINITION
Febrile neutropenia (FN) a rise in axillary temperature to > 38.5oC for a duration of > 1o
while having an absolute neutrophil count (ANC) < 0.5 x 109/L
INDICATIONS
1. Primary prophylactic CSF

a. if the risk of FN is ~ > 20%
DISEASE SITE CHEMOTHERAPY
Cervix Paclitaxel Cisplatin
Ovary Docetaxel
Paclitaxel
Topotecan
Sarcoma Doxorubicin
Ifosfamide
MAID
b. patients at high risk of developing FN
x Age > 65 years old
x Poor performance status
x Previous episodes of FN
x Extensive prior treatment including large RT ports
x Administration of combined chemotherapy
x Cytopenias due to bone marrow involvement of tumor
x Poor nutritional status
x Presence of open wounds or active infections
x More advanced cancer
x Other serious co-morbidities / immunodeficiency
2. Secondary prophylactic CSF for patients who experienced a neutropenic complication from a prior cycle of
chemotherapy (for which primary prophylaxis was not received), in which a reduced dose may compromise
DFS or OS or treatment outcome
3. Therapeutic use of CSFs in patients with FN who:

a. Are at high-risk for infection-associated complications
b. Have prognostic factors that are predictive of poor clinical outcomes
High-Risk Features:
x Prolonged (> 10 days) neutropenia
x Profound neutropenia (< 0.1 x 109/L)
x Age > 65 years
x Uncontrolled primary disease
x Pneumonia
x Sepsis syndrome (hypotension & multiorgan failure)
x Invasive fungal infection
x Being hospitalized at the time of development of fever
c. Are receiving RT alone, if prolonged delays secondary to neutropenia are expected

NOTES:
o CSFs should not be routinely used for patients with afebrile neutropenia
o CSFs should not be routinely used as adjunctive treatment with antibiotic therapy for patients with FN
o CSFs should be avoided in patients receiving concomitant chemotherapy and radiation therapy, particularly
involving the mediastinum due to an increase risk of complications and death
DOSE & ADMINISTRATION
G-CSF 5 g/kg/d & GM-CSF 250 g/m2/d SC, given 24o to 72o after chemotherapy, continued until reaching
ANC > 2-3 x 109/L
Pegfilgrastim 6 mg SC SD, given 24o after chemotherapy
SIDE EFFECTS: bone, joint pain, arthralgias
REFERENCES:
1. Smith TJ, Klatcheressian J. Lyman GH, et al: 2006 Update of Recommendations for the Use of White Blood
Cell Growth Factors: An Evidence-Based Clinical Practice Guideline. Journal of Clinical Oncology 24 (19):
3187-3205, 2006.
2. European Society for Medical Oncology Guidelines Working Group: Hematopoietic Growth Factors: ESMO
Recommendations for the Application. Annals of Oncology 18 (s2): ii89-ii91, 2007.
3. National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology Version 1.2007.
4. EORTC Guidelines for the use of G-CSF, 2006.

III. GUIDELINES FOR THE USE OF EPOETIN AND DARBEPOETIN
DEFINITION
o a decrease in hemoglobin (Hb) level below normal lower limit, either disease or therapy related
o MILD anemia Hb > 10 g/dl and < 11.9 g/dl
MODERATE anemia Hb > 8.0 and < 9.9 g/dl
SEVERE anemia Hb < 8.0 g/dl
GENERAL RECOMMENDATION
o consider other correctable causes of anemia before initiating therapy with stimulants of erythropoiesis:
o thorough drug exposure history
o review of peripheral blood smear
o consider Fe, folate & B12 deficiency
o assess for occult blood loss
o assess for renal insufficiency
o Coombs testing for patients with CLL, NHL & with history of autoimmune disease
ASCO ESMO
INDICATIONS
1. Chemotherapy-induced anemia Hb < 12 g/dL regardless of the cause of anaemia, if

2. Anemia associated with low-risk myelodysplasia necessary in combination with RBC transfusion
3. Anemia in patients with non-myeloid hematological
malignancies who demonstrated no improvement in
hematologic outcomes following chemotherapy
CONTRAINDICATION
Anemia associated with malignancy among patients with

either solid or non-myeloid hematological malignancies
who are not receiving concurrent chemotherapy
INITIATION OF THERAPY
o Hb approaching, or has fallen below, 10 g/dL Hb < 12 g/dL

o Hb < 12 g/dL, but never fallen near 10 g/dL, depending
on clinical circumstances, including elderly with limited
cardiopulmonary reserve, underlying CAD or
symptomatic angina, substantially reduced exercise
capacity, energy, or ability to carry out ADLs
RBC transfusion also an option If necessary in combination with RBC transfusion

EPOETIN DARBEPOETIN
Initial dose 150 U/kg SC TIW 40,000 U SC weekly 2.25 mcg/kg SC weekly or
500 mcg SC every 3
weeks

Dose increase Increase to 300 U/kg TIW if Increase to 60,000 U SC Increase to 4.5 mcg/kg
no reduction in transfusion weekly if no increase in Hb every week (or every 3
requirements or rise of 1-2 by > 1 g/dL after 4 wks of weeks) if there is < 1 g/dL
g/dL in Hb after 8 wks therapy, in the absence of increase in Hb after 6 wks
OR 450 U/kg SC every RBC transfusion
week
Dose reductions Decrease by 25% when Hb approaches 12 g/dL or Hb Decrease by 40% when
increases > 1 g/dL in 2 wks Hb > 11 g/dL or Hb
increases > 1 g/dL in 2
wks
Dose withholding If Hb > 12 g/dL, withhold dose until Hb < 11 g/dL If Hb > 12 g/dL, withhold
Restart dose at 25% below previous dose dose until Hb=11 g/dL.
Restart dose at 40% below
previous dose
ADVERSE EFFECT:
o Thromboembolism
weigh the risk of thromboembolism in patients for whom epoetin or darbepoetin are prescribed
specific risk factors have not been defined; established general risk factors:
o Previous history of thromboses
o Surgery
o Prolonged periods of immobilization or limited activity
o Multiple myeloma patients on thalidomide or lenalidomide & doxorubicin or corticosteroids
* No data on concomitant use of anticoagulants or aspirin to modulate this risk
*** NOTE: Cancer patients who received erythropoiesis-stimulating agents (ESAs) were found to have
increased VTE risks (7.5% vs 4.9%; Relative risk, 1.57; 95% CI, 1.31-1.87) and increased
mortality risks (Hazard ratio, 1.10; 95% CI, 1.01-1.20) in a review article published in February
2008. The authors raise concern about the safety of ESA administration to patients with
cancer.3
REFERENCES:
1. Rizzo JD, Somerfield MR, Hagerty KL, et al: American Society of Clinical Oncology / American Society of
Hematology 2007 Clinical Practice Guideline Update on the Use of Epoetin and Darbepoetin. Journal of Clinical
Oncology 25 (34): 1-17, 2007.
2. Greil R and Thodtmann R: Erythropoietins in Cancer Patients: ESMO Recommendations for Use. Annals of
Oncology 18 (s2): ii86-ii88, 2007.
3. Bennett CL, Silver SM, Djulbegovic B, et al. Venous thromboembolism and mortality associated with
recombinant erythropoietin and darbepoetin administration for the treatment of cancer-associated anemia.
JAMA 2008; 299 (8): 914-924.

IV. GUIDELINES FOR THE USE OF CHEMOTHERAPY AND RADIOTHERAPY PROTECTANTS
A. MESNA
A. MESNA WITH IFOSFAMIDE

- recommended to decrease incidence of Ifosfamide-associated urothelial toxicity

Ifosfamide dose < 2 g/m2/d, Daily dose of Mesna equals 60% of total daily dose of Ifosfamide, given 15
short infusion mins before and 4o & 8o after administration of each dose of Ifosfamide
Continuous-infusion Mesna dose equals 20% of total Ifosfamide dose administered as bolus,
Ifosfamide followed by continuous infusion equal to 40% of Ifosfamide dose, continuing
for 12o to 24o after completion of the Ifosfamide infusion
Ifosfamide dose > 2.5 Insufficient evidence on which to base a recommendation. More frequent
g/m2/d and prolonged Mesna dosage may be necessary
Oral Mesna Mesna equals to 20% of Ifosfamide dosage given IV bolus at the time of
Ifosfamide administration, then Mesna tabs given orally in a dosage equal to
40% of the Ifosfamide dose at 2o and 6o after each dose of Ifosfamide
B. MESNA WITH CYCLOPHOSPHAMIDE

- Mesna + saline diuresis or forced saline diuresis recommended to decrease the incidence of urothelial
toxicity associated with high-dose Cyclophosphamide in the setting of stem-cell transplantation
B. AMIFOSTINE
A. IN CHEMOTHERAPY-ASSOCIATED COMPLICATIONS
o NEPHROTOXICITY
- may be considered for prevention of nephrotoxicity in patients receiving Cisplatin-based chemotherapy
for advanced ovarian cancer or non-small cell lung cancer
- should not be administered to patients in settings where chemotherapy can produce a significant
survival advantage or cure, except in the context of a clinical trial
o NEUTROPENIA
- may be considered for the reduction of neutropenia-associated events in patients receiving alkylating-
agent chemotherapy
- consider chemotherapy dose reduction as alternative
o THROMBOCYTOPENIA, NEUROTOXOCITY & OTOTOXICITY, PACLITAXEL-ASSOCIATED
NEUROTOXICITY
- Insufficient data
B. IN RADIOTHERAPY-ASSOCIATED COMPLICATIONS
o XEROSTOMIA
- may be considered to decrease incidence of acute & late xerostomia in patients undergoing
fractionated RT in the head & neck region
o MUCOSITIS
- insufficient data

WITH CHEMOTHERAPY WITH RADIOTHERAPY
910 mg/m2 IV, over 15 mins, 30 mins before 200 mg/m2/d, slow IV push over 3 mins, 15-30 mins
chemotherapy before each fraction of RT
o Antiemetics before Amifostine administration

o Pretreatment with IVF should be considered
o BP taken just before and q3-5 mins during the infusion. Discontinue if BP declines significantly or patient
becomes symptomatic. If hypotension develops, discontinue Amifostine, administer saline & place patient in
Trendelenburg position
REFERENCE:
1. Schuchter LM, Hensley ML, Meropol NJ, Winer EP: 2002 Update of Recommedations for the Use of
Chemotherapy and Radiotherapy Protectants: Clinical Practice Guidelines of the American Society of
Clinical Oncology. Journal of Clinical Oncology 20 (12): 2895-2903, 2002.

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

Aetiology/Harm diagnosis/symptom decision analyses
prevalence study
1a SR (with homogeneity*) SR (with SR (with homogeneity*) of SR (with homogeneity*) of SR (with homogeneity*)
of RCTs homogeneity*) of Level 1 diagnostic studies; prospective cohort studies of Level 1 economic
inception cohort CDR with 1b studies from studies
studies; CDR different clinical centres
validated in different
populations
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-series Absolute SpPins and All or none case-series Absolute better-value
SnNouts or 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 either Level >2 diagnostic 2b and better studies of Level >2 economic
retrospective cohort studies studies
studies or untreated
control groups in RCTs
2b Individual cohort study Retrospective cohort Exploratory** cohort study Retrospective cohort study, Analysis based on
(including low quality study or follow-up of with goodreference 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 Analysis based on
Study without consistently cohort 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 superseded Analysis with no
quality cohort and case- quality prognostic or non-independent reference standards sensitivity analysis
control studies ) cohort studies***) reference standard
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
or based on physiology, appraisal, or based on based on physiology, based on physiology, bench appraisal, or based on
bench research or "first physiology, bench bench research or "first research or "first principles" economic theory or
principles" research or "first principles" "first 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)
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.
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.

APPENDIX B
GEOGRAPHICAL DISTRIBUTION OF GYNECOLOGIC ONCOLOGISTS IN THE PHILIPPINES
NATIONAL CAPITAL REGION REGION II

Rainerio S. Abad, M.D. Melchor C. dela Cruz, Jr., M.D. Isabela/Nueva Vizcaya
Amuerfina D. Albano, M.D. REGION III
Leo Francis N. Aquilizan, M.D. Ronald Agustine O. Campos, M.D. Pampanga
Edna C. Banta, M.D. Agnes M. Gaddi, M.D. Pampanga
Aida J. Bautista, M.D. Esther R. V. Ganzon, Jr., M.D. Cabanatuan City, Nueva Ecija
Doris R. Benavides, M.D. Corazon R. Valdez, M.D. Olongapo City, Zambales
Glenn B. Benitez, M.D. Jocelyn Z. Mariano, M.D. Meycauayan, Bulacan
Isidro B. Benitez, M.D. Grace D. Sabado, M.D. Tarlac, Tarlac
Manuel N. Borja, M.D. Elmer R. Santos, M.D. Balanga, Bataan
Judith G. Cabanela, M.D. REGION IV
Teresita B. Cardenas, M.D. Coleta B. Arias, M.D. Lucena City, Quezon
Melinda M. Cayabyab, M.D. Marie Aleli R. De Castro Lipa City, Batangas
Percida S. Cocos, M.D. Belen T. Garana, M.D. Lucena City Quezon
Lilli May T. Cole, M.D. Arlene B. Huevos, M.D. San Pablo City, Laguna
Benjamin D. Cuenca, M.D. Gina P. Motil, M.D. Lucena City, Quezon
Elsie, R. Dancel, M.D. Menandro A. Villadelgado, M.D. Tanauan, Batangas
Rey H. delos Reyes, M.D., M.H.S.A. Andrew Rouldan B. Buizon, M.D. Dasmarinas, Cavite
Efren J. Domingo, M.D., Ph.D. Aina R. Sales-Diaz, M.D. - Bian, Laguna
Rommel Z. Dueas, M.D. Salvador Luis R. Villanueva, M.D. Los Baos, Laguna
Aris Luke I. Dungo, M.D. REGION V
Emilio Glenn B. Evangelista, M.D. Alma M. Bresnan, M.D. Naga City, Camarines Sur
Jay Arnold F. Famador, M.D. Rona F. Raola, M.D. Legaspi, Albay
Victoria S. Fernando, M.D. REGION VI
Ma. Julieta Corazon V. Germar, M.D. Norma L. Diy Bacolod City
Gil S. Gonzalez, M.D. Ma. Lora C. Tupas, M.D. Iloilo City
Cecilia L. Llave, M.D., Ph.D. Arnold P. Liwag, M.D. Iloilo City/Bacolod City
Genara M. Limson, M.D. REGION VII
Jericho Thaddeus P. Luna, M.D. Patricia Ann S. Coronel, M.D. Cebu
Manuel S. Manabat, M.D. Pherdes E. Galbo, M.D. Cebu
Augusto M. Manalo, M.D. Evangeline M. Mercader, M.D. Cebu
Jose B. Moran, M.D. Raymond S. Sulay, M.D. Cebu
Virgilio R. Oblepias, M.D. REGION VIII
Scheryl B. Pua, M.D.
Mary Christine F. Palma, M.D. REGION IX
Wilhelmina D. Rivera, M.D. Ma. Gay M. Gonzales, M.D. Zamboanga City
Filomena S. San Juan, M.D. REGION X
Ma. Lilibeth L. Sia Su, M.D. Fe Marissa G. Mercado, M.D. Cagayan de Oro
Rene V. Sotto, M.D. Raymond S. Sulay, M.D. Iligan City
Luciano S.J. Sotto, M.D. REGION XI
Elizabeth E. Espino-Strebel, M.D. Carol Marjorie P. Flavier, M.D. Davao City
Ma. Patricia L. Sun, M.D. Concepcion D. Rayel Davao City
Ma. Cynthia F. Tan, M.D. Helen Grace T. Santos, M.D. Davao City
German C. Tan-Cardoso, M.D. Constancia Wilhelmina T. Solis, M.D. Davao City
Rafael S. Tomacruz, M.D. REGION XII
Jean Ann B. Toral, M.D. Helen D. Yambao, M.D. North Cotabato
John-David V. Zamora, M.D. Myra Joy G. Maduramente-Mann, M.D. General Santos
REGION I
Teresita P. Agbanlog, M.D. Baguio City
Richard Ronald B. Cacho, M.D. Pangasinan/La Union
Ruth Judith V. Cristobal, M.D. Ilocos Sur
Yvonne T. Soriano, M.D. Baguio City/La Union

APPENDIX C
STAGING OF GYNECOLOGIC CANCERS
I. FIGO STAGING OF CERVICAL CANCER
STAGE 0 Carcinoma in situ; Cervical intraepithelial neoplasia grade III

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. All macroscopically
visible lesions even with superficial invasion are allotted Stage IB carcinomas.
Invasion is limited to a measured stromal invasion with a maximal depth of 5.0 mm
and a horizontal extension of not more than 7.0 mm. Depth of invasion should not be
more than 5.0 mm related to the base of the epithelium of the original tissue
superficial or glandular. The involvement of the vascular spaces venous or
lymphatic should not change the stage allotment.
Stage IA1 Measured stromal invasion of not more than 3.0 mm in depth and extension of not
more than 7.0 mm
Stage IA2 Measured stromal invasion of more than 3.0 mm and not more than 5.0 mm with an
extension of not more than 7.0 mm
Stage IB Clinically visible lesions limited to the cervix uteri, or subclinical cancers greater than
Stage IA
Stage IB1 Clinically visible lesions not larger than 4.0 cm
Stage IB2 Clinically visible lesions larger than 4.0 cm
STAGE II The carcinoma extends beyond the cervix but has not extended to the pelvic wall.
The carcinoma involves the vagina but not as far as the lower third.
Stage IIA No obvious parametrial involvement
Stage IIB Obvious parametrial involvement
STAGE III The carcinoma has extended to the pelvic wall. On rectal examination, there is no
cancer-free space between the tumor and the pelvic wall. The tumor involves the
lower third of the vagina. All cases with hydronephrosis or nonfunctioning kidney are
included, unless they are known to be due to other causes.
Stage IIIA 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 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
II. ENDOMETRIAL CANCER
A. 1988 FIGO SURGICAL STAGING FOR ENDOMETRIAL CANCER

STAGE IA G123 Tumor confined to endometrium
IB G123 Invasion to less than one-half of the myometrium
IC G123 Invasion to more than one-half of the myometrium
STAGE IIA G123 Endocervical glandular involvement only
IIB G123 Cervical stromal invasion
STAGE IIIA G123 Tumor invades serosa and/or adnexa and/or (+) peritoneal cytology
IIIB G123 Vaginal metastases
IIIC G123 Metastases to pelvic and/or para-aortic lymph nodes
STAGE IVA G123 Tumor invasion of bladder and/or bowel mucosa
IVB G123 Distant metastases including intra-abdominal and/or inguinal nodes

B. 1971 FIGO CLINICAL STAGING FOR ENDOMETRIAL CANCER
STAGE 0 Carcinoma in situ.
STAGE I The carcinoma is confined to the corpus.
Stage IA The length of the uterine cavity is 8 cm or less.
Stage IB The length of the uterine cavity is more than 8 cm.
STAGE II The carcinoma has involved the corpus and the cervix but has not extended outside the
uterus.
STAGE III The carcinoma has extended outside the uterus but not outside the true pelvis.
STAGE IV The carcinoma has extended outside the true pelvis or has obviously involved the
mucosa of the bladder or rectum. A bullous edema as such does not permit a case to
be allocated to Stage IV.
Stage IVA Spread of the growth to adjacent organs.
Stage IVB Spread to distant organs.
III. FIGO STAGING OF 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.

IV. FIGO STAGING OF 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.
V. VULVAR CANCER
A. 1995 FIGO STAGING FOR VULVAR CANCER

STAGE 0 Carcinoma in situ; Intraepithelial carcinoma
STAGE I Tumor confined to the vulva or perineum; 2 cm or less in greatest dimension; no
nodal metastases
Stage IA Stromal invasion < 1 mm
Stage IB Stromal invasion > 1 mm
STAGE II Tumor confined to the vulva or perineum; more than 2 cm in greatest dimension; no
nodal metastases
STAGE III Tumor of any size with adjacent spread to the lower urethra, vagina, or anus; and/or
unilateral regional lymph node metastases
STAGE IV Tumor extends beyond the true pelvis or involving the bladder or rectal mucosa
Stage IVA Tumor invades the upper urethra, bladder mucosa, rectal mucosa, pelvic bone, or
bilateral regional lymph node metastases
Stage IVB Any distant metastases, including pelvic lymph nodes
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

VI. FIGO STAGING OF VAGINAL CANCER
STAGE 0 Carcinoma in situ; Intra-epithelial carcinoma

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 Spread of the growth to the adjacent organs 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. K 20 (Type I, MW 46 kDa ) and K 7 ( Type II, MW 54 kDa )
o Endometrioid and serouis carcinoma of the ovary are K7 positive and K 20 negative
o Majority of mucinous carcinoma of the ovary, especially those of colonic type, are K7 positve or K
20 positive
o In mixed germ cell tumor, K7 is selectively expressed by trophoblastic components
2. K 8 ( Type II, MW 52 kDa ) , K 18 ( Type I, MW 45 kDa ), K 19 ( Type I, MW 40 kDa )

o Most adenocarcinoma of gynecologic origin and germ cell tumor ( except Dysgerminoma ) are
positive with K 8 and K 18
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 K 8.
3. K 4 ( Type II, MW 58 kDa ), K 13 ( 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 K 13.
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 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
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 ) Non specificity 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, Langerhans 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 ( CA 125 ) ( OC 125 ) and CA 19 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 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 feto protein ( 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, Ki 67 ranged from 1 to 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 fro colonic adenocarcinoma. Gastric carcinoma is frequently K 7+, K 20+ or
K 7-, K 20+. Pancreasatic carcinoma is usually K 7+, K 20+.
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: -fetoprotein- (or +/-), LeuM-1 (CD15)+.

Yolk sac tumor: -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+, -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 Response Complete resolution of all evidence of disease Complete resolution of all evidence of disease
(CR) lasting at least 1 month
Partial Response A decrease of 50% in the product of the A decrease of 30% in the baseline sum
(PR) diameters (maximal and minimal) of all longest diameters of all measurable disease*
measurable lesions lasting at least 1 month without the development of new lesions
without the development of new lesions
Stable Disease (SD) A decrease of < 50% or an increase of < 25% A decrease of < 30% or an increase of < 20% in
in the product of the diameters of all the baseline sum longest diameters of all
measurable disease measurable disease*
Progression An increase of 25% in the measurable An increase of 20% in the baseline sum
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

0 0 90-100 Fully active; Unrestricted activities of
daily living.
1 1 70-80 Ambulatory but restricted in strenuous
activity.
2 2 50-60 Ambulatory but capable of self-care;
Unable to work; Out of bed greater than
50% of waking hours.
3 3 30-40 Limited self-care; Confined to bed or
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 : ECOG Score 0 2
Chemotherapy : ECOG Score 0 2
Radiotherapy : 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
Womens 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 Womens 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
Medscape Oncology http://www.medscape.com/home/topics/oncology/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 and http://www.figo.org
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 Prevention http://cdc.gov
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


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Society of Gynecologic Oncologists of the Philippines

SGOP TREATMENT GUIDELINES 2008 1

The proper management of any malignancy requires an appreciation of its many

REY H. DE LOS REYES, M.D., FSGOP

SGOP TREATMENT GUIDELINES 2008 2

It is recommended that the specific diagnostic or therapeutic procedures mentioned

Efren J. Domingo, M.D.,Ph.D.

SGOP TREATMENT GUIDELINES 2008 3

REY H. DELOS REYES, MD, MHSA

MA. CYNTHIA F. TAN, MD

MA. LILIBETH L. SIA SU, MD

MARY CHRISTINE F. PALMA, MD

EFREN J. DOMINGO, MD, PhD

PHILIPPINE BOARD OF GYNECOLOGIC ONCOLOGY

Gil S. Gonzalez, M.D.

THE SOCIETY OF GYNECOLOGIC ONCOLOGISTS OF THE PHILIPPINES

SGOP TREATMENT GUIDELINES 2008 4

2008 GENERAL MEMBERSHIP

SGOP TREATMENT GUIDELINES 2008 5

ENDOMETRIAL CANCER & UTERINE SARCOMAS

OVARIAN & FALLOPIAN TUBE CANCERS

VULVAR & VAGINAL CANCERS

PREVENTION & TREATMENT OF COMPLICATIONS

SGOP TREATMENT GUIDELINES 2008 6

1. Cervical cancer is diagnosed by biopsy1(Benedet 2006).

I. Biopsy Proven Premalignant Lesions11(ASCCP 2006 Guidelines)

SGOP TREATMENT GUIDELINES 2008 7

2. Not desirous of pregnancy

SGOP TREATMENT GUIDELINES 2008 8

c. Radical vaginal trachelectomy and laparoscopic lymphadenectomy23 inclusion criteria:

SGOP TREATMENT GUIDELINES 2008 9

FINAL HISTOPATHOLOGY REPORT OF CERVICAL CANCER SPECIMENS:

SGOP TREATMENT GUIDELINES 2008 10

SURGICO-PATHOLOGIC PROGNOSTIC FACTORS

PROGNOSTIC FACTORS ADJUVANT TREATMENT

3. Positive lines of resection Parametrium Concurrent chemotherapy and

Note: If para-aortic sampling not

6. Endomyometrial invasion Concurrent chemotherapy and pelvic EBRT52[Level C]

A. INCIDENTAL FINDING OF INVASIVE CANCER AFTER SIMPLE HYSTERECTOMY

SGOP TREATMENT GUIDELINES 2008 11

Stage 1A1, no LVSI Observation 1 [ Level 2A]

Complete parametrectomy with upper

B. In Association with Pregnancy

SGOP TREATMENT GUIDELINES 2008 12

PERSISTENT OR RECURRENT DISEASE

SGOP TREATMENT GUIDELINES 2008 13

COMBINATION CHEMOTHERAPY 1,44,68,69

HORMONAL REPLACEMENT THERAPY (HRT) AFTER TREATMENT OF CERVICAL CANCER,

SGOP TREATMENT GUIDELINES 2008 14

SGOP TREATMENT GUIDELINES 2008 15

SGOP TREATMENT GUIDELINES 2008 16

SGOP TREATMENT GUIDELINES 2008 17

SGOP TREATMENT GUIDELINES 2008 18

For premenopausal women:

x IF NORMAL, continue MPA at 5 mg x 10 days/month for 12

x IF PERSISTENT, increase dose to 40-100 mg daily x 3

x IF NORMAL, decrease MPA to 10 mg OD x 14 days for 12

For postmenopausal women:

Other treatment options:

SGOP TREATMENT GUIDELINES 2008 19

SGOP TREATMENT GUIDELINES 2008 20

Indications for aortic node sampling:10

STAGE I: Confined to the Corpus