CONTENTS

CERVICAL CANCER

I. Introduction 4
II. Histopathologic Classification 4
III. FIGO Stage ( 2008 ) 5
IV. Diagnostic Procedures 6
V. Therapy
Management of Early Stage (Ia1 & Ia2 ) 9
Management of Early Stage (Ib1/IIa1 or Ib2/IIa2 (>4-6 cm) 10
Management of Ib2, IIa2 (>6 cm) and IIb 11
Management of Locally Advanced Stage ( III and IVa ) 12
Management of Cervical Cancer in Pregnancy
Stage Ia1 & Ia2 ( LVSI negative ) 13
Stage Ib2, IIa2 – IVa 14
Stage IVb 15
Management of Stage IVb 16
Management of Cervical Cancer After Simple Hysterectomy 17
Management of Cervical Cancer ( IIb-IVb ) with Ovarian Mass 18
VI. Follow up 19
VII. Recurrence 19

OVARIAN CANCER ( EPITHELIAL )

I. Introduction 20
II. Histopathologic Classification 20
III. FIGO Stage ( 2008 ) 21
IV. FIGO Stage ( January 2014 ) 22
V. Diagnostic Procedures 24
VI. Therapy
Management of Adnexal Mass ( appendix ) 25
Management of Operated Patients (Referred / Not Fully Staged) 27
Management of Early Stage (I-IIa presumed preoperatively ) 27
Management After Surgery 28
Management of Advanced Stage 29
VII. Follow up 30
VIII. Recurrence 30

OVARIAN CANCER ( NON EPITHELIAL ) - GERM-CELL TUMOR

I. Introduction 32
II. Histopathologic Classification 32
III. Diagnostic Procedures 32
IV. Therapy
Surgical Management 34
V. Follow up 35
VI. Recurrence 35

  1  
SEX-CORD STROMAL TUMOR

I. Introduction 36
II. Histopathologic Classification 36
III. Diagnostic Procedures 36
IV. Therapy
Surgical Management 37
V. Follow up 37
VI. Recurrence 37

MANAGEMENT OF BORDERLINE MALIGNANCY

OF OVARIAN TUMOR 38

ENDOMETRIAL CANCER

I. Introduction 39
II. Histopathologic Classification 39
III. FIGO Stage ( 2009 ) 40
IV. Diagnostic Procedures 40
V. Therapy
Management of Stage I ( Endometrioid ) 41
Management of Stage II ( Endometrioid ) 42
Management of Stage III 42
Management of Stage IV 43
Management of Endometrial Cancer Diagnosed After Surgery 43
Management of Serous Papillary or Clear Cell Endometrial Ca 44
VI. Follow up 44
VII. Recurrence 45

VULVAR CANCER

I. Introduction 46
II. Histopathologic Classification 46
III. FIGO Stage ( 2008 ) 46
IV. Diagnostic Procedures 48
V. Therapy
Management of Vulva Cancer 49
Management of T3-T4 Vulva Cancer 50
Management of M2-M3 of Vulvar Cancer 51
Adjuvant Treatment 51
Management of Clinically Suspicious Groin Nodes 52
Management of Clinically Obvious Groin Nodes 53
Management of Advanced Primary Tumor 54

GESTATIONAL TROPHOBLASTIC NEOPLASIA

I. Introduction 55
II. Histopathologic Classification 55

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III. FIGO Stage ( 2000 ) 55
IV. Diagnostic Procedures 56
V. Therapy
Gestational Trophoblastic Disease 57
Management of Low Risk GTD 58
Management of High Risk GTN 59
Management of Placental Site Trophoblastic Tumor 60
VI. Follow up 60

UTERINE SARCOMA

I. Introduction 61
II. Histopathologic Classification 61
III. FIGO Stage ( 2000 ) 61
IV. Diagnostic Procedures 62
V. Therapy
Uterine Sarcoma 63
Management of Carcinosarcoma 63
Management of Low Grade Endometrial Stromal Sarcoma 64
Management of Leiomyosarcoma 65
Management of Undifferentiated Sarcoma ( = High Grade ESS ) 65
Management of Operated Patients ( without BSO ) 66
VI. Follow up 66
VII. Recurrence 66

VAGINAL CANCER

I. Introduction 67
II. Histopathologic Classification 67
III. FIGO Stage ( 2006 ) 68
IV. Diagnostic Procedures 68
V. Therapy
Management of Early Stage 69
Management of Advanced Stage ( II-IVa ) 70
Management of Advanced Stage ( IVb ) 70
VI. Follow up 71
VII. Recurrence 71

APPENDIX
Chemotherapy Regimens 72
Cisplatin Hydration 73
Determination of Clearance Creatinine 75
Suggested Cisplatin dose modifications based on clearance creatinine 75
Suggested Carboplatin dose modifications based on clearance creatinine 76
Determination of Target Area Under the Curve (AUC) 76
Guidelines for Percentage of Chemotherapy 76
Guidelines for Chemotherapy Dosage Based on Hepatic Function 77
Guidelines for Chemotherapy Dosage Based on Renal Function 78

  3  
 CERVICAL CANCER

I. Introduction

-­‐ Cervical cancer is one of the leading causes of cancer death in women in the
developing world
-­‐ An estimated 95% of women in developing countries have never been screened
for cervical cancer
-­‐ Over 80% of women newly diagnosed with cervical cancer live in developing
countries; most are diagnosed when they have advanced disease.
-­‐ Worldwide incidence rates of cervical cancer per 100,000 females ( all ages ),
age-standardised to the WHO standard population ( 2005 ). In Indonesia the
incidence rate is 15-29.9 per 100,000 females.
-­‐ The cure rate for invasive cervical cancer is closely related to the stage of
disease at diagnosis and the availability of treatment.
-­‐ If left untreated, cervical cancer is almost always fatal.

II. Histopathological Classification

WHO classification of cervical epithelial tumors and SNOMED morphology coding

• Squamous tumors and precursors
-­‐ Squamous carcinoma, not otherwise specified 80703
-­‐ Keratinizing 80713
-­‐ Non-keratinizing 80723
-­‐ Basaloid 80833
-­‐ Verrucous 80513
-­‐ Warty 80513
-­‐ Papillary 80523
-­‐ Lymphoepithelioma-like 80823
-­‐ Squamotransitional 81203
-­‐ Early invasive (microinvasive) squamous cell carcinoma 80763
-­‐ Squamous intraepithelial neoplasia
-­‐ Cervical intraepithelial neoplasia (CIN) 3 80772*
-­‐ Squamous cell carcinoma in situ 80702

• Glandular tumors and precursors

-­‐ Adenocarcinoma 81403
-­‐ Mucinous adenocarcinoma 84803
-­‐ Endocervical type 84823
-­‐ Intestinal 81443
-­‐ Signet-ring cell 84903
-­‐ Minimal deviation 84803
-­‐ Villoglandular 82623

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 • Endometrioid adenocarcinoma 83803
-­‐ Clear cell adenocarcinoma 83103
-­‐ Serous adenocarcinoma 84413
-­‐ Mesonephric adenocarcinoma 91103
-­‐ Early invasive adenocarcinoma 81403
-­‐ Adenocarcinoma in situ 81402

• Other epithelial tumors

-­‐ Adenosquamous carcinoma 85603
-­‐ Glassycell carcinoma variant 80153
-­‐ Adenoid cystic carcinoma 82003
-­‐ Adenoid basal carcinoma 80983
-­‐ Neuroendocrine tumors
o Carcinoid tumor 82403
o Atypical carcinoid 82493
o Small cell carcinoma 80413
o Large cell neuroendocrine carcinoma 80133

• Undifferentiated carcinoma 80203

* In the United Kingdom, the preferred SNOMED code for CIN 3 is 74008.

III. FIGO Stage ( updated 2008 )

Stage I The carcinoma is strictly confined to the cervix (extension to the corpus
would be disregarded)
IA Invasive carcinoma which can be diagnosed only by microscopy, with deepest
invasion ≤5 mm and largest extension ≤7 mm
IA1 Measured stromal invasion of ≤3.0 mm in depth and extension of ≤7.0 mm
IA2 Measured stromal invasion of >3.0 mm and not >5.0 mm with an extension of
not >7.0 mm
IB Clinically visible lesions limited to the cervix uteri or pre-clinical cancers
greater than stage IA
IB1 Clinically visible lesion ≤4.0 cm in greatest dimension
IB2 Clinically visible lesion >4.0 cm in greatest dimension

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 Stage II Cervical carcinoma invades beyond the uterus, but not to the pelvic wall
or to the lower third of the vagina
IIA Without parametrial invasion
IIA1 Clinically visible lesion ≤4.0 cm in greatest dimension
IIA2 Clinically visible lesion >4 cm in greatest dimension
IIB With obvious parametrial invasion
Stage III The tumor extends to the pelvic wall and/or involves lower third of the
vagina and/or causes hydronephrosis or non-functioning kidney
IIIA Tumor involves lower third of the vagina, with no extension to the pelvic
wall
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 involved
(biopsy proven) the mucosa of the bladder or rectum. A bullous edema,
as such, does not permit a case to be allotted to Stage IV
IVA Spread of the growth to adjacent organs
IVB Spread to distant organs

IV. Diagnostic Procedures

A. Clinical

-­‐ Microinvasive cancers may be asymptomatic, and may be detected only on

investigation of an abnormal Pap smear.
-­‐ On the other hand, most cases of frankly invasive cervical cancer come to the
attention of providers and are diagnosed once they become symptomatic.
-­‐ If the woman is not sexually active, the disease may remain asymptomatic until it
is well advanced.

B. Physical examination
From head to toes :
• anemia
• supraclavicular node enlargement
• pleuraleffusion
• swelling of the lower limb

Pelvic examination
• External genital examination
• Speculum examination + tumor size measurement with clamp
• Bimanual examination (vaginal and rectovaginal examination)

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 Physical Examination

STAGE

SURE IN DOUBT / ADVANCED

EUA + cystoscopy

C. Histology

All biopsy specimen should be sent to Dr. Soetomo Hospital Pathology Department.
Abnormal pap smear → colposcopy ( see below )

D. Imaging

Ultrasound (pelvic & abdominal)

Hydronephrosis (+) à IVP/renogram(to see kidney function) /
Chest X-Ray
MRI ( for stage more than Ib )
CT scan

E. Laboratory

• Complete blood count

• RFT ( BUN, Serum creatinin → hitung Clearance creatinin )
• LFT ( SGOT, SGPT, Bilirubin direct dan total )
• Electrolyte (Na,K,Cl,Mg)
• Albumin
• SCC (if possible) à only for Squamous
• Urinalysis

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 COLPOSCOPY

Lesion (+) Lesion (-) Unsatisfied

Biopsy
ECC

Patients referred with cervical cancer :

Re-biopsy Visible lesion

Unvisible Lesion/Microinvasive

Get the previous slide (-)

(Within 1 week) COLPOSCOPY

  8  
 V. Therapy

MANAGEMENT OF EARLY STAGE

STAGE Ia1 & Ia2

Diagnosis is based on
CONIZATION

LVSI (-) LVSI (+)

Ia2

Radical hysterectomy + Node (+)

lymphadenectomy
Free Margin (+)
margin
EBRT
Observe Repeat conization or

or or Radical trachelectomy + Node (+)

er er lymphadenectomy

Simple Simple
Hysterectomy Hysterectomy Radical Hyst
or
EBRT

  9  
 MANAGEMENT OF EARLY STAGE

STAGE Ib1/IIa1 or
Ib2/IIa2 (>4-6 cm)

*Prognostic Factors:
Ovareksis should • Lymphnode status
Radical hysterectomy + • Radical margin
done in young
lymphadenectomy ± (vagina,
women ≤40 y.o
Salpingoophorectomy parametria)
• Parametrial
involvement
• LVSI
Histopathology parameters
(Prognostic Factors (PF)*)

PF (-) Squamous + 1 PF Squamous + 2 PF

Adenocarcinoma +1/2 PF
Adenosquamous + 1/2 PF

Follow up
Adjuvant EBRT Adjuvant chemo-radiation

While waiting :
**Cisplatin 75 mg/m2 every 3 weeks
max 6 courses

Note :
** If there is Cisplatin contraindication → consider to Carboplatin AUC 5 ( max. 6
courses ).

  10  
 MANAGEMENT OF EARLY STAGE

STAGE Ib2, IIa2 (>6 cm) Register for

and IIb radiation
 
Remove the bulky nodes
2
3-4x Cisplatin 50 mg/m weekly (>2 cm) in any stage
max 250 mg/m2 cumulative*

Respon (+) Respon (-) / Progress

Radical hysterectomy 3 x Pacli – Carbo 3 weekly

+ lymphadenectomy
± salpgingoovorectomy

Respon (+) Stable / Progress

PF (-) PF (+)
  Radiation
Standard
Follow up
adjuvant : EBRT

If more than 2 months

4 x Cisplatin 50mg/m2 weekly or

3 x Pacli Carbo 3 weekly ( depends
on previous chemotherapy that gave
response )

Note :
* If there is Cisplatin contradindication → replace with Paclitaxel – Carboplatin 3
courses 3 weekly.

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 MANAGEMENT OF LOCALLY ADVANCED STAGE

Register for
STAGE III &IVa
radiation

CT scan chest & whole abd to exclude

distant metastasis ( PET CT if
available )

Distant metastasis (+) Distant metastasis (-)

Chemoradiation
IVb
( concurrent )

3-4 x Cisplatin 50 mg/m2/

3 weekly**

Remove the bulky nodes

(>2 cm) in any stage
Max 250 mg/m2 cumulative

Radiation

Note :
*Need to be discussed
** If there is Cisplatin contraindication → stop any chemotherapy, just wait for radiation.

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 CERVICAL CANCER IN PREGNANCY

Stage Ia1 & Ia2 ( LVSI negative )

Pre-viable Viable

Desire to continue
pregnancy Caesarean Section

No Yes Conization 6 weeks after

CS
Future fertility wish Conization

No Yes Ia1 with Worse

free margin

Simple Pregnancy
hysterecto termination Continue
my + fetus + as normal
in situ conization Treat accordingly
pregnancy

  13  
 Cervical cancer stage IB2, IIA2 - IVA

Pre-viable Viable

Desire to continue
pregnancy

No Yes

Give chemo Pacli-

< 16 weeks ≥ 16 weeks Carbo when gest age
gest age gest age 16-28 weeks

Classical Caesarean
Section

See Cervical Cancer

Guideline

  14  
 Stage IVB

Pre-viable Viable

Desire to continue
pregnancy

No Yes

Give chemo palliative

< 16 weeks ≥ 16 weeks when gest age 16-28
gest age gest age weeks

Chemotherapy
paliative
Classical Caesarean
Termination of Section
pregnancy
Chemotherapy
paliative

Note :
Chemotherapy palliative : Pacli – Carbo

  15  
 MANAGEMENT OF CERVICAL CANCER IVB
( based on Abdomen + Thorax CT )

Abdomen + Thorax CT ( PET-CT if available )

Paraaortic lymph nodes only Other distant organ metastasis

FNAB
Small nodes Big nodes

Paliative

Node
debulking

Extended field radiotherapy

Note :
Paliative : Pacli-carbo chemotherapy.

  16  
 MANAGEMENT OF CERVICAL CANCER AFTER
SIMPLE HYSTERECTOMY

Gynecology Normal

Review Histopathology, tumor size,

surgical margin,stromal invasion, LVSI

Tumor size < 2 cm Tumor size ≥ 2 cm

Stromal invasion < 1 cm Stromal invasion ≥ 1 cm
LVSI (-) LVSI (+)
Surgical margin free Surgical margin (+)

(+) Chemoradiation
Bilateral Pelvic Lymph
Node Desection

(-) Follow up

Note :
All other conditions à chemoradiation.
After supravaginal hysterectomy à chemoradiation, except : small tumor and free
margin ( consider surgery ).

  17  
 MANAGEMENT OF CERVICAL CANCER ( IIb – IVb )
WITH OVARIAN MASS

Simple cyst

Treatment
according to the
CaCx stage
Complex cyst

Stage IIb Stage IIIa - IVb

Neoadjuvant chemo Surgery for mass removal

( Pacli – Carbo 3 cycles ) (VC)

Operable Non operable Benign Epithelial Cancer

Surgery Surgery for mass Treatment Staging

removal according to the
stage
( Cisplatin Pacli-Carbo 6x
Chemoradiation only )

Radiation
VI. Follow-Up

• Clinical examination
• Vaginal smear is not needed

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 • Every 3 months for 1 year, every 6 months for 2 years, every year until the
5th year
• Recurrence à PA/Imaging

VII. Recurrence

Recurrence

Local Recurrence Metastatic / Pelvic Side Wall

Recurrence

After surgery Palliative

After radiation
(non irradiated patients)

Chemo-radiation Pelvic exenteration Palliative

(Central recurrence and
exclude distant
metastasis)

Note :
1. If there is a suspicious recurrence, proof by biopsy.
2. Do evaluation under anesthesia together with urolog, radiotherapist and pelvic
surgeon. Determine operability.
3. If operable, distance metastasis with PET scan or CT scan ( abdomen and lungs )
must be excluded.
4. If pelvic exenteration will performed, comprehensive counseling about the
survival, DFS and complications during/after surgery ( including permanent
stoma ) is needed. Also counseling about the side effects of the procedure.
5. Pelvic exenteration is part of curative treatment ( 50% are cured ).

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 OVARIAN CANCER
I. Introduction
Malignant tumours of the ovaries occur at all ages. Major histologic types occur in
different age groups.
For women less than 20 years old of age, germ cell tumours constitute the majority of
cases while epithelial ovarian cancers (EOC) are primarily seen in women older than
50 years.
EOC is a relatively common disease in the USA. The lifetime risk of a woman in the
United States to develop ovarian cancer is approximately1 in 70. Approximately 23%
of gynaecologic cancers are ovarian in origin, but 47% of all deaths from cancer of the
female genital tract occur in women with ovarian cancer. Overall, epithelial ovarian
cancer accounts for 4% of all new cancer diagnoses and 5%of all cancer related death.
Risk factors for EOC are essentially reproductive and genetic in nature.
High risk : never had children are twice as likely to develop this disease, low parity.
Lower risks: first pregnancy at an early age, early menopause and the use of oral
contraceptives have been associated with lower risks of ovarian cancer.
EOC is a clonal disease that arises from a single cell in more than 90% of cases.
Multiple genetic changes must occur in the ovarian surface epithelium (OSE) to
produce malignant transformation. Repeated rupture and repair (ovulation) of the
OSE provides this opportunity for genetic aberrations. Hereditary factors are
implicated in approximately 5% of all ovarian cancers. So far, the syndromes that
have been identified are:
1. The Breast-Ovarian Cancer Syndrome, linked to an inherited mutation in the
BRCA 1 and the BRCA 2 genes (site-specific Ovarian Cancer Syndrome);
2. Type II Lynch Syndrome, which also includes colon, breast, endometrial and
prostate cancer in affected individuals.

II. Histopathological Classification

Majority of ovarian cancer is of the epithelial origin. The task forces of FIGO endorse
the histological typing of epithelial ovarian tumours as presented in the WHO
publication in 1971. It is recommended that all ovarian epithelial tumours be
subdivided according to a simplified version.

Epithelial ovarian neoplasms are classified as follows:

• Serous tumours
• Mucinous tumours
• Endometrioid tumours
• Clear cell tumours
• Brenner tumours
• Undifferentiated carcinomas

This group of malignant tumours is of epithelial structure but they are too
poorly differentiated to be placed in any other group.

  20  
 • Mixed epithelial tumours
These tumours are composed of two or more of the five major cell types of
common epithelial tumours. The types are usually specified.

Cases with intraperitoneal carcinoma in which the ovaries appear to be incidentally

involved and not the primary origin should be labelled as extra-ovarian peritoneal
carcinoma.
Epithelial tumours of the ovary are also further subclassified by grading.
This is important because histological grading is proportional to prognosis.
This grading system does not apply to non-epithelial tumours.
• Gx – Grade cannot be assessed
• G1 – Well differentiated
• G2 – Moderately differentiated
• G3 – Poorly differentiated

Non-epithelial malignancy, although more uncommon, is also extremely important.

These include granulosa cell tumours, germ cell tumours, sarcomas and lymphomas.
They shall be discussed as separate entities.

III. FIGO Stage ( 2009 )

FIGO TNM
Primary tumour cannot be assessed TX

0 No evidence of primary tumour T0

I Tumour confined to ovaries T1

IA Tumour limited to one ovary, capsule intact T1a

No tumour on ovarian surface
No malignant cells in the ascites or peritoneal washings

IB Tumour limited to both ovaries, capsules intact T1b

No tumour on ovarian surface
No malignant cells in the ascites or peritoneal washings

IC Tumour limited to one or both ovaries, with any of the following: T1c
Capsule ruptured, tumour on ovarian surface, positive
malignant cells in the ascites or positive peritoneal washings

II Tumour involves one or both ovaries with pelvic extension T2

IIA Extension and/ or implants in uterus and/or tubes T2a

No malignant cells in the ascites or peritoneal washings

IIB Extension to other pelvic organ T2b

No malignant cells in the ascites or peritoneal washings

  21  
 IIC IIA/B with positive malignant cells in the ascites or positive T2c
peritoneal washings

III Tumour involves one or both ovaries with microscopically T3

confirmed peritoneal metastasis outside the pelvis and/or and/or
regional lymph nodes metastasis N1

IIIA Microscopic peritoneal metastasis beyond the pelvis T3a

IIIB Macroscopic peritoneal metastasis beyond the pelvis 2 cm or less T3b

in greatest dimension.

IIIC Peritoneal metastasis beyond pelvis more than 2cm in greatest T3c
dimension and/or regional lymph nodes and/or metastasis and/or
N1
IV Distant metastasis beyond the peritoneal cavity M1

FIGO Ovarian Cancer Staging ( Effective Jan. 1, 2014 )

FIGO stage Definition

I Tumor confined to ovaries or fallopian tubes
IA Tumor limited to one ovary (capsule intact) or fallopian tube;
no tumor on ovarian or fallopian tube surface; no malignant
cells in ascites or peritoneal washings
IB Tumor limited to both ovaries (capsules intact) or fallopian
tubes; no tumor on ovarian or fallopian tube surface; no
malignant cells in ascites or peritoneal washings
IC Tumor limited to one or both ovaries or fallopian tubes, with
any of the following:
IC1 Surgical spill
IC2 Capsule ruptured before surgery or tumor on ovarian or
fallopian tube surface
IC3 Malignant cells in the ascites or peritoneal washings
II Tumor involves one or both ovaries or fallopian tubes with
pelvic extension (below pelvic brim) or peritoneal cancer*
IIA Extension and/or implants on uterus and/or tube(s) and/or
ovaries
IIB Extension to other pelvic intraperitoneal tissues

  22  
 III Tumor involves one or both ovaries or fallopian tubes, or
peritoneal cancer, with cytologically or histologically
confirmed spread to the peritoneum outside the pelvis and/or
metastasis to the retroperitoneal lymph nodes
IIIA Positive retroperitoneal lymph nodes and/or microscopic
metastasis beyond pelvis
IIIA1 Positive retroperitoneal lymph nodes only (cytologically or
histologically proven)
IIIA1(i) Metastasis up to 10 mm in greatest dimension
IIIA1(ii) Metastasis more than 10 mm in greatest dimension
IIIA2 Microscopic extrapelvic (above the pelvic brim) peritoneal
involvement, with or without positive retroperitoneal lymph
nodes
IIIB Macroscopic peritoneal metastasis beyond pelvis up to 2 cm
in greatest dimension, with or without positive retroperitoneal
lymph nodes
IIIC Macroscopic peritoneal metastasis beyond pelvis more than 2
cm in greatest dimension (includes extension of tumor to
capsule of liver and spleen without parenchymal involvement
of either organ), with or without positive retroperitoneal
lymph nodes
IV Distant metastases excluding peritoneal metastases
IVA Pleural effusion with positive cytology
IVB Parenchymal metastases and metastases to extra-abdominal
organs (including inguinal lymph nodes and lymph nodes
outside the abdominal cavity)

* Dense adhesions with histologically proven tumor cells justify upgrading to stage II.

  23  
IV. Diagnosis Procedures
A. Medical history (risk factor, history of cancer in the family)
B. Clinical :
- Physical examination ( including breast, pelvic exam, and rectal examination)
- Pap smear if needed

C. Imaging :

- USG ( abdomen- pelvis)

- CT scans ( whole abdomen)
- Chest X-rays / CT scan thorax ( if indicated)
- Colonoscopy ( if bowel involved ).

D. Laboratory :

-­‐ Complete blood count

-­‐ RFT ( BUN, Serum creatinin → hitung Clearance creatinine )
-­‐ LFT ( SGOT, SGPT, Bilirubin direct dan total )
-­‐ Electrolyte (Na,K,Cl,Mg)
-­‐ Albumin
-­‐ CA 125 / HE4
-­‐ CEA ( Carcino-Embrionic Antigen )
-­‐ AFP, LDH and hCG quantitative ( for younger patients /less
than 30 yrs )

E. RMI ( Risk of Malignancy Index)

Criteria Scoring system

Menopausal status (A)
Premenopause 1
Menopause 3

Ultrasound features (B)

Multiloculated No feature : 0
Solid areas 0ne feature: 1
Bilateral >1 feature : 3
Asites
Metastases

Serum CA 125 (C) Absolute level

Risk of Malignancy Index (RMI) AxBxC
RMI > 200 : suspicious for ovarian cancer

  24  
V. Therapy
( appendix )

Adnexal mass

Exclude non-
Gynecological problems
*Pelvic Ultrasound
If necessary, e.g., *CA125
colonoscopy *Calculate RMI

RMI  >200   RMI  <  200  

 

Gynecologist Gynecologist
oncologist

Laparotomy and Individualize

frozen treatment
Section diagnosis Surgery if indicated

Benign Borderline Invasive

Ovarian tumor ovarian cancer

Individualize Limited surgical Full surgical

staging staging

  25  
 MANAGEMENT OF OPERATED PATIENTS
( REFERRED / NOT FULLY STAGED )

  Ovarian Cancers, no residual tumor?

  Not fully staged
 
 

Staging Procedure

Laparotomy/ Laparoscopy

FULL SURGICAL STAGING

• Midline incision (extended incision)

• Careful evaluation of all peritoneal surfaces
• Peritoneal fluid should be sent for cytology.
• Asites (-) → washings of the peritoneal cavity: diaphragm, right and
leftabdomen, pelvis
• Infracolicomentectomy
• Selected lymphadenectomy of the pelvic and para-aortic lymphnodes *
• Biopsy and/or resection of any suspicious lesions, masses and anyadhesions
• Random blind biopsies of normal peritoneal surfaces, includingthat from the
undersurface of the right hemidiaphragm, bladderreflection, cul-de-sac, right
and left paracolic recesses, and bothpelvic sidewalls
• TAH-BSO
• Appendectomy for mucinous tumors

* If chemotherapy is already considered needed, lymphadenectomy is not necessary,

unless enlarged.
 

  26  
 MANAGEMENT OF EARLY STAGE

Early Stage
(stage I-II A presumed preoperatively)

Debulking / oovorectomy
(exploratory laparotomy)

Frozen Section

Benign Borderline Malignant

Close & Wait Careful evaluation of all COMPLETE SURGICAL STAGING

for Parafin peritoneal surfaces.
Coupe Excision & biopsi of all • Midline incision (extended incision)
implants. • Careful evaluation of all peritoneal
Contralateral ovarectomy surfaces
( unless fertility is • Peritoneal fluid should be sent for
considered). cytology.
Close & wait for paraffin • Asites (-) washings of the
coupe peritoneal cavity.
• Selected lymphadenectomy of the
pelvic and para-aortic lymphnodes
• Biopsy and/or resection of any
suspicious lesions, masses and
anyadhesions
• Random biopsies of normal
peritoneal surfaces, includingthat
from the undersurface of the
For fertility sparing surgery: prevesical, Douglas pouche, right
-­‐ Stage IA only, G1-2 and left paracolic recesses, bothpelvic
-­‐ Complete staging ( without TAH) sidewalls,anddiaphragm.
-­‐ Biopsy of contralateral ovary ( if necessary) • TAH-BSO
-­‐ Wait the PA result à reopen if necessary • Infracolic omentectomy
( discuss with the patient ) • Appendectomy for mucinous tumors
 

  27  
 MANAGEMENT AFTER SURGERY

Stage Ia, b, ( grade 1-2)

Stage I c (caused by acute spillage) ( grade 1-2)

Follow up, without chemotherapy

1 st yrs: 3 month,
2 nd yrs: 4 month,
Yearly: CT scan.

All others than : Stage Ia, b, ( grade 1-2) and

Stage I c (caused by acute spillage) ( grade 1-2)

Chemotx: 6x Paclitaxel - carboplatin ( every 3 weeks)

Paclitaxel : 175 mg/ m2 ( 3 hours ) Nacl 0,9%
Carboplatin: AUC 6

Follow up

FOLLOW UP: CA 125 EVALUATION

1st yrs: 3 month, Only if there is any
2nd yrs: 6 month, complaints and / or obvious
Annually until 5 yrs recurrent mass.
( without CA 125 and imaging, unless
there is any complaints )

Note : In case of CA 125 is elevated and there isn’t any compliants and / or obvious
recurrent mass -> use Tamoxiphen 20 mg dd ( for at lease 3 months ).

  28  
 MANAGEMENT OF ADVANCED STAGE

Advanced Ovarian Cancer

- Patient medically fit - Patient medically unfit

- No Large effusion - Parenchymal liver or Lung metastases (+)
- No Parenchymal liver metastases - Fixed pelvic tumor and omental cake
metastases

Primary cytoreduction By cytology, FNAB,

laparoscopy, open biopsy

Residual Tumor < 1 cm Residual Tumor > 1 cm Neoadjuvant : Pacli - Carboplatin

3 courses

Pacli – Carbo 6x Pacli – Carbo 3x CT Scan, check CA 125

Stable/ Response Progression Response (+)/ Stable Progression

Palliative care Interval Debulking (4 Experimental

Secondary cytoreductive/ weeks after last chemo) Protocols,
interval debulking Palliative care

Residual Tumor < 1 Residual Tumor > 1 cm

cm
Pacli- Carbo 3x

Response + from Stable from

previous chemo : previous
Pacli- Carbo 3x chemotherapy
Follow up

Intraperitoneal chemotherapy** 2nd line chemo Dose dense*

  29  
 VI. Recurrence

Recurrence > 6 months after last Recurrence < 6 months after last
chemotherapy (Platinum sensitive) chemotherapy (Platinum resistant)

2nd line chemotherapy

Response (+) Response (-)

Pacli – carbo 3x
2nd line chemo Dose dense* Palliative care

Interval Debulking
FOLLOW UP:
1 st yrs: 3 month,
2 nd yrs: 6 month,
Pacli – carbo 3x Annually until 5 yrs

* DOSE DENSE : Second line chemo:

Paclitaxel 90 mg/m2 ( 3 hours)
Carboplatin AUC 4 ( 30 ‘)
Cyclus 1 day 1,8,15
Cyclus 2 day 29, 36, 43
If response (+) : Paclitaxel
Carboplatin 3x (3 weekly)
If response (-) : Palliative
-­‐ Docetaxel - Carboplatin
-­‐ Caelyx ( +/- Carboplatin )
-­‐ Carboplatin single (Neurotoxicity)
-­‐ Paclitaxel single (Allergic for
Carboplatin)
-­‐ Gemcitabine - Carboplatin
-­‐ Cyclophosphamide - Carboplatin
-­‐ Oral Etoposide
-­‐ Topotecan
-­‐ Tamoxifen (Asymptomatic
Recurrence)

Note:
**IP chemotherapy ( HIPEC ) may be considered in low-volume optimally debulked stage II
and stage III patients.

Consider palliative radiation for isolated recurrence.

  30  
 MANAGEMENT TUMORS SUSPICIOUS FOR NON EPITHELIAL
OVARIAN TUMORS
 

Young Female < 30 yrs*

Mass : solid/ cystic ( indicated as NEOC )

Lab: αFP, β hCG, CA 125, CEA, LDH

If the parameters of NEOC is elevated

Laparotomy or
Diagnostic laparoscopy

-­‐ Remove mass only

-­‐ Wait for final pathology

Discussion

* Or fertility wish
 

  31  
 NON EPITHELIAL OVARIAL CANCER

Types :
1. Germ-cell Tumor
2. Sex-cord stromal Tumor
3. Mesenchymal

GERM-CELL TUMORS

I. Introduction

This group of ovarian tumours consist of a variety of histologically different entities that are
all derived from the primitive germ cells of the embryonic gonad.
Malignant germ cell tumours represent a small proportion of all ovarian tumours.

II. Histological Classification

Germ cell tumours

-­‐ Dysgerminoma
-­‐ Endodermal sinus tumour (yolk sac tumour)/ EST
-­‐ Choriocarcinoma
-­‐ Embryonal carcinoma
-­‐ Teratoma:
o Mature
o Imature, G 1-3 dependent of % immature glia tissue

III. Diagnosis Procedures

1. Clinical

The highest incidence of germ cell tumour occurs in the second andthe third decades of life.
It is frequently diagnosed by finding a palpable abdominal mass in a young lady who
complains of abdominal pain.
The symptoms of germ cell tumours in order of frequency:
• Acute abdominal pain
• Chronic abdominal pain
• Asymptomatic abdominal mass
• Abnormal vaginal bleeding
• Abdominal distention

2. Imaging

Ultrasound ( pelvic and abdomen ),

CT scan whole abdomen + chest x-ray/chest CT

  32  
3. Laboratory

• Complete blood count

• RFT ( BUN, Serum creatinin → hitung Clearance creatinin )
• LFT ( SGOT, SGPT, Bilirubin direct dan total )
• Electrolyte (Na,K,Cl,Mg)
• Albumin
• Inhibine A & B ( granulosa cell)

Diagnosis, staging and surgical management

- Germ cell tumours are staged by FIGO the same as EOC ( epithelial ovarian
cancer).
- The treatment is dependent not only on the stage.
- Conservative surgery is standard in all stages of all germ cell tumours.
- By conservative surgery, it means full laparotomy with careful examination and
detailed biopsies of all suspicious area with limited cytoreduction.
- The uterus and the contralateral ovary should be left intact.
- Highly curable with chemotherapy.

  33  
 IV. Therapy

MANAGEMENT OF GERM CELL TUMOR

Surgical management  

Germ Cell ( the Result of Frozen Section) Referred patients with PA result
shows as Germ-cell tumor :
- Stop the surgery unless expected stage Ia -­‐ Review the spesimen
disgerminoma or immature teratoma Ia *
- In case of dysgerminomaàevaluate
contralat ovary Imaging: CT Scan Whole abdomen +
- Carefull documentation of tumor extention Chest X-Ray/CT scan
- Wait for final PA

No adjuvant chemotx if : Residual Tumor (-)

- Dysgerminoma stage Ia Residual Tumor (+)/ (-) PA diagnosis shows
- Immature teratoma stage Others PA findings dysgerminoma or
Ia G1 immature teratoma
G1
 
Adjuvant chemotherapy :
Confirm the stage Ia
All others need adjuvant (staging laparotomy/
chemotherapy: staging laparoscopy)
- with unfavourable
characteristics : 4x BEP
- with favourbale
Follow-up characteristics : 3x BEP
> Stage 1A Stage 1A
confirmed

Follow-up

* limited surgical staging procedures : ** Favourable : ** Unfavourable:

- Midline incission AFP < 1000 AFP > 10.000 µgr/l
- Peritoneal washing B hCG < 5000 βHCG > 50.000 IU/l
- Peritoneal biopsy LDH < 1,5 x upper level LDH > 10 x upper level
- Diafragmatic biopsy Lung metastasis Metastasis : liver, bones,
- Sampling of pelvic and paraaortic brain, mediastinum
lnn
- Omentectomy

  34  
 Note:
Second look laparotomy in case of incompletely debulked immature teratoma is
indicated.
-­‐ Always in case of immature teratoma after initial incomplete removal of
tumor
-­‐ Remove all abnormal tissue
-­‐ Mature glia tissue ( remove because risk of malignant transformation).
-­‐ If again immature glia tissue: second line chemotherapy VIP ( Vinblastine,
Ifosfamide, Platinum )
 

The recommended chemotherapy regimen ( PEB ) is :

- Etoposide 100mg/m2 per day for 5 days

- Cisplatin 20mg/m2 per day for 5 days,
- Bleomycin at 30 IU per day for day 1/8/15
- In case of toxicity, consider EP
- 3 weekly

V. Follow Up :

Germ-cell tumors most recurr < 2 yrs

• 1 yrs
- Markers monthly
- CT abdomen + chest X ray every 3 month

• 2nd yr ( after 2 yrs pregnancy allowed )

- Markers every 3 month
- CT abdomen + chest X ray every 6 month

• 3-5 yrs
- Markers every 6 month

VI. Recurrence :

-­‐ Second line chemotherapy

-­‐ Individualized management

  35  
 SEX CORD-STROMAL TUMORS

I. Introduction

- Granulosa cell tumours account for about 70% of sex-cord stromal tumours,
- 3-5 % of all ovarian neoplasm.
- Types of granulosa cell tumour: the juvenile and the adult type.
- Due to the high oestrogen production, the juvenile type presents with sexual preciosity,
while the adult type may present with postmenopausal bleeding.
- The peak incidence is in the first postmenopausal decade.
- Slowly growing and late recurrence.

II. Histological Classification

Granulosa-stromal cell tumors

Granulosa cell tumor
Adult type
Juvenile type
Thecoma-fibroma group
Thecoma
Fibroma / fibrosarcoma
Sclerosing stromal stromal tumor
Sertoli-stromal cell tumors
Sertoli cell tumor
Sertoli-Leydig cell
Sex cord tumor with annular tubules
Steroid cell tumors
Stromal luteoma
Leydig cell tumor
Steroid cell tumor not otherwise specified

III. Diagnosis Procedures

A. Imaging :

- Ultrasound (pelvic and abdomen)

- CT scan whole abdomen

B. Laboratory :

- Complete blood count

- RFT ( BUN, Serum creatinin → hitung Clearance creatinin )
- LFT ( SGOT, SGPT, Bilirubin direct dan total )
- Electrolyte (Na,K,Cl,Mg)
- Albumin
- Inhibine

  36  
IV. Therapy :
Surgical Treatment:

Surgery:
• TAH + BSO
• Remove all other tumors
• Complete surgical procedure is not indicated
• Lymphadenectomy is not indicated
• Carefull inspection. Granulosa cell tumor recurrs locally in the
abdominal cavity

V. Follow up:

• 1 yr
- Inhibine every 3 month (elevated: CT)
- In case inhibine not available, every 3 month FSH, LH, or CT scan every 6
month

• 2 yr
- Inhibine every 6 month (elevated: CT)
- In case inhibine not available, every 6 month FSH, LH, or CT scan every 12
month

• 3 – life long
- Yearly inhibine (elevated: CT)
- Or gynecologic examination

VI. Recurrence

• Surgery : Remove the tumor everytime recurrs

• Megestrol Acetate
• BEP (low response rate)
• Granulosa cell tumor is radiotherapy sensible (if localized)

Other tipe of sex cord stromal should be treated with surgery and chemotherapy (BEP).

MESENCHYMAL TUMOR

Should be treated with surgery and chemotherapy (epirubicine) → sarcoma-like tumor.

  37  
 MANAGEMENT OF BORDERLINE
MALIGNANCY
 

BORDERLINE *Visual inspection and

OVARIAN TUMOR palpation of abdominal
  cavity, biopsy, preferably
removal of any abnormality
 
Clinical staging*
 
If invasive implant present,
consider chemotherapy or
If fertility conservation considered secondary surgery
  (individualized).
 

Yes No  
 

TAH- **If mucinous, also

One ovary Both ovary involved or BSO** appendectomy
involved** one ovary present**  
   

Salpingo- Cystectomy
oophorectomy  
 
No further follow-up
 
Follow-up : Transvaginal ultrasound, clinical
examination
 

If the patient was referred from other hospital, do review pathological and ask for surgical report.
If any clinical suspicion on residual disease, consider secondary surgery (laparoscopy).
Questions for pathologist: Serous/mucinous?; Micro-invasive/micropapillary?; Implant à invasive/non-
invasive?
 

  38  
 ENDOMETRIAL CANCER
I. Introduction
- Corpus cancer is one of the most frequently occurring female genital cancers.
- The most common gynecologic cancer in Indonesia is cervical cancer, followed by
ovarian and uterine cancer.
- Histopathological report in 2002 revealed :
o cervical cancer : 2,532 cases ( 1st )
o ovarian cancer : 829 cases ( 3rd )
o uterine cancer : 316 cases ( 8th )
II. Histopathological classification

  39  
III. FIGO stage ( 2009 )

IV. Diagnosis Procedures

A. Clinical :
- Physical examination
- Pelvic examination ( inspekulo examination )
- Transvaginal ultrasound ( endometrial thickness )

B. Histology :
-­‐ ECC + Pipelle / D&C ( if the slides are available → review )
-­‐ Hysteroscopy ( if possible )

C. Imaging :
-­‐ X ray of the chest
-­‐ Ultrasound of whole abdomen( kidney, liver, etc )
-­‐ CT scan / MRI ( more than stage I or gr 3 ) to determine lymphadenopathy ( pelvic
and paraaortic ) → if possible.

D. Laboratory :
-­‐ Complete blood count
-­‐ RFT ( BUN, Serum creatinin → hitung Clearance creatinin )
-­‐ LFT ( SGOT, SGPT, Bilirubin direct dan total )
-­‐ Electrolyte (Na,K,Cl,Mg)
-­‐ Albumin
-­‐ Blood glucose
-­‐ CA 125

  40  
 V. Therapy

Stage I ( Endometrioid )
 

Low Risk (Grade 1-2) High Risk (Grade 3)

- Vertical insicion - Vertical insicion

- TAH-BSO - TAH-BSO
- Palpation of lymph nodes plus - Pelvic lymphadenectomy (+/-
sampling if suspicious paraaortic)
- Laparoscopic

Lymph node Lymph node Lymph node (- Lymph node

(-) (+) ) (+)

EBRT Vaginal EBRT

brachytherapy if :
→ 60yrs or
→1/2 myometrial
invasion

Adjuvant therapy ( for the cases without lymphadenectomy) :

Low risk < 50% G1-2 Follow up

Low interm risk >50% G1-2 <60yo
<50% G3
High interm risk >50% G1-2 >60yo Vaginal brachytherapy
<50% G3 ( follow up if not possible )
High risk >50% G3 EBRT + Vaginal Brachytherapy

For high risk : if EBRT is not available , chemotherapy : Paclitaxel – Carboplatin/TAP*

  41  
 Stage II ( Endometrioid )
 

(1) Radical hysterectomy

+ lymphadenectomy (2) Simple hysterectomy (3) Simple hysterectomy
(fit and not obese) + Lymphadenectomy (palliation)

Ly. Node (-) Ly. Node (+) Ly. Node (-) Ly. Node (+) EBRT

Follow Up Follow Up

EBRT + Brachytherapy
(While waiting : chemotherapy* )

Note : if stage II diagnosed after surgery ( accidently ) → EBRT + Brachytherapy

( while waiting : chemotherapy* )
 

* Chemotherapy regimen :
Paclitaxel 175 mg/m2 – Carboplatin AUC 5

Stage III

IIIa Hysterectomy + chemo or EBRT

IIIb No operation : chemo or EBRT (+ brachytherapy** )
Hysterectomy + chemo or EBRT
IIIc1 Hysterectomy + lymphadenectomy pelvic / paraaorta +
IIIc2 chemo/EBRT ( pelvic or pelvic+paraaorta )

** Need more discussion with radiotherapist.

  42  
 Stage IV

Palliation :
Hormonal
Oral MPA (Provera), in the range of 200-800 mg/day,
Megestrol acetate (Megace), 160 mg/day
MPA (Depo-Provera), 400 mg intra- muscularly at weekly intervals
Radiation
Surgery ( hysterectomy, bowel or urologic surgery, etc )
Chemotherapy ( Paclitaxel 175 mg/m2 – Carboplatin AUC 5 or
TAP/CAP for 4-6 courses )

ENDOMETRIAL CANCER DIAGNOSED AFTER SURGERY

Endometrioid   Serous Papillary / Clear

Cell  

Ooverectomy Radiotherapy
(Laparoscopy/ (With the ovaries No Myometrial Myometrial
Laparotomy)   in situ)   Infiltration   Infiltration (+)  

Adjuvant if needed  
Re-Staging   CT CT
Normal   Abnormal  

No Tumor   Tumor   Debulking/Staging  

Follow Up 6x Pacli – Carbo

(± Vaginal brachyterapy) (± Vaginal brachyterapy)

  43  
 SEROUS PAPILLARY
( > 25% components )
CLEAR CELL Surgical staging steps :
  - Peritoneal washing
- TAH
- BSO
- Omentectomy
- Biopsy abdominal cavity
Treated as the same as Ovarian Cancer:
- Sampling lymphadenectomy
Staging Laparotomy/debulking ( less aggressive than in ovarian
 
cancer due to poor prognosis )

No Myometrial invasion Myometrial invasion

(Staging laparotomy (-)) (Staging laparotomy (+))
   

Follow up 6x Pacli–Carbo
( ± vaginal brachytherapy )   ( ± vaginal brachytherapy )  

VI. Follow Up
Vaginal examination
Physical examination ( include supraclavicular node )
Chest x ray
+/- CA 125
For the 1st year → every three month
For the 2nd -→ every 6 month
After that until 5th year → yearly.

  44  
 VII. Recurrence ( Endometrioid )

Recurrence

Local/Vagina Pelvic Distant

No Prior RT Prior RT No Prior RT Prior RT Abdominal Lung

EBRT +/- Surgery EBRT Palliative

Brachytherapy (Pelvic exent)
Palliative

Unifocal Multifocal

Individualized Treatment : 1. Hormonal

Surgery or chemotherapy 2. Chemotherapy
(need more discussion) 3. Palliative

  45  
 VULVAR CANCER
I. Introduction

- Carcinoma of the vulva is an uncommon tumour, representing about 4% of

gynaecologic malignanciesand occurs most frequently in women between
the ages of 65 and 75.
- GOG reported 5-year survival rates of 98%, 85%, 74%, and 31% for
stages I, II, III, and IV, respectively.
- There is no screening test available for vulvar cancer although a number of
precursor lesions are recognised.
- Women who develop a vulvar cancer are at an increased risk of developing
other genital cancers, particularly cervix.

II. Histopathological Classification

Squamous 70 %,
Melanoma 5 %
Basal cell 15 %
Bartholin gland (adenocarcinoma, squamous cell, transitional cell,
adenoid cystic) 2%
Metastatic 2%
Verrucous 2%
Sarcoma 1%
Appendage ( e.g., hidradenocarcinoma) rare.

Histopathologic grades (G).

• Gx – Grade cannot be assessed;
• Gl – Well-differentiated;
• G2 – Moderately differentiated;
• G3 – Poorly or undifferentiated.

III. FIGO stage( revised 2009 )

I Tumor confined to the vulva

IA Lesion ≤ 2 cm in size, confined to the vulva or perineum and with
stromal with invasion ≤ 1mm, no nodal metastasis.
IB Lesion > 2 cm in size, confined to the vulva or perineum and with
stromal with invasion > 1mm, with negative nodes.

II Tumor of any size with extension to adjacent perineal structures ( 1/3 lower
urethra, 1/3 lower vagina, anus ) with negative nodes.

III Tumor of any size with or without extension to adjacent perineal structures
( 1/3 lower urethra, 1/3 lower vagina, anus ) with positive inguinofemiral
lymph nodes.
IIIA Tumor of any size with positive inguino-femoral lymph nodes
(i) with 1 lymph node metastasis ( ≥ 5 mm ), or

  46  
 (ii) 1-2 lymph node metastasis(es) ( < 5 mm )
IIIB (i) 2 or more lymph nodes metastases ( ≥ 5 mm ) or
(ii) 3 or more lymph nodes metastases < 5 mm
IIIC With positive node(s) with extracapsular spread

IV Tumor invades other regional ( 2/3 upper urethra, 2/3 upper vagina ) or
distant structures
IVA Tumor invades in any of the following :
(i) upper urethra and /or vaginal mucosa, bladder mucosa, rectal
mucosa or fixed to the pelvic bone, or
(ii) fixed or ulcerated inguino-femoral lymph nodes
IVB Any distant metastasis including pelvic lymph nodes

TNM
Stage Description
Classification
0 Tis N0 M0 Carcinoma in situ, intraepithelial carcinoma
I T1 N0 M0 Confined to the vulva or perineum; no nodal metastasis
IA T1a N0 M0 Lesions =< 2 cm with stromal invasion, =< 1 mm
IB T1b N0 M0 Lesions > 2 cm in size or stromal invasion, > 1 mm
II T2 N0 M0 Adjacent spread to the lower urethra, the vagina, or the anus ,
no nodal metastasis
III T1,2 N1a,b Tumor confined to vulva or adjacent spread to the lower
N2a,b,c M0 urethra, the vagina, or the anus and positive inguino femoral
lymph nodes
IIIA T1,2 N1a,b M0 One lymph node metastasis >= 5mm or 1-2 lymph node
metastases < 5 mm
IIIB T1,2 N2a,b M0 Three or more lymph nodes < 5mm or 2 or more lymph nodes
>= 5mm
IIIC T1,2 N2c M0 Lymph nodes with extracapsular spread
IVA T1,2 N3 M0 Tumor with fixed or ulcerated lymph nodes
T3 anyN M0 Tumor with spread into upper urethra/vagina, bladder, rectal
mucosa, bone or fixed to pelvic bone
IVB Any T Any N M1 Any distant metastasis, including pelvic lymph nodes

This classification is a combined FIGO and TNM classification

N0, clinical on palpation no nodes
N1, clinical on palpation non suspicious nodes
N2, clinical on palpation suspicious nodes
N3, fixed or ulcerated nodes

  47  
IV. Diagnosis Procedures

A. Clinical :

• Physical examination (special attention for supraclavicular lymph node) and

gynecologic examination (special attention for groin nodes à size, fixed or ulcerated ),
describing primary tumor (size, site, mobility, distance from clitoris, urethra, vagina,
and anus).
• Take picture (photograph with ruler) of the tumor.
• Diagnosis should be confirmed by biopsy prior to definitive treatment. The biopsy
should include some underlying stroma.
• It is preferable not to excise the entire lesion as it makes it more difficult to plan the
definitive excision.
• If the lesion is 2 cm or less in diameter and depth of stromal invasion is < 1 mm on
wedge biopsy, complete excision of the lesion must be undertaken to allow serial
sectioning to properly assess the depth of invasion.

B. Imaging :

• USG of the groin (and pelvis)

• Chest x-ray preoperatively.
• Appropriate imaging to assess extent of disease and nodal status - this may
include modalities such as Ultrasonography, CT or MRI scanning.
• Imaging of pelvic nodes is indicated if the groin is clinically suspicious.
• Biopsy or FNA of clinically suspicious nodes or other metastases where the
result may alter management.
• Sentinel lymphe scintigraphy.

C. Laboratory :

-­‐ Complete blood count

-­‐ RFT ( BUN, Serum creatinin → hitung Clearance creatinin )
-­‐ LFT ( SGOT, SGPT, Bilirubin direct dan total )
-­‐ Electrolyte (Na,K,Cl,Mg)
-­‐ Albumin

  48  
 V. Therapy
Squamous Cell Carcinoma of the
vulva

≤ 2 cm in diameter or ˃ 2 cm in diameter or
≤ 1 mm stromal invasion ˃ 1 mm stromal invasion

Radical local
excision Early vulvar Ca. Advanced vulvar Ca
(Clinically T1,T2) (Clinically T3,T4)

Clinically N0, N1, by Clinically N2, N3 ;

palpation & USG confirmed pathologically

Lateralized tumor Midline CT scan pelvis

RLE + Ipsilateral IFL RLE + Bilateral IFL RLE + Nodal

debulking of groin
and/or pelvis ; if no
CT-scan available
then do
extraperitoneal pelvic
Node negative Node positive exploration

Follow up Re-surgery : contralateral

IFL
See clinically T3, T4
 
± Adjuvant treatment

  49  
 Clinically T3, T4 vulvar cancer

If stoma necessary No stoma necessary

If bulky mobile nodes (+)

Chemoradiation First do nodal Radical vulvectomy +

debulking Bilateral IFL or
Nodal Debulking

Residual disease

See adjuvant treatment

Salvage Radical
vulvectomy ; or including
exenteration

  50  
 Clinically M2, M3 ,
confirmed pathologically

Fixed or ulcerated Mobile

Primary RLE for the tumor +

Chemoradiation Nodal debulking

See adjuvant
treatment

Adjuvant Treatment

Primary tumor
Node involvement
resection margin

<1 mm >1 mm 1 (+) , intracapsular,

All other (+)
resection resection < 5 mm
margin margin

Re-resection or No futher No futher Radiotherapy

radiotherapy treatment for treatment for unilateral or bilateral
(combined RT the lymph primary tumor for groin + pelvis
for groin & nodes
primary if RT
for groin
necessary)

  51  
 MANAGEMENT OF CLINICALLY SUSPICIOUS GROIN NODES

Clinically suspicious nodes

CT scan of pelvic

Resection of macroscopic groin

nodes and frozen section

Positive Negative

Retroperitoneal resection of Inguinofemoral

any macroscopic pelvic lymphadenectomy
nodes seen on CT-scan

Pelvic and groin radiation Two or more Negative nodes

therapy positive nodes or or
extracapsular 1 microscopically
spread positive node

Observation

Note:
Clinically suspicious groin nodes ( palpable, mobile) → USG → if (+) or (suspicious) → FNAB
→ if (+) (histologically) → CT to asses the pelvic node, if enlarge : pelvic node dissection was
planned at the same time with RV and BGND.
 

  52  
 MANAGEMENT OF CLINICALLY OBVIOUS GROIN NODES

Fixed or ulcerated nodes

Surgically resectable Unresectable

Resection of all macroscopic Pre-operative radiotherapy ±

nodes in groin and any chemotherapy
enlarged pelvic nodes on CT

Post-operative resection of
Post-operative radiotherapy macroscopic residual disease
to groins and pelvis

  53  
 MANAGEMENT OF ADVANCED PRIMARY TUMOR *

Locally advanced primary tumour

Tumor resectable without Resection would require stoma

requiring stoma

Radical tumour resection Pre-operative radiotherapy

and chemotherapy

Surgical margins

Positive Close ( < 5 mm) More than 5 mm

Post-operative Consider radiotherapy Observation

radiotherapy

*Treatment should follow dissection of the groins. Groin and pelvic radiation should follow
standard indications.

  54  
 GESTATIONAL THROPHOBLASTIC DISEASE (GTD) AND GESTATIONAL
THROPHOBLASTIC NEOPLASIA (GTN)

I. Introduction

- Before 1969 almost all GTN à fatal

- The only chemo-curable gynecologic cancer
- Histologic verification is not essential for diagnosis
- 9-20% Complete Hydatidiform Mole (GTD) à GTN
- 4% Incomplete Hydatidiform Mole (GTD) à GTN
- Metastatic sites: lung, vagina, brain, liver, kidney
- 60% occurs post molar pregnancy, 30% post abortion, 10% post normal or ectopic
pregnancy
- Placental Site Trophoblastic Tumor (PSTT) à Different classification and
management

II. Histopathological Classification

WHO histological classification

Gestational Trophoblastic Disease

Complete Hydatidiform Mole
Incomplete Hydatidiform Mole
Gestational Trophoblastic Neoplasia
Chorio Carcinoma
Invasive Mole
Placental Site Trophoblastic Tumor

III. FIGO stage ( 2000 )

Stage Description
Stage I Disease confined to the the uterus
Stage II GTN extends outside of the uterus, but is limited
to the genital structure ( adnexa, vagina, broad
ligament ).
Stage III GTN extends to the lungs, with or without
known genital tract involvement.
Stage IV All other metastasic sites

Modified WHO scoring system combined with FIGO staging ( Bagshawe, 2002 )

  55  
 MODIFIED WHO PROGNOSTIC SCORING SYSTEM AS ADAPTED BY FIGO
Score 0 1 2 4
Age < 40 > 40 - -
Antecedent pregnancy Mole Abortion Term -
Interval months from index pregnancy <4 4-7 7-13 >13
Pretreatment serum hCG ( IU/L ) < 1000 < 10.000 < 100.000 > 100.000
Largest tumor size ( incl uterus ) - 3 to <5 cm > 5 cm -
Site of metastases Lung Spleen/kidney GI Liver/brain
Number of metastases - 1-4 5-8 >8
Previous failed chemotherapy - - Single drug Two or more
drugs

A WHO score of 6 or less: Low risk GTN à single agent chemotherapy

A WHO score of 7 or more: High risk GTN à combination chemotherapy

IV. Diagnosis Procedures

A. Clinical :

- History of previous pregnancy, bleeding or excess vomiting in first trimester of

pregnancy
- Physical examination
- Pelvic examination (inspekulo included)

B. Histology :

-­‐ Uterine cavity evacuation (whenever there is no suspicion of GTN)

C. Imaging :

-­‐ X ray of the chest

-­‐ Pelvic ultrasound
-­‐ Ultrasound of the whole abdomen (kidney, liver, etc)
-­‐ Whole body CT scan (whenever there is lung metastases or suspicion of cerebral
metastasis ) ( for High Risk or Persistent Low Risk )
-­‐ Post other pregnancy or on relapse : Pelvic Doppler USS, MRI pelvic, CT
chest/abdomen, MRI brain +/- CT-PET scan.

D. Laboratory :

-­‐ Complete blood count, biochemistry (LFT, RFT) and complete urine count
-­‐ Quantitative β-HCG count
-­‐ Thyroid function test (whenever there is suspicion of hyperthyroid)

  56  
 V. Therapy

GESTATIONAL TROPHOBLASTIC DISEASE

Uterine cavity evacuation (D & C) *   Hysterectomy**

 

Hydatidiform Mole   Chorio Carcinoma / Invasive Mole  

2 Weekly Quantitative β-HCG count  

Decrease of β-HCG   Increase of β-HCG   GTN ****

Normal β-HCG ***  

Low risk GTN   High risk GTN  

6-12 months of contraception (OC)

 

* In case of lung metastases suspicion, rule out other
metastases sites in order to proceed with curretage
Mole evacuation using suction curettage and uterotonica,
proceeded with a careful light sharp curettage
Quantitative β-HCG count were measured at prior and one
day after evacuation of the mole, and then 2 weekly
thereafter
** Hysterectomy does not improve the prognosis, in
exceptional cases where the tumor is confined to the uterus,
hysterectomy can be considered (no fertility desired,
compliance problem)
*** 1 further specimens at 2 weekly interval à monthly
for six months à 2 monthly for six months
**** GTN criteria:
- at least 3 values of persistently elevated β-HCG
plateau (4 weeks), or sequential rise of β-HCG
for 2 weeks
- metastases diagnosed
- post curettage pathological result of Chorio
carcinoma, invasive mole, and Placental Site
Thropoblastic Tumor

  57  
 MANAGEMENT OF LOW RISK GTN  

MTX LD/ HD *   Hysterectomy **  

Decrease of β-HCG   Increase of β-HCG  

Repeat MTX LD/HD***

Normal β-HCG ****   Management of High risk GTN

 

12 months of contraception (OC)  

* MTX LD : Methotrexate 0,4 mg/kg IM for 5 days, every 2 weeks

MTX HD : Methotrexate 1 mg/kg IM every other day for 4 doses with lecovorin 0,1
mg/kg 24 hours after each dose of MTX, every 2 weeks.

In case of MTX intolerance:

- Actinomycin-D LD : Actinomycin-D 12 micrograms/kg IV daily for 5 days, every 2 weeks
- Actinomycin-D HD : Actinomycin-D 1,25 mg/m2, every 2 weeks

** In exceptional cases where the tumor is confined to the uterus, hysterectomy can be
considered (no fertility desired, compliance problem).

*** Quantitative β-HCG count 2 weeks after every chemotherapy.

**** Consolidation course: 2 more courses of chemotherapy

after normal Quantitative β-HCG count.
 

  58  
 MANAGEMENT OF HIGH RISK GTN
 

EMA-CO *  

Decrease of β-HCG   Increase of β-HCG

 
Repeat EMA-CO

EP-EMA****  
Normal β-HCG ***  

12 months of birth control (OC)   Decrease of β-HCG   Increase of β-HCG  

Repeat EP-EMA

Normal β-HCG ***   Individualized Treatment  

12 months of contraception (OC)   -­‐ Consider TAH

-­‐ For brain metastases:
increase MTX to 1 g/m2 or
25-30 Gy radiotherapy or
excisional surgery
-­‐ For liver metastases:
20 Gy radiotherapy
* EMA-CO : Etoposide, MTX with lecovorin rescue and
Actinomycin (day 1&2) and Cyclophosphamide and Vincristine -­‐ BEP (Bleomycin, Etoposide,
(Oncovine) (day 8) Cisplatin )
 

** Quantitative β-HCG count 2 weeks after every chemotherapy

*** Consolidation course : 3 more courses of chemotherapy after

normal quantitative β-HCG count.

**** EP-EMA: Etoposide, MTX with Leucovorin rescue and Actinomycin and Cisplatin

  59  
 MANAGEMENT OF
PLACENTAL SITE TROPHOBLASTIC TUMOR (PSTT)

Uterus only Metastases

Strongly consider TAH EP-EMA or EMA-CO

Consider TAH if there is tumor in uterus

VI. Follow Up

-­‐ Vaginal examination

-­‐ Physical examination (include supraclavicular node)
-­‐ Chest x ray, CT scan, MRI (if there are signs or symptoms of metastases)
-­‐ Quantitative β-HCG count
o For GTD : Quantitative β-HCG count were measured at prior and one day
after evacuation of the mole, and then 2 weekly thereafter, after normal result
à 1 further specimens at 2 weekly interval à monthly for six months à 2
monthly for another six months
o For GTN : Quantitative β-HCG count were measured 2 weeks after each
chemotherapy started à monthly for six months à 2 monthly for another six
months

  60  
 UTERINE SARCOMA

I. Introduction

• Uterine sarcomas are rare tumors that account for approximately 1% of female genital
tract malignancies and 3-7% of uterine cancers.
• The aggressive behavior of most cases is well recognized.
• Their rarity and histopathological diversity has contributed to the lack of consensus
on risk factors for poor outcome and optimal treatment.
• Preoperative diagnosis is frequently unknown.

II. Histologic Classification

Uterine sarcoma
1. Leiomyosarcoma
2. Endometrial stromal sarcoma (low-grade)
3. Undifferentiated sarcoma (high-grade)

Mixed Malignant Tumor:

Carcinosarcoma is considered as metaplastic form of endometrial carcinoma
and treated as poorly differentiated endometrial cancer.

III.FIGO Stage (2009)

Leiomyosarcoma and Endometrial Stromal Sarcoma:

Stage Description

I Tumor limited to the uterus

IA Less than or equal to 5 cm
IB More than 5 cm

II Tumor extends beyond the uterus, within the pelvis

IIA Adnexal involvement
IIB Involvement of other pelvic tissues

III Tumor invades abdominal tissue (not just protruding into the abdomen)
IIIA One site
IIIB More than one site
IIIC Metastasis to pelvic and/or para-aortic lymph nodes

IV
IVA Tumor invades bladder and/or rectum
IVB Distant metastasis

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Adenosarcoma:

Stage Description
I Tumor limited to the uterus
IA Less than or equal to half myometrial invasion
IB More than half myometrial invasion

II Tumor extends beyond the uterus, within the pelvis

IIA Adnexal involvement
IIB Tumor extends to extrauterine pelvic tissues

III Tumor invades abdominal tissue (not just protruding into the abdomen)
IIIA One site
IIIB More than one site
IIIC Metastasis to pelvic and/or para-aortic lymph nodes

IV
IVA Tumor invades bladder and/or rectum
IVB Distant metastasis

Carcinosarcoma:
Carcinosarcoma should be staged as carcinoma of the endometrium.

IV. Diagnostic Procedure

1. Clinical :

• Commonly diagnosed after surgery; minority detected after curettage

• If present, the symptom and sign are:
-­‐ Abnormal vaginal bleeding (56%)
-­‐ Palpable pelvic mass (54%)
-­‐ Pelvic pain (22%)

2. Imaging :

• Vaginal ultrasound
• Chest X-Ray/CT
• CT-scan abdomen, MRI (optional)

3. Laboratory :

• CBC
• LFT/RFT
• CA125
• CEA

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V. Therapy

UTERINE SARCOMA

Surgery :
• TAH+BSO
• Removes only enlarged lymph nodes
• Removes intraabdominal tumor deposites
(Without systematic staging procedure)

Definitive PA

MANAGEMENT OF CARCINOSARCOMA

CARCINOSARCOMA
Treat as G3 endometrial cancer
( full staging procedure )

Stage I Stage II Stage III Stage IV

Follow up Brachythetapy Combination • Chemotherapy

( optional ) chemotherapy individualized
• Palliative

*Note: If early stage carcinosarcoma is diagnosed preoperatively

à consider a systematic lymphadenectomy (to avoid EBRT).
If the full staging procedure is not performed, give pelvic radiation.

EBRT if available, if it is not available

give Chemotherapy 6x :
ü Ifosfamide/paclitaxel
ü Ifosfamide/cisplatin
ü Carbo/paclitaxel

  63  
 MANAGEMENT OF LOW GRADE ESS

LOW GRADE SS

Stage I Stage II Stage III Stage IVa Stage IVb

Radical Not Not Radical - Progesterone Progesterone

radical radical - Surgery

Follow up Progesterone Follow up

Response No response

Follow up Aromatse
Inhibitor, if
not available,
NOTE: give
• Radical : no residual tumor Doxorubicin
• Not radical : residual tumor (+)

Note:
- In individualized cases, the ovaries can be left insitu
(The rate of recurrence might be increased without impact on survival)

  64  
 MANAGEMENT OF LEIOMYOSARCOMA

LEIOMYOSARCOMA

Stage I not Stage II not Stage III Stage Stage IVb STUMP
radical radical IVa

EBRT   EBRT   - Palliative Follow up

- Hormonal
Chemotherapy :
Docetaxel-Gemcitabine or (progesterone)
Doxorubicin

Note :
Radical : no residual tumor
EBRT=Pelvic±para-aortic EBRT
STUMP= Smooth muscle tumors of
uncertain malignant potential

MANAGEMENT OF UNDIFFERENTIATED SARCOMA

( = High grade ESS )

UNDIFFERENTIATED SARCOMA

Stage I Stage II Stage III Stage IVa Stage IVb

Radical Not Not Radical • No residual tumor: - Doxorubicin

radical radical Doxorubicin - Palliation
• Residual tumor (+):
Doxorubicin+
Follow Follow up pelvic EBRT
up EBRT (sequential)

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 MANAGEMENT OF OPERATED PATIENTS

OPERATED PATIENTS
(without BSO)

CT-SCAN

Residual tumor (-) Residual tumor (+)

No surgery -­‐ BSO (Laparotomy/laparoscopy)

only for low-grade ESS
-­‐ All other types : no BSO

V. Follow-Up :

• 1st yrs: 3 monthly à gynecological examination

• 2-5 yrs: 6 monthly à gynecological examination + imaging if indicated

VI. Recurrence :

• ESS :
-­‐ Hormonal treatment
-­‐ BSO in case ovaries are not removed
-­‐ Surgery may be considered if it responses to hormonal therapy

• Others :
In case of resectable metastasis to lung à surgery may be considered

• Disseminated Disease :
-­‐ Undifferentiated sarcoma à Paclitaxel - Carboplatin
-­‐ Leimyosarcoma à Doxorubicin / Ifosfamide or palliative

  66  
 VAGINAL CANCER

I. Introduction

-­‐ Primary vaginal cancer 2-3% of malignant neoplasms of the female genital tract.
-­‐ More than 50% of patients are diagnosed in the seventh, eighth, and ninth decades
-­‐ Squamous cell histology accounts for about 80% of cases.
-­‐ 84% of carcinomas involving the vagina were secondary, usually from the cervix
(32%); endometrium (18%); colon and rectum (9%); ovary (6%); or vulva (6%).
-­‐ Metastatic tumors in the vagina can also occur from non-gynecological sites such as
the urinary bladder, uretra or periuretral glands, and rarely breast or lung cancer.

II. Histologic Classification

Histologic Tipe Percentage

• Squamous cell 82,6
• Adenocarcinoma (including clear cell) 9,6
• Melanoma 3,3
• Sarcoma 3,1
• Undifferentiated 0,6
• Small cell 0,4
• Lymphoma 0,3
• Carcinoid 0,1

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III. FIGO Stage

Note :
-­‐ Tumors in the vagina involving the cervix regarded as cervical cancer.
-­‐ Tumors involving both the vagina and vulva should be classified as vulvar cancer.

IV. Diagnosis Procedures

A. Clinical
-­‐ General physical examination
-­‐ Pelvic examination

B. Histology
-­‐ Biopsy of the tumors
-­‐ Pap smear

C. Imaging
-­‐ Colposcopy
-­‐ Chest X-ray
-­‐ US
-­‐ IVP
-­‐ CT-scan/MRI
-­‐ Cystoscopy
-­‐ Proctosigmoidoscopy

D. Laboratory
-­‐ CBC and biochemistry

  68  
V. Therapy
-­‐ All treatment must be individualized and will vary depending on the stage of disease,
the site of vaginal involvement, and reproductive desire.
-­‐ Surgery has a limited role in the management of patients with vaginal cancer because
of the radicality required to achieve clear surgical margins unless exenterative
procedure is performed.
-­‐ The proximity of the vagina to the bladder, rectum, and uretra limits the dose of
radiation that can be delivered.

MANAGEMENT OF EARLY STAGE

STAGE I

Chemo-radiation* Individualized
surgical treatment

• Radical local excision+nodes

excision*
• Radical histerectomy+upper
vaginectomy+pelvic nodes excision
• Radical histerectomy+total
vaginectomy+pelvic and inguinal
nodes excision

NOTE:
* Depending on the location of the tumors (lower 1/3 vagina), the groin nodes must be
treated (by radiotherapy or surgery)
Chemo-radiation ~ cervical cancer guidelines.

  69  
 MANAGEMENT OF ADVANCED STAGE

STAGE II-IVA

Chemo-radiation* Individualized treatment

Chemotherapy Cisplatin 50 mg/m2

weekly for 5 cycles

Delayed chemoradiation Individualized surgery :

-­‐ Radical hysterectomy + upper
vaginectomy + pelvic nodes
excision.
-­‐ Radical hysterectomy + total
vaginectomy + pelvic and
inguinal nodes excision.
-­‐ Pelvic exenteration + pelvic
lymphadenectomy

NOTE:
* Depending on the location of the tumors (lower 1/3 vagina), the groin nodes must be
treated (by radiotherapy or surgery)
Chemo-radiotherapy ~ cervical cancer guidelines.

STAGE IVB

PALLIATIVE TREATMENT:
• Chemotherapy
• Radiotherapy (for vaginal
bleeding)
• Surgery (for fistulas)

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VI. Follow-Up

• 1st year : every 3 months

nd th
• 2 – 5 years : every 6 months
• > 5th years : every year

VII. Recurrence

RECURRENT
DISEASE

Pelvic recurrent Extra-pelvic

recurrent

• Palliative radiotherapy
No prior Prior radiotherapy or chemo-radiation
radiotherapy • Resection in selected
patients

Chemo-radiation
Central pelvic Pelvic side-wall
recurrent recurrent

• Consideration for pelvic Palliative

exenteration treatment
• Chemotherapy

  71  
Chemotherapy Regimens

A. Cisplatin
Cisplatin as a radio-sensitizing agent ( EBRT + concurrent cisplatin-containing
chemotherapy )
1. Cisplatin 40-50 mg/m2, repeat weekly x 5 cycles
2. Given on Monday or Tuesday in every week of 5 cycles ( 6 hours before radiation )
3. Needs hydration.
4. Premedication : Antiemetic Hesketh level 5.

Cisplatin as neoadjuvant
1. Cisplatin 50 mg/m2 weekly x 4 cycles.
2. Needs hydration
3. Premedication : Antiemetic Hesketh level 5

Cisplatin as adjuvant treatment ( after surgery, while waiting radiation )

1. Cisplatin 75 mg/m2, repeat 3 weekly maximal 2 cycles.
2. Premedication : Antiemetic Hesketh level 5

Cisplatin in recurrent metastatic disease ( as an optional palliative treatment ).

1. Cisplatin 75 mg/m2, repeat 3 weekly.
2. Need to be evaluated every 2 cycles.
3. Premedication : Antiemetic Hesketh level 5

B. Carboplatin
Carboplatin as radio-sensitizing agent ( EBRT + concurrent carboplatin-containing
chemotherapy )
1. Carboplatin AUC 5 repeat weekly x 5 cycles
2. Given on Monday or Tuesday in every week of 5 cycles ( 6 hours before radiation )

C. Paclitaxel - Carboplatin
1. Paclitaxel 175 mg/m2 * IV in 500 mL NS over 3 hours (use non-PVC equipment, in-
line filter)
Carboplatin AUC** x (GFR +25) IV in 250 mL D5W over 30 minutes
2. * an initial dose of 135 mg/m2 is recommended in patients >75 years of age,
with escalation to 155 mg/m2 and then 175 mg/m2 if tolerated.
3. ** use AUC of 6; if extensive prior radiation therapy, use AUC of 5

D. Dose dense Paclitaxel Carboplatin

1. Paclitaxel 90 mg/m2 ( 3 hours)
Carboplatin AUC 4 ( 30 ‘)
2. Cycle I day 1,8,15
Cycle II day 29, 36, 43
3. If response (+) : Paclitaxel Carboplatin 3x (3 weekly)
If response (-) : Paliative

  72  
E. Docetaxel – Carboplatin
1. Docetaxel 75 mg/m2 * IV in 250 mL** NS or D5W over 1 hour
Carboplatin AUC*** x (GFR +25) IV in 250 mL D5W over 30 minutes.
2. * Use 60 mg/m2 if patient has a history of neutropenic complications following
chemotherapy or prior extended field radiotherapy. In patients >75 years of age, begin
at 60 mg/m2, with subsequent escalation to 75 mg/m2 if tolerated.
3. **If dose is 75-185 mg, use 250 mL dilution. If greater than 185 mg, use 500
mL dilution.
4. *** use AUC of 5. If patient has received extensive prior radiation therapy, use
AUC of 4
5. Hypersensitivity reactions to docetaxel are common but it is not necessary to
routinely initiate the infusion slowly. If slow initiation of infusion is needed,
start infusion at 30 mL/h x 5 minutes, then 60 mL/h x 5 minutes, then 120
mL/h x 5 minutes, then complete infusion at 250 mL/h (for 500 mL bag,
continue 250 mL/h for 5 minutes and then complete infusion at 500 mL/h).

F. Gemcitabine – Carboplatin
1. Gemcitabine 800 mg/m2 (maximum dose 2000 mg) on days 1 and 8, IV in NS 250 mL
over 30 minutes
Carboplatin AUC = 5* ( on day 1 only; after gemcitabine ), IV in D5W 250
mL over 30 minutes
2. * May increase to AUC = 6 if interval platelet count ≥ 150
3. Repeat every 3 weeks. Continue for six cycles, or until disease progression or
intolerable toxicity occurs.

G. Bleomycin – Etoposide – Platamin ( Cisplatin )

1. Etoposide 100mg/m2 per day for 5 days IV in 500 mL NS 30-60 minutes
Cisplatin 20mg/m2 per day for 5 days, in 100 mL NS over 30 minutes
Bleomycin at 30 IU per day for day 1/8/15, IV in 50 mL NS over 10-15 minutes
2. Repeat every 3 weeks.
3. Give treatment on 5 consecutive days.
4. Bleomycin: may cause severe and life threatening pulmonary toxicity. Limiting the total
dose 270 units should decrease the risk but clinical assessment before each cycle must
include a careful survey of respiratory symptoms, chest auscultation, and chest
radiograph for pulmonary toxicity. Pulmonary function tests should be repeated in
suspect cases. Febrile reaction can be prevented by hydrocortisone premedication.
Oxygen may precipitate or aggravate bleomycin pulmonary toxicity. The FI O2 must
not exceed 30-40% unless absolutely necessary. The anesthesiologist must be aware of
the bleomycin history before any surgery: an alert bracelet is recommended.

H. Megestrol Acetate
Megestrol Acetate ( Megace ) 160 mg/day

I. Oxaliplatin – 5 FU
1. Oxaliplatin up to 85 mg/m2 q2weeks; or up to 130 mg/m2 q3weeks. Given as a 2-, 4-,
or 6 hr infusion; 6-hr infusions are used most commonly. Administer in a 5% dextrose
IV solution.

  73  
 5-FU 12 mg/kg IV for 4 days, then if no toxicity occurs, give 6 mg/kg IV on day 6, 8,
10 and 12.
2. In combination, 85 mg/m2 IV infusion 2 hours on day 1, q 2 weeks. May need to
reduce dose to 65 mg/m2 IV infusion for neurosensory, GI or hematologic toxicity.
Increasing duration of infusion to 2-6 hours may decreased acute toxicity.

J. MTX Low Dose

MTX LD : Methotrexate 0,4 mg/kg IM for 5 days, every 2 weeks

K. MTX High Dose

MTX HD : Methotrexate 1 mg/kg IM every other day for 4 doses with leucovorin 0,1
mg/kg 24 hours after each dose of MTX, every 2 weeks.

L. EMA-CO
1. Actinomycin 0,5 mg IV in 1-2 minute on day I and II
Etoposide 100 mg/m2 in 250-500 mL 0,9% NS over 30 minutes on day I and II
Methotrexate 100 mg/m2 in 25 mL 0,9% NS or D5W over 5 minutes and continued
with 200 mg/m2 in 1000 mL 0,9% NS or D5W over 12 hours on day I
Folinic acid ( Leucovorin ) 15 mg PO or IM q12h on day II and III beginning 24 hours
after the start of methotrexate, x 4 doses***
Vincristine 0,8 mg/m2 IV in 1-2 minutes on day VIII
Cyclophosphamide 600 mg/m2 IV in 250 mL 0,9% NS over 30 minutes on day VIII.
2. Repeat every 14 days until 2 full cycles post normal βHCG.
3. Premedication : Day I and II : Antiemeic Hesketh level 5, Day VIII : Antiemetic
Hesketh level 3.

M. EP-EMA
1. Etoposide 150 mg/m2 IV in 250-500 mL 0,9% NS over 30 minutes on day I
Cisplatin 75 mg/m2 + 20 mEq KCl in 1000 mL 0,9% NS over 4 hours on day I*
Etoposide 100 mg/m2 IV in 250-500 mL 0,9% NS over 30 minutes on day VIII
and IX
Methotrexate 100 mg/m2 bolus in 25 mL 0,9% NS or D5W over 5 minutes on
day VIII and continued with 200 mg/m2 infusion in 1000 mL 0,9% NS over 12
hours on day VIII**.
Folinic acid ( Leucovorin ) 15 mg PO or IM q12h beginning 24 hours after the
start of methotrexate, x 4 doses***
Actinomycin-D 0,5 mg IV in 1-2 minutes on day VIII and IX.
2. Repeat every 14 days until 2 full cycles post normal βHCG
3. *Cisplatin should be omitted after four completed cycles if therapy continues,
i.e.- maximum of four cycles of cisplatin.
4. ** Monitoring of methotrexate levels done at 24, 48 and 72 hours.
5. ***If methotrexate is dosed for CNS disease i.e. 1000 mg/m2, then folinic
acid should be changed to 30 mg PO/IV q6h x 12 doses beginning 24 hours
after the start of methotrexate.
6. Premedication : Antiemetic Hesketh level 5

  74  
Cisplatin Hydration

Cisplatin Hydration Electrolyte Comments

( mg/m2 ) Additives
> 80 4000 mL NS over 4 KCl 20 mEq inpatient or medical daycare unit
h MgSO4 1 g admission to monitor urine
Mannitol 30 g output
60-80 2000 mL NS over 2 KCl 20 mEq
h MgSO4 1 g
Mannitol 30 g
40-60 1000 mL NS over 1 KCl 10 mEq includes regimens with cisplatin
h MgSO4 0,5 g administered over multiple days
<40 500 mL NS over 30 none includes regimens with cisplatin
min administered over multiple days

Determination of Creatinine Clearance

1. The creatinine clearance is determined by the Cockcroft-Gault formula, which takes into
account age, weight, and serum creatinine.
weight (kg) × (140−age)
Males: Creatinine Clearance (mL/min) = --------------------------------------
72 × serum creatinine (mg/dL)
weight (kg) × (140−age) x 0.85
Females: Creatinine Clearance (mL/min) = --------------------------------------
72 × serum creatinine (mg/dL)

2. The creatinine clearance can also be determined from a timed urine collection.
urine creatinine urine volume
Creatinine Clearance = --------------------------- x -----------------------
serum creatine time

Suggested Cisplatin dose modifications based on clearance creatinine

Creatinine clearance mL/min Cisplatin dose

> 60 100%
45 - 59 75% cisplatin or go to carboplatin option (if
available)
< 45 hold cisplatin or delay with additional IV fluids or
go to carboplatin option (if available)

  75  
Suggested Carboplatin dose modifications based on clearance creatinine

CrCl (mL/min) Starting dose (mg/m2)

> 60 no dose reduction
41-59 250
16-40 200
≤ 15 no information available

Determination of Target Area Under the Curve (AUC)

The area under AUC refers to the area under the drug concentration × time curve, and it
provides a measure of total drug exposure.

A formula for quantifying exposure to carboplatin based on dose and renal function and is as
follows:

Carboplatin Dose (mg) = target AUC (mg/mL × min) × [GFR (mL/min) + 25]

It is important to note that the total dose is in mg and NOT mg/m2. Target AUC is usually
between 5 and 7 mg/mL/min for previously untreated patients. In previously treated patients,
lower AUCs (between 4 and 6 mg/mL/min) are recommended. AUCs > 7 are generally not
associated with improved response rates.

Guidelines for Percentage of Chemotherapy

Platelets Granulocytes (× 106 cells)

> 2.0 1.5–1.99 1–1.49 < 1.0
> 100,000 100.0 75.0 50.0 0.0
50,000–99,000 50.0 50.0 50.0 0.0
< 50,000 0.0 0.0 0.0 0.0

  76  
Guidelines for Chemotherapy Dosage Based on Hepatic Function

Drug Recommended Dose Reduction

Bleomycin No dose reduction is necessary.

Carboplatin No dose reduction is necessary.

Cisplatin No dose reduction is necessary.

Cyclophosphamide Reduce by 25% if bilirubin 3.0–5.0 mg/dL or SGOT > 180 mg/dL.
Omit if bilirubin > 5.0 mg/dL.
Dactinomycin Reduce dose by 50% if bilirubin > 3.0 mg/dL.

Docetaxel Omit if bilirubin > 1.5 mg/dL, SGOT > 60 mg/dL,

or alkaline phosphatase > 2.5 × upper limit of normal.
Doxorubicin Reduce dose by 50% if bilirubin 1.5–3.0
Reduce dose by 75% if bilirubin 3.1–5.0
Omit if bilirubin > 5.0 mg/dL.
Etoposide Reduce dose by 50% if bilirubin 1.5–3.0
or SGOT 60–180 mg/dL.
Omit if bilirubin > 3 mg/dL or SGOT >180 mg/dL.
5-Fluorouracil Omit if bilirubin > 5.0 mg/dL.

Gemcitabine No dose reduction is necessary.

Ifosfamide No dose reduction is necessary.

Leucovorin No dose reduction is necessary.

Megestrol acetate No dose reduction is necessary

Methotrexate Reduce dose by 25% if bilirubin 3.1–5.0 mg/dL or SGOT > 180 mg/dL.
Omit if bilirubin > 5.0 mg/dL.
Oxaliplatin N/A

Paclitaxel No formal recommendation for dose reduction if bilirubin 1.5–3.0

mg/dL or SGOT 60–180 mg/dL.
Omit if bilirubin > 5.0 mg/dL or SGOT > 180 mg/dL.
Tamoxifen No dose reduction is necessary.

Vinblastine No dose reduction if bilirubin < 1.5 mg/dL

Reduce by 50% if bilirubin 1.5–3.0 mg/dL and SGOT 60–180 mg/dL.
Omit if bilirubin > 3.0 mg/dL or SGOT >
180 mg/dL.and SGOT < 60 mg/dL.
Vincristine No dose reduction if bilirubin < 1.5 mg/dL and SGOT < 60 mg/dL.
Reduce by 50% if bilirubin 1.5–3.0 mg/dL and SGOT 60–180 mg/dL.
Omit if bilirubin > 3.0 mg/dL or SGOT >
180 mg/dL.
.

  77  
Guidelines for Chemotherapy Dosage Based on Renal Function

Drug Recommended Dose Reduction

Bleomycin No dose reduction if CrCl > 60 mL/min.

Reduce dose by 25% if CrCl 10–60 mL/min.
Carboplatin No dose reduction if CrCl > 60 mL/min.
AUC dose is modified according to CrCl.
Cisplatin No dose reduction if CrCl > 60 mL/min.
Reduce dose by 50% if CrCl 30–60 mL/min.
Omit if CrCl < 30 mL/min.
Cyclophosphamide No dose reduction if CrCl > 50 mL/min.
Reduce dose by 25% if CrCl 10–50 mL/min.
Reduce dose by 50% if CrCl < 10 mL/min.
Dactinomycin N/A

Docetaxel No dose reduction is necessary.

Doxorubicin No dose reduction is necessary.

Etoposide No dose reduction if CrCl > 50 mL/min.

Reduce dose by 25% if CrCl 10–50 mL/min.
Reduce dose by 50% if CrCl < 10 mL/min.
5-Fluorouracil No dose reduction is necessary.

Gemcitabine No dose reduction is necessary.

Ifosfamide N/A

Leucovorin No dose reduction is necessary.

Megestrol acetate N/A

Methotrexate No dose reduction is necessary if CrCl > 60 mL/min.

Reduce by 50% if CrCl 30–60 mL/min.
Omit if CrCl < 30 mL/min.
Oxaliplatin N/A

Paclitaxel No dose reduction is necessary.

Tamoxifen No dose reduction is necessary.

Vinblastine No dose reduction is necessary.

Vincristine No dose reduction is necessary.

  78