GYNECOLOGIC ONCOLOGY INTERNS’ TEACHING NOTES

Gynecologic Oncology, UP-PGH

(Revised 2010)

CERVICAL CANCER

I. INCIDENCE
• Most common gynecologic malignancy in the Philippines
• Age Standardized Rate = 22.5/100,000
• Age Incidence:
• PGH and Rizal province: between 40 and 60 years old
• Same observation nationwide and worldwide
• Age specific incidence (Rizal province): between 30 and 35 years old

II. RISK FACTORS

1. Multiple sexual partners (>6)
2. Early sexual activity or early coitus (first coitus < 14 years)
3. Promiscuity of either the patient or the husband/partner
4. Early age of first full term pregnancy (< 17 years)
5. Multiparity (>7)
- high parity maintains the transformation zone in the ectocervix facilitating direct
exposure to HPV and other co-factors
- hormonal changes induced by pregnancy modulates the immune response to HPV
and influence risk of persistence and progression
6. History of sexually transmitted infection – HIV
7. HSV and Chlamydia trachomatis infections
- associated with 2 to 3-fold increased risk for cervical cancer
- they act as co-factors for HPV through induction of cervical inflammation
- history of such infection in the sexual partner also increases risk
8. Smoking history
- mechanisms: (1) secretion of cigarette smoke by-products – nicotine – might have
direct mutagenic effect in the cervical epithelium; (2) cigarette smoke by-
products causes reduction in Langerhans cells in cervix, thus decreasing local
immunity to HPV
9. Oral contraceptives – more than 5 years use within the last 10 years is significant
- mechanisms: direct promoting effects of estrogen on the HPV genome – estradiol
promotes transcription of HPV 16 E6,E7
10. No previous screening
11. Low socioeconomic status

TABLE 1. Relative Risk* of Factors Associated with Cervical Cancer

HIV very high

Moderate dysplasia on Pap smear within past 5 years very high
First intercourse at age < 14 years old 3.52
No prior screening 3-10
HPV (depending on subtype) 2.5-3.0
Six or more lifetime sexual partners 2.27
Low socioeconomic class 5
Race (black vs. white) 2.5
Smoking 2
Current smoker (>5 sticks/day) 1.6
Previous smoker of 5 pack years 1.12
 Passive smoker (>3 hours/day) 2.96
OCP use (> 5 years) 1.9
Barrier contraception 0.4

*DEFINITION: The Relative Risk, or Risk Ratio (RR), of a disease is the ratio of the incidence in people
with the risk factor (exposed persons) to the incidence in people without the risk factor (unexposed
persons). The farther the RR is from 1.0, the greater the difference in risk between the two groups.

The transformation zone is in its most active state of cellular transformation during birth,
adolescence and first pregnancy. This zone is the area of the cervix and vagina initially covered
by columnar epithelium. Through metaplasia, there is replacement by squamous epithelium.
Exposure of this cervical zone to carcinogenic factors/events during these active periods may
increase the risk of development of carcinoma in the new squamocolumnar junction.
To date, 77 different genotypes of HPV have been identified and cloned, among which, types 6,
11, 16, 18, 26, 31, 33, 35, 39, 42, 43, 44, 45, 51, 52, 53, 54, 55, 56, 58, 59, 66, and 68 have the
propensity to infect anogenital tissues. Eight HPV types are highly associated with cervical
cancer, namely: 16, 18, 31, 33, 35, 45, 52 and 58.

HPV subtypes: Low risk (HPV 6, 11, 40, 41, 42) – seen in CIN I or condyloma acuminata
Intermediate (HPV 31, 33, 35, 51, 52) – seen in HSIL (CIN II/III)
High risk (HPV 16, 18, 45, 56) – seen in invasive CA

How does HPV cause carcinoma?

The HPV viral genome encodes 6 early open reading frame proteins (i.e., E1, E2, E3, E4, E6, E7),
which function as regulatory proteins, and 2 late open reading frame proteins (i.e., L1, L2),
which make up the viral capsid. The major difference between the low risk and high risk types is
that after infection, the low-risk HPVs are maintained as extrachromosomal DNA episomes,
while the high-risk HPV genome is found integrated into the host cellular DNA. The
recombination event often leaves E6 and E7 directly coupled to the viral promoter and enhancer
sequences, allowing their continued expression after integration. Because E7 binds and
inactivates the Rb protein while E6 binds p53 and directs its degradation, the functional loss of
both p53 and the Rb genes leads to resistance to apoptosis, causing uncensored cell growth
after DNA damage. This ultimately results in progression to malignancy.

III. PRIMARY PREVENTION

• Total sexual abstinence
• Lifetime mutual monogamy
• Consistent and correct use of barrier contraceptives like condoms (for male and
female) and diaphragms
• Vaccination against HPV infection
• Male circumcision

IV. SECONDARY PREVENTION

RECOMMENDED SCREENING (based on 2010 CPG Recommendations)
• When to start screening
Screening should not begin until the patient is 21, regardless of the age of first
intercourse.

• When to discontinue screening

Discontinue cervical cancer screening between 65 years and 70 years of age in
women who have 3 or more negative cytology test results in a row and no abnormal
test results in the past 10 years.
 • Screening after hysterectomy
In women who have had a total hysterectomy for benign indications and have no
other prior history of high grade CIN, routine cytology testing should be discontinued.

Note:
1. Women treated in the past for CIN 2, CIN 3 or cancer remain at risk for persistent
or recurrent disease for at least 20 years after treatment and after initial post
treatment surveillance, and should continue to have annual screening for at least
20 years.
2. For posthysterectomy (for a benign disease) high-risk patients (diethylstilbestrol
(DES) exposure before birth, HIV infection, or a weakened immune system due to
organ transplant, chemotherapy, or chronic steroid use), annual Pap smear is still
recommended to screen for vaginal intra-epithelial neoplasia (VAIN).

• Screening interval
Annual cervical cytology screening for conventional Pap and biennial cytology
screening for liquid based Pap is recommended for women between the ages 21 and
29 years.

Women aged 30 years and above who have had 3 consecutive negative cervical
cytology screening test results and who have no history of CIN 2 or CIN 3, are not HIV
infected, and are not immunocompromised, and were not exposed to
diethylstilbestrol in utero may extend the interval between cervical cytology
examinations to every 3 years.

Note:
1. For high-risk patients (> 1 risk factor), annual Pap smear is recommended.
2. For centers without a cytology unit, annual direct visual inspection with acetic
acid application (VIA) is recommended.

Co-testing using the combination of cytology plus HPV DNA testing is an appropriate
screening test for women older than 30 years.

V. CLINICAL PRESENTATION
A. Early symptoms
• Vaginal bleeding - most important symptom
• Induced by sexual intercourse or internal examination
• Intermenstrual
• Vaginal discharge
B. Late symptoms
• Pelvic/flank pain
• Bone pain
• Urinary disturbances: dysuria, hematuria
• Bowel disturbances: rectal bleeding
• Lower extremity edema
• Signs/symptoms of uremia
• Triad of pelvic wall involvement: sciatic pain, leg edema, hydronephrosis

VI. DIAGNOSIS
Staging of cervical cancer is based on clinical evaluation; therefore, careful clinical
examination should be performed in all cases, preferably by an experienced examiner
and under anesthesia. The clinical staging must not be changed because of subsequent
findings. When there is doubt as to which stage a particular cancer should be allocated,
 the earlier stage is mandatory. The stage of the disease remains clinical even after the
surgery and not changed by intra-operative findings. However, the prognosis and
subsequent management are both altered by findings which reveal a more advanced
disease.

Clinical staging is applied in cervical cancer:

• To facilitate comparison of treatment outcomes among institutions and between
the different modes of therapy
• Ancillary procedures may not be available in all centers
• Skilled surgeons are not present in every center
• Most patients worldwide are not managed primarily with surgery and are treated
with radiotherapy

The following examinations are permitted:

• Palpation
• Inspection
• Colposcopy
• Endocervical curettage
• Hysteroscopy
• Cystoscopy
• Proctoscopy
• Intravenous pyelography
• X-ray examination of the lungs and skeleton
• Suspected bladder or rectal involvement should be confirmed by biopsy and
histologic evidence.
• Conization or amputation of the cervix is regarded as a clinical examination.
Invasive cancers so identified are to be included in the reports.

The following are optional examinations

• Lymphangiography
• Arteriography
• Venography
• Laparoscopy
• Ultrasound
• CT scan
• MRI

They are of value for planning therapy but, because these are not generally available and the
interpretation of results is variable, the findings of such studies should not be the basis for
changing the clinical staging. Fine needle aspiration (FNA) of scan-detected suspicious lymph
nodes may be helpful in treatment planning.

• Minimal requirements for diagnosis

1. Cervical punch biopsy for those with grossly evident tumor
2. Colposcopy and colpo-guided biopsies following investigation of an abnormal Pap smear
3. Pelvic examination including rectovaginal examination

VII. FIGO CLINICAL STAGING FOR CERVICAL CANCER

Cervical carcinoma has its origins at the squamous-columnar junction whether in the
endocervical canal or on the portio of the cervix. The precursor lesion is dysplasia or carcinoma
in situ (cervical intraepithelial neoplasia (CIN)), which can subsequently become invasive
cancer. This process can be quite slow. Longitudinal studies have shown that in untreated
patients with cervical carcinoma in situ, 30% to 70% will develop invasive carcinoma over a
period of 10 to 12 years. However, in about 10% of patients, lesions can progress from in situ to
invasive in a period of less than 1 year. As it becomes invasive, the tumor breaks through the
basement membrane and invades the cervical stroma. Extension of the tumor in the cervix may
ultimately manifest as ulceration, exophytic tumor or extensive infiltration of underlying tissue
including bladder or rectum.
In addition to local invasion, carcinoma of the cervix can spread via the regional lymphatics or
bloodstream. Tumor dissemination is generally a function of the extent and invasiveness of the
local lesion. While cancer of the cervix generally progresses in an orderly manner, occasionally a
small tumor with distant metastasis is seen. For this reason, patients must be carefully
evaluated for metastatic disease.

2009 FIGO STAGING

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 < 5.0 mm with an extension of < 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

Stage II Cervical carcinoma invades beyond the uterus, but not to the pelvic wall or to the
lower third of the vagina (involves upper 2/3 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

Notes about the staging:

• All macroscopically visible lesions — even with superficial invasion — are allotted to stage IB
carcinomas. Invasion is limited to a measured stromal invasion with a maximal depth of 5
mm and a horizontal extension of not > 7 mm. Depth of invasion should not be > 5 mm taken
from the base of the epithelium of the original tissue — superficial or glandular. The depth
of invasion should always be reported in mm, even in those cases with “early (minimal)
stromal invasion” (~1 mm).
• The involvement of vascular/lymphatic spaces should not change the stage allotment.
• As a rule, it is impossible to clinically estimate if a cancer of the cervix has extended to the
corpus. Extension to the corpus should therefore be disregarded. (Endomyometrial invasion
is an important surgico-pathologic prognostic factor)
• A patient with a growth fixed to the pelvic wall by a short and indurated, but not nodular,
parametrium should be allotted to Stage IIB. It is impossible, at clinical examination, to
decide whether a smooth and indurated parametrium is truly cancerous, or only
inflammatory. Therefore, the case should be placed in Stage III only if the parametrium is
nodular to the pelvic wall or if the growth itself extends to the pelvic wall.
• All cases with hydronephrosis or non-functioning kidney are included, unless they are known
to be due to another cause.
• The presence of bullous edema, as such, should not permit a case to be allotted to Stage IV.
Ridges and furrows into the bladder wall should be interpreted as signs of submucous
involvement of the bladder if they remain fixed to the growth at rectovaginal examination.
Finding malignant cells in cytologic washings from the urinary bladder requires further
histological confirmation in order to be considered for Stage IVA.

VIII. CLASSIFICATION OF CERVICAL TUMORS

EPITHELIAL TUMORS (Modified WHO histological classification)
Squamous cell carcinoma
• Microinvasive squamous cell carcinoma
• Invasive squamous cell carcinoma
• Verrucous carcinoma
• Warty (condylomatous) carcinoma
• Papillary squamous cell (transitional) carcinoma
• Lymphoepithelioma-like carcinoma
Adenocarcinoma
• Mucinous adenocarcinoma
• Endocervical type
• Intestinal type
• Signet-ring type
• Endometrioid adenocarcinoma
• Endometrioid adenocarcinoma with squamous metaplasia
• Clear cell adenocarcinoma
• Minimal deviation adenocarcinoma
• Endocervical type (adenoma malignum)
• Endometrioid type
• Serous adenocarcinoma
• Mesonephric carcinoma
• Well-differentiated villoglandular adenocarcinoma
Other epithelial tumors
• Adenosquamous carcinoma
• Glassy cell carcinoma
• Mucopeidermoid carcinoma
• Adenoid cystic carcinoma
• Adenoid basal carcinoma
• Carcinoid-like tumor
• Small cell carcinoma
• Undifferentiated carcinoma

MESENCHYMAL TUMORS & MIXED EPITHELIAL-MESENCHYMAL TUMORS

• Leiomyosarcoma
• Endocervical stromal sarcoma
• Embryonal rhabdomyosarcoma
• Alveolar soft-part sarcoma
• Adenosarcoma
• Malignant mixed mesodermal tumor (MMMT)

MISCELLANEOUS TUMORS
• Primary malignant melanoma
• Primary choriocarcinoma
• Lymphoma
• Leukemia
• Primary germ cell tumor
IX. MANAGEMENT OF CERVICAL CANCER
A. GENERAL GUIDELINES
• Cervical cancer is diagnosed by biopsy. In the presence of gross lesion, there is no need
for a Papanicolaou smear or a fractional curettage.
• Cervical cancer is staged clinically.
• In selected cases (stage IA2-IB1, IIA1), primary Radical Hysterectomy with Pelvic and
Paraaortic Node Dissection must be performed by a gynecologic oncologist.
• For advanced disease, concurrent chemotherapy and radiotherapy is the minimum
standard of treatment.
- For patients who are unable to receive chemotherapy, radiotherapy treatment alone may
be given.
• Primary total hysterectomy with or without bilateral salpingo-oophorectomy is NOT
performed for a patient with cervical cancer. It is an inadequate surgery and would
mean cutting through tumor. The prognosis is uniformly poor in this situation. Surgical
cure is NOT obtained and the probability of curative radiotherapy is greatly diminished.
• The treatment of cervical cancer requires a multidisciplinary approach involving a
gynecologic oncologist and a radiation oncologist.

B. TREATMENT OPTIONS

1. RADIOTHERAPY – considered as the mainstay of treatment because it can be done to all

stages.
Combined chemotherapy plus radiation therapy for cervical cancer
Five randomized phase III trials have shown an overall survival advantage for cisplatin-
based therapy given concurrently with radiation therapy. The patient populations in
these studies included women with FIGO stages IIB to IVA cervical cancer treated with
primary radiation therapy and women with FIGO stages IA2 to IIA disease found to have
poor prognostic factors (metastatic disease in pelvic lymph nodes, parametrial disease,
or positive surgical margins) at time of primary surgery. Although the trials vary
somewhat in terms of stage of disease, dose of radiation, and schedule of cisplatin and
radiation, they all demonstrate significant survival benefit for this combined approach.
The risk of death from cervical cancer was decreased by 30% to 50% by concurrent
chemoradiation. Based on these results, strong consideration should be given to the
incorporation of concurrent cisplatin-based chemotherapy with radiation therapy in
women who require radiation therapy for treatment of cervical cancer.

Mechanisms of chemotherapy as a radiosensitizer

1. increases the slope of the radiation dose-response rate
2. cell synchronization into the radiosensitive phase of the cell cycle
3. inhibition of repair of sublethal DNA damage
4. decreases tumor bulk thus increasing sensitivity to radiation
5. increases delivery and uptake of radiation

Two stages/phases –
• External Beam Radiotherapy (EBRT)/Teletherapy: Cobalt or LINAC (linear
accelerator). Initial external beam fields encompass a clinical target volume that
includes the primary tumor and adjacent areas at risk for direct occult invasion or
regional lymph node metastases.

Typical regimen (concurrent chemoradiation) would include

• Initial external beam dose of 40-50 Gy to the pelvis in fractions of 1.8-2 Gy given in
25 to 30 days, 5 days per week.
• Cisplatin usually is given weekly at a dose of 40 mg/m2 of body surface area, with a
maximum weekly dose of 70 mg.
• Anemia can be exacerbated by the combined-modality treatment; blood transfusions
commonly are administered to maintain a hemoglobin level of 10-12 g/dL or higher.
• Other toxicities of the combined-modality treatment include electrolyte irregularities
such as hypokalemia, hypomagnesemia, and hypocalcemia. Patients receiving this
treatment should be monitored closely and given electrolyte replenishments when
indicated.

• Internal Radiotherapy/Brachytherapy - Brachytherapy involves the temporary

placement of intrauterine tandem and intravaginal ovoid that are afterloaded with
radioactive material. Device placement is performed under general anesthesia or
heavy sedation. Radiopaque vaginal gauze secures the devices in place and fixes their
relative position to the bladder and rectum. Intraoperative radiographs or digital
fluoroscopic images document appropriate device positioning. Contrast material in a
foley catheter and a rectal tube can be used to aid in identifying the International
Commission of Radiological Units (ICRU) reference points of interest.

International Commission of Radiological Units gynecologic brachytherapy dose

reference points
• Point A - Two centimeters cephalad to the internal os along the tandem and 2 cm
perpendicular to the plane of the tandem (represents dose to the paracervical
triangle)
• Point B - Two centimeters cephalad to the internal os and 5 cm lateral to the
patient’s midline (represents dose to the obturator LN)
• Bladder point - The most posterior point within the foley catheter bulb along a
direct AP line through the bulb’s center
• Rectal point - One half of a centimeter posterior to the vaginal mucosa in the
patient’s midline at the level of the posterior aspect of the ovoid

Brachytherapy may be performed in the form of either HDR (high-dose rate) or LDR
(low-dose rate) applications.
• HDR brachytherapy typically involves 5-7 weekly outpatient procedures in which
the radioactive source is iridium Ir 192 of very high activity. Point A receives a
dose of 5-7 Gy during each treatment, typically accomplished in less than an
hour.
Potential advantages:
• Performed in the outpatient setting
• Uses remote afterloading equipment, eliminating exposure to hospital
personnel
Potential disadvantages
• Theoretical concerns of increased complications due to predicted decreased
therapeutic ratio for a given dose of HDR compared to LDR
• Need to do multiple implants (4 to 6)
• Uncertainty as to what is the best dose & schedule to ensure the best
treatment results with the lowest risk of complications.

• LDR brachytherapy usually involves 1 or 2 placement procedures in which the

radioactive source is cesium Cs 137. Each time, the sources are left in place for
approximately 2-3 days, during which time a dose of 20-40 Gy is administered to
point A.

The total combined external beam and HDR brachytherapy to point A usually is 75-80 Gy,
somewhat lower than the total dose when using LDR brachytherapy. In the latter case,
the biologically equivalent total dose to point A would be 85-90 Gy. The reason for this
difference between doses used in HDR and LDR brachytherapy relates to the anticipated
intracellular radiation repair mechanisms active during the more prolonged LDR
application.
 ADVANTAGES OF RT:
• It can be done for all stages of CCA.
• Appropriate treatment for patients with medical problems and are poor surgical risks.

COMPLICATIONS OF RT:
• During the acute phase of pelvic radiation, the surrounding normal tissues such as the
intestines, the bladder, and the perineum skin often are affected.
• Acute adverse gastrointestinal effects include diarrhea, abdominal cramping, rectal
discomfort, or bleeding. Diarrhea usually is controlled by either loperamide
(Imodium) or atropine sulfate (Lomotil). Small, steroid-containing enemas are
prescribed to alleviate symptoms from proctitis.
• Cystourethritis also can occur, which leads to dysuria, frequency, and nocturia.
Antispasmodics often are helpful for symptom relief.
• Urine should be examined for possible infection. If urinary tract infection is
diagnosed, therapy should be instituted without delay.
• Proper skin hygiene should be maintained for the perineum, and topical lotion should
be used in case erythema or desquamation occurs.
• Late sequelae of radiation usually appear 1-4 years after treatment. The major
sequelae include rectal or vaginal stenosis, small bowel obstruction, malabsorption,
chronic cystitis, radiation proctitis, and fistula formation.

2. SURGERY

RHBLND, PALS – radical hysterectomy with bilateral pelvic lymph node dissection, para-
aortic lymph node sampling (with or without bilateral salpingo-oophorectomy)
• Surgical procedure done for early stage cervical cancers (stage IA2-IB1, IIA1)
• Procedure which includes the removal of the:
- uterus and its ligaments, ligated as close to the pelvic sidewalls as possible
(round, infundibulopelvic, uterosacral, cardinal ligaments);
- the parametria and paracervical tissues;
- upper half of the vagina or as much as 3 cm of the vagina;
- all pelvic lymph nodes (external and internal iliacs, obturator nodes) and para-
aortic lymph nodes

Different types of hysterectomy

Tissue Class I Class II Class III Class IV Class V
Extrafascial Modified radical Radical Anterior/posterior
hysterectomy hysterectomy hysterectomy/ /total
Meig’s-Okabayashi exenteration
Parametria & Remove part of the Removed at level Removed lateral to Same Same
paracolpus parametria of ureters the ureters
Other Reflection and Ureters freed from Ureters are Ureters are Resection of a
structures retraction of the the paracervical dissected from the completely portion of the
removed ureters laterally position but not pubovesical dissected from the distal ureter or
without actual dissected out of ligament pubovesical bladder or rectum
dissection from the the pubovesical ligament with with
ureteral bed; ligament complete removal reimplantation of
clamping of of all periureteral the ureters to the
adjacent tissues, superior bladder (uretero-
paracervical tissues vesical artery is neocystostomy)
w/o cutting into sacrificed
the side of the
cervical tissue;
pubocervical fascia
incised
Cardinal Cut close to the Medial half (medial Up to the pelvic Same Same
ligaments uterus to ureters) sidewall (lateral to
the ureters)
Uterine Ligated at level of Ligated at level of Ligated at origin Same Same
vessels the internal the ureters from hypogastric
cervical os vessels
Uterosacral Ligated at uterus Divided midway to Divided near Same Same depending if
ligaments rectum rectum posterior
exenteration
Vaginal cuff Vaginal rim 1-2 cm removed ≥ 2 cm removed 3/4 of vagina Same
removed (upper third) (upper third)
Indications CIN, CIS, stage 1A1, Stage 1A2, small Stage 1B1 or IIA1 Anteriorly occurring Central
preoperative post irradiation recurrences where recurrences
radiation of recurrences (≤ 2 preservation of the involving portions
adenocarcinoma of cm) bladder is possible of the distal
the cervix or ureters, bladder or
barrel-shaped SCCA rectum

History of the Procedure:

• In 1895, Clark performed the first radical hysterectomy for cervical cancer at Johns
Hopkins; each of his radical surgeries differed.
• In 1898, Wertheim, a Viennese physician, developed the radical total hysterectomy
with removal of the pelvic lymph nodes and the parametrium. In 1905, Wertheim
reported the outcomes of his first 270 patients. The operative morality rate was 18%,
and the major morbidity rate was 31%.
• In 1901, Schauta described the radical vaginal hysterectomy, which had less
operative mortality compared with the abdominal route.
• In the late 19th century, radiation therapy became the favored approach due to the
high mortality and morbidity of the surgical approach.
• Meigs repopularized the surgical approach when he developed a modified Wertheim
operation with removal of all pelvic nodes. Meigs reported a survival rate of 75% for
patients with stage I disease.
• Radical hysterectomy is indicated for patients with stage IA2-IIA cervical cancer who
are medically fit enough to tolerate an aggressive surgical approach and do not desire
to endure the long-term side effects of radiation therapy. Young patients who desire
ovarian preservation and women in whom retention of a functional, nonirradiated
vagina are ideal candidates for this procedure. Patients who have relative or absolute
contraindications to radiation therapy, such as a pelvic kidney, a history of pelvic
abscess or, prior pelvic irradiation, should be afforded surgical management. In the
recurrent setting, radical hysterectomy has been performed for very small centrally
recurrent or persistent disease after radiation therapy. Radical hysterectomy also is
indicated for other disease processes, such as primary upper vaginal carcinoma and
endometrial cancer that involves the cervix.

TECHNIQUE OF THE SURGICAL PROCEDURE:

1. The entire abdomen and pelvis are explored in a systematic fashion to evaluate for
any palpable evidence of disease spread beyond the cervix. Locally, the peritoneal
surfaces anterior and posterior to the cervix are carefully inspected and palpated.
The uterus, fallopian tubes, ovaries, and upper abdomen are carefully inspected for
evidence of gross disease.
2. The paravesical and pararectal spaces are opened, which allows better palpation of
the parametrium for evidence of disease.
3. Next, the bladder flap is taken down. Caution should be taken in this endeavor, as an
adherent bladder flap may be an indication of tumor invading through the cervix and
into the bladder. If this is discovered, consideration must be given to termination of
the procedure in order to give the patient the best chance at a cure.
4. Next, the uterine artery is isolated from its origin at the internal iliac artery. This
can be identified by finding the superior vesical artery and tracing it back to the
hypogastric artery. The uterine artery is ligated. The uterine vein also can be
 identified and ligated to avoid bleeding during the remainder of the parametrial
dissection.
5. The ureter is dissected out from the parametrium. After dissecting out the ureters
from the tunnel and moving the bladder down a couple of centimeters below the
cervix, the posterior dissection is performed.
6. The rectovaginal space usually can be dissected with blunt dissection directly in the
same plane as the vagina (i.e., toward the patient’s feet). The peritoneum is freed
bilaterally from the uterosacral ligaments.
7. The uterosacral ligaments can then be divided to define the posterior-most boundary
of the dissection.
8. The cardinal ligaments are then clamped, divided, and ligated at the pelvic sidewall.
9. If the ovaries are to be removed, the infundibulopelvic ligament is clamped, ligated,
and divided. In most premenopausal patients, the ovaries do not need to be removed
since the risk of disease metastasis to the ovary with squamous carcinomas and
adenocarcinomas is about 0.5% and 1.5%, respectively.
10. The parametria then is taken from its inferior attachments with multiple lateral-to-
medial clamps until the vagina is reached.
11. A 2-cm margin of vaginal cuff around the cervix is recommended, although this tissue
does retract somewhat after being transected from its natural attachment to the
vagina.
12. The pelvic lymphadenectomy is performed in a systematic fashion. The anatomy of
this procedure involves stripping all fatty tissue off of the midportion of the common
iliac vessels, the internal and external iliac vessels to the level of the circumflex iliac
vein distally, with preservation of the genitofemoral nerve on the psoas muscle. The
nodal tissue in the obturator fossa is removed from above the obturator nerve to the
external iliac vein superiorly and laterally to the pelvic sidewall.
13. Careful attention to hemostasis upon completion of the operation is essential to
prevent postoperative hematoma and its associated complications.

ADVANTAGES of surgery:
• Treatment is immediate and short, done in one sitting.
• Sexual function is maintained by preventing synechiae formation and stenosis of the
vaginal canal when instituting RT. Surgery decreases the functional length of the
vagina, but the pliability and transudative lubrication is maintained.
• Ovaries can be transposed and preserved in young patients.
• Intra-operative evaluation of the extent of the disease and identification of
surgicopathologic factors are possible.
• Psychologic relief and improved sense of well-being of the patient that the bulk of
the tumor has been removed.

Contraindications:
• patients who are medically infirm
• those who refuse surgical management
• patients whose religious or personal beliefs prohibit blood product transfusion, since
between one third and two thirds of patients require transfusion. Radiation therapy
should be considered for these patients

Complications from surgery:

Intraoperative
• Injuries to pelvic structures: ureters, bladder, pelvic vessels, nerves and adjacent
organs
• Hemorrhage and subsequent need for transfusion
• Anesthetic complications
 Early post-operative
• Bladder complications: overflow incontinence, urinary retention, loss of bladder
sensation, and detrusor instability occur due to bilateral disruption of
parasympathetic and sympathetic nerve fibers of the bladder and ureter.
• Infection: UTI, psoas/pelvic abscess, pelvic cellulitis
• Surgical wound complications: seroma and hematoma that lead to wound skin
separation, wound abscess, and wound dehiscence. (Poor healing due to comorbid
illnesses such as obesity, steroid dependence, chronic obstructive pulmonary disease
(COPD), and poor preoperative nutritional status can significantly contribute to
increased risk of wound complications.)
• Ureteral stricture and fistula – ureter may be devitalized significantly during the
dissection
• Ileus
• Rectal dysfunction manifested by abnormal internal sphincter relaxation, decreased
rectal sensation, and increased abdominal pressure required to produce a bowel
movement rarely are reported, although these conditions may be the result of
disruption of autonomic sensory nerves
• Venous thrombosis, pulmonary embolism
• Lymphocyst
• Ureterovaginal fistula, vesicovaginal and rectovaginal fistulas

Late post-operative
• Sexual dysfunction due to foreshortened vagina
• Lymphedema
• Stricture and fibrosis of the intestine or rectosigmoid colon
• Small bowel obstruction due to postoperative adhesion formation
• Bladder dysfunction

The Foley catheter is maintained for 3 weeks post-operatively to prevent bladder atony and
urinary stasis. Dissection during the surgery leads to disruption of the parasympathetic and
sympathetic nerves to the bladder. Two patterns of dysfunction are seen: Hypertonic (more
common) and hypotonic. Ureteral pressure is increased in the hypertonic bladder resulting
in difficulty in voiding. In the hypotonic bladder, vesical pressure builds up leading to
distention. Both are self-limiting but less so in the hypotonic pattern where intermittent
catheterization/suprapubic cystostomy may eventually be needed

Carcinoma: Clinical Practice Guidelines Summary

STAGE STATUS TREATMENT

1. Desirous of pregnancy, (-) Lymphovascular
Space Invasion (LVSI)
a. negative margins – observe1 [Level 1b]
b. positive margins - repeat cone biopsy1 [Level
1b]
2. Not desirous of pregnancy, (-) LVSI
Stage 0*
Good surgical a. Extrafascial hysterectomy (EH) with or
Stage IA1*
risk without bilateral salpingo-oophorectomy (±
BSO)8 [Level 1b]
b. Vaginal extrafascial hysterectomy ± BSO 8
[Level 1b]
3. (+) LVSI: Modified Radical Hysterectomy (mRH)
+ BSO with Bilateral pelvic Lymph Node
Dissection (BLND) (ref) [Level 2b]
 Intracavitary Radiotherapy (Brachytherapy): High
Poor surgical
Dose Rate (HDR) or Low Dose Rate (LDR)
risk
(if positive LVSI: pelvic EBRT + brachy)
1. Desirous of pregnancy, (-) LVSI
Radical trachelectomy (Dargent) and
Good surgical extraperitoneal
risk or laparoscopic lymphadenectomy9, [Level 2b]
Stage IA2*
2. Not desirous of pregnancy
mRH, BLND ± BSO10 [Level 1b]
Poor surgical Pelvic External Beam Radiotherapy (EBRT)** +
risk Brachytherapy [Concurrent chemoradiation]
1. Radical Hysterectomy (RH), BLND ± Paraaortic
lymph node sampling (PALS) ± BSO11,12 [Level
Good surgical 1a]
risk 2. Concurrent Chemoradiation13,14 [Level 1a]
Stage IB1 , IIA1 3. Radical Vaginal Hysterectomy (Schauta) ± BSO
and extraperitoneal or laparoscopic
lyphadenectomy [Level Ic]
Poor surgical
Concurrent Chemoradiation 13,14 [Level 1a]
risk
1. Concurrent Chemoradiation*** 4,22,23,24 [Level 1b]
2. RHBSO-BLND ± PALS, which usually needs to be
followed with adjuvant chemoradiation1,17,25
(type of radiotherapy will be dependent on the
surgico-pathologic factors) [Level 2b]
3. Neoadjuvant chemotherapy (three rapidly
delivered courses of platinum-based
chemotherapy), followed by RHBSO-BLND ± PALS
+ adjuvant post-operative radiation or
Stage IB2, IIA2
chemoradiation26,27 [Level 1b]. Chemotherapeutic
options include:
a. Cisplatin-Vinblastine-Bleomycin (PVB)
b. Cisplatin-Bleomycin (PB)
c. Cisplatin-Ifosfamide
d. Cisplatin-Paclitaxel
e. Cisplatin-Irinotecan
4. Concurrent chemoradiation followed by RHBSO
with selective pelvic & paraaortic
lymphadenectomy (Level 2b)
Concurrent Chemoradiation 2,3,4,5,7,15,16 [Level 1a]
Paraaortic lymphadenopathy (size > 1.0 cm) by MRI
or CT scan confirmed by FNAB or extraperitoneal
or laparoscopic lymphadenectomy:
Stage IIB - IV Extended Field Radiotherapy (EFRT) + concurrent
chemotherapy + brachytherapy [Level 2a]
If with evidence of distant metastases on imaging
and/or biopsy:
Systemic combination chemotherapy and
individualized radiotherapy [Level 2a]
X. PROGNOSIS

FIGO Report 5-year survival rate

Stage 5-year Survival Rate
I 85%
II 66%
III 39%
IV 5%

XI. SPECIAL SITUATIONS

A. Adjuvant, post-operative radiotherapy

Adjuvant, post-operative radiotherapy is recommended for patients whose primary therapy
was surgical, but whose surgical specimen revealed unfavorable prognostic features

The Following are unfavorable/poor prognostic factors:

• Tumor size of more than 2 cms
• Cervical stromal invasion of more than 1/3
• Positive lines of surgical resection
• Lymph node metastasis
• Lymphovascular space invasion
• Endomyometrial invasion
• Biopsy-confirmed abdominal metastasis

PROGNOSTIC FACTORS ADJUVANT TREATMENT

(ref)
1. Tumor size > 2 cm Concurrent chemotherapy and pelvic EBRT
[Level 2b]
2. Greater than 1/3 stromal Concurrent chemotherapy and pelvic EBRT17,18
invasion [Level 2a]
3. Positive lines of resection Parametrium Concurrent chemotherapy
and pelvic EBRT6 [Level 1B]
Surgical margins Concurrent chemotherapy
(ref)
and pelvic EBRT [Level
1B]
Vaginal cuff or < 2 cm Concurrent chemotherapy,
tumor free margin pelvic EBRT and
brachytherapy [consensus-
based]
4. Lymph node metastasis Pelvic Concurrent chemotherapy
and pelvic EBRT6 [Level 1b]

Note: If para-aortic
sampling not performed,
may do EFRT if MRI or CT
Scan confirms periaortic
lymphadenopathy.
Para-aortic and Concurrent chemotherapy
Common iliac and EFRT15,16 [Level 2a]
5. Lymphovascular space Concurrent chemotherapy and pelvic EBRT17 [Level
invasion (LVSI) 2a]
6. Endomyometrial invasion Concurrent chemotherapy and pelvic EBRT19 [Level
C]
7. Biopsy proven abdominal Systemic chemotherapy and individualized
 metastasis radiotherapy [Level 2a]

B. Incidentally diagnosed invasive cervical cancer.

Patients who have had a hysterectomy, where the specimen reveals an unsuspected invasive
carcinoma of the cervix, initial diagnostics include: slide review, Chest X-ray,
Abdominopelvic CT Scan, MRI or PET Scan, Liver function tests, Renal function tests and If
tumor size > 4 cms: cystoscopy/proctosigmoidoscopy

Pathologic Review Result Recommended Treatment(s)

Stage 1A1 with no LVSI Observation [Level 2a]
Chemoradiation [Level 2a]
Stage 1A1 with LVSI, Stage 1A2 and Stage IB1 Complete parametrectomy with pelvic
Negative margins & negative imaging studies lymphadenectomy +/- paraaortic lymph node
sampling [Level 2a]
Stage 1A1 with LVSI, Stage 1A2 and Stage IB1 Chemoradiation (ref) [Level 2a]
Positive margins, gross residual disease If paraaortic lymph node positive: give EFRT
(ref)
and/or positive imaging studies [Level 2a]

C. Invasive carcinoma during pregnancy

Age of Gestation Early Stage (Stage I – Late Stage ( Stage IIB – IV)
IIA)
Good surgical risk
Early Pregnancy RHBLND ± BSO 54 Chemoradiation54
up to 20 weeks AOG Poor surgical risk
Chemoradiation 54
May delay treatment
20-28 weeks AOG Chemoradiation
till after delivery
Late Pregnancy
54
After 28 weeks CS* followed by Chemoradiation
Good surgical risk
* Perform Cesarean CS* – RHBLND ± BSO 54 OPTION: Antepartal chemotherapy until 2
Section (CS) at best weeks prior to CS*
time of fetal survival

D. Recurrent cervical cancer

PELVIC
With prior surgery, no prior radiotherapy Chemoradiation (ref) [ Level 2a]
With prior radiotherapy, central disease with Appropriate surgery (EH or MRH) may be
tumor size ≤ 2 cm performed 28,29,30,31,32 [Level C]
(if adverse surgicoprognostic factors are
present, adjuvant chemotherapy should be
instituted)
With prior radiotherapy, central disease with Platinum-based chemotherapy or best
tumor size > 2 cm and noncentral disease supportive care
With prior chemoradiation, central disease Nonplatinum-based chemotherapy or best
with tumor size > 2 cm and noncentral supportive care
disease

EXTRAPELVIC OR PARAAORTIC
Multiple sites, unresectable Systemic chemotherapy or best supportive
care [Level 2a]
Isolated site Tumor resection [Level 2a]
Tumor directed radiotherapy [Level 2a]
Systemic chemotherapy or best supportive
 care [Level 2a]
E. Cervical stump carcinoma
If early stage cervical disease is noted, radical surgical removal with parametriectomy,
upper vaginectomy, bilateral pelvic lymphadenectomy and para-aortic lymph node sampling
is the treatment of choice. For more advanced disease or late stage disease, chemoradiation
is generally preferred.

F. Disseminated cervical cancer

The treatment for disseminated cervical cancer primarily is palliative in nature because cure
is not possible.
• Chemotherapy with single agents such as cisplatin or ifosfamide results in response rates
of approximately 20%. Combination regimens have higher response rates and can prolong
disease-free survival. However, toxicity is increased and no survival advantage is gained.
In addition, the duration of response usually is short.
• Palliative radiation often is used individually to control bleeding, pelvic pain, or urinary
or partial large bowel obstructions from pelvic disease.
• Invasive procedures such as nephrostomy or diverting colostomy sometimes are
performed in this group of patients to improve their quality of life.
• Special effort should be made to ensure comprehensive palliative care, including
adequate pain control for these patients.
ENDOMETRIAL CANCER
I. INCIDENCE
• 75% occur in women 50 years and older, and 95% occur in patients over 40 years old
• peak age is sixth to seventh decade of life, with average age of onset at 60 years old
• less than 5% occur in women < 40 years old
• 3rd most common genital tract malignancy in the Philippines next to cervical and
ovarian cancers which rank first and second, respectively
• Ranks 17th among malignancies affecting both sexes and 8th among females
• More common in developed countries

II. PREDISPOSING FACTORS

Unopposed estrogen 2-10x

Obesity 2-4x
overweight 1.6x
obese 3.88x
Polycystic ovarian syndrome, chronic anovulation 3x
Nulliparity 2x
- With infertility 8x
Early menarche (< 10 years) 3x
Late menopause (> 55 years) 2x
Feminizing ovarian tumors 10x
Use of drug Tamoxifen (more than 2 years) 2.53x
Other related medical disease
- hypertension 1.5x
- diabetes mellitus 2x
Personal or family history of cancer of breast or colon 22-55%
(e.g. hereditary nonpolyposis colorectal cancer)
Atypical hyperplasia 29%
Combinations OCPs 0.5

Explanation of some risk factors:

1. obesity
- in premenopausal women : obesity causes insulin resistance, ovarian androgen excess,
anovulation and decreased circulating progesterone and sex hormone binding globulins –
results in increased circulating free estrogen
- in postmenopausal women: there is peripheral conversion of androgen to estrogen
2. PCOS – chronic anovulation is associated with estrogen excess stimulating hyperplasia of
endometrium
3. hypertension – indirect risk factor, common among elderly and is associated with other risk
factors, such as diabetes mellitus
4. diabetes mellitus – 2 mechanisms: (1) insulin-like growth factors has neoplastic effects in the
presence of high estrogen levels stimulating endometrial prolferation and neoplastic
changes; (2) insulin resistance results in decrease in circulating sex hormone binding
globulins, which increases circulating free estrogen

III. PREVENTION
PRIMARY PREVENTION
• Inclusion of progesterone in hormone replacement therapy
• Use of oral contraceptive pills
• Use of Raloxifene (instead of Tamoxifen)
• Behavior modification: weight reduction and maintenance, balanced diet, regular
physical activity with appropriate intensity level; regular gynecologic check-up and
prompt consultation upon onset of symptoms
 SECONDARY PREVENTION
1. For low risk patients, there is no routine screening warranted.
2. For moderate risk patients – those with unopposed estrogen therapy, late
menopause, Tamoxifen therapy, nulliparity, infertility, chronic anovulation, obesity
and diabetes mellitus – no routine screening is warranted.
3. For high risk patients – those who carry HNPCC associated mutations, those who have
a substantial likelihood of being a mutation carrier, or those whose families carry an
autosomal dominant predisposition to colon cancer – annual screening with
endometrial biopsy should be offered by age 35.
4. There is no role for routine screening with endometrial biopsy of transvaginal
ultrasound in asymptomatic women on Tamoxifen.

The general criteria for a screening test are that it should have a high predictive
value and be easily applied to a large group of women, be inexpensive, and able to
diagnose disease ideally in a premalignant phase. Unfortunately, there is no
satisfactory screening test that satisfies these criteria for endometrial carcinoma
(pap smear, ultrasound, endometrial biopsy). Routine screening of women for
endometrial cancer is not of any proven benefit.
A variety of simple, easily used instruments are available for obtaining office
endometrial samples, but neither of these devices nor ultrasonography screening
meet the criteria for an effective screening test for this disease. Similarly, cervical
cytology will be abnormal in less than half of endometrial carcinoma patients.
Transvaginal ultrasound is often used to determine endometrial thickness with a
value of 4 mm as a ‘cut-off’, the level for normal thickness in postmenopausal
women.

IV. CLINICAL PRESENTATION

• Perimenopausal and postmenopausal bleeding
Most common symptom (Hoskins): vaginal discharge
• Symptomatic women who are at high risk for the disease:
• Any postmenopausal woman with bleeding or perimenopausal woman with heavy
and/or irregular vaginal bleeding; or abnormal vaginal discharge
• Postmenopausal women with endometrial cells seen on pap smear or
premenopausal women with atypical glandular cells on pap smear
• Breast cancer patients on Tamoxifen who complain of abnormal vaginal bleeding
• Women who are still “menstruating” after 52 years of age (may not do sampling
but should monitor closely)
• Women in reproductive age group who have menorrhagia/menometrorrhagia
• The physician should have a high index of suspicion especially in a woman who has
defined risks for endometrial carcinoma. Vaginal bleeding should not be regarded as
a normal perimenopause or menopausal symptom until a thorough proper evaluation
has been done and an organic pathology has been ruled out.
• Any woman in her 20's with anovulatory cycles who suddenly presents with
menometrorrhagia and has strong risk factors for endometrial cancer, any woman
with abnormal perimenopausal bleeding should have proper diagnostic evaluation.
• Pelvic pain, enlarged corpus, urinary/bowel symptoms – late signs

V. DIAGNOSIS
• Histologic verification of endometrial tissue is required to make the diagnosis of
endometrial carcinoma
• Presently, office endometrial biopsy is recommended as the first step in evaluating
women with postmenopausal bleeding or suspected endometrial pathology.
Endometrial biopsy has an accuracy of 90%. The uterine cavity is sampled afterwards
with the curette using the Z-technique.
• Endocervical curettage is NO LONGER NECESSARY IN DIAGNOSIS.
• Indications for endometrial curettage:
• Cervical stenosis
• Distorted pelvic anatomy because of associated pelvic pathology (e.g. fibroids)
• Patient intolerance to pain
• Endometrial biopsy yields insufficient tissue sample that precludes adequate
histologic diagnosis in a woman where endometrial pathology is highly suspected
• In patients who continue to bleed in spite of insignificant results of previous
endometrial biopsy
• Patients who have been diagnosed with endometrial hyperplasia with or without
atypia.
• Hysteroscopy is employed only when the endometrial biopsy and/or the endometrial
curettage has negative results. Although there is a theoretical risk of transporting
malignant cells into the peritoneal cavity during the procedure, there has been no
clear evidence that this worsens the prognosis.
• Transvaginal ultrasound has been proposed to screen postmenopausal women with
abnormal uterine bleeding before performing curettage with an upper limit of 4 mm
endometrial thickness. Hence, sonography can be used to triage patients for
endometrial sampling. Endometrial fluid in the absence of a thickened stripe may not
be a significant finding in asymptomatic women. Individuals whose pelvic
examination is unsatisfactory may also be evaluated with transvaginal or abdominal
ultrasound to rule out concomitant adnexal pathology.

In a study done by Dr. F Santiago-San Juan, UTZ accuracy in predicting:

• Myometrial invasion
Sensitivity = 77%
Specificity = 82%
Positive predictive value = 81%
Negative predictive value = 78%

• Cervical involvement
Sensitivity & positive predictive value = 86%
Specificity & negative predictive value = 96%

• With 5 mm cut off

Positive predictive value = 87%
Sensitivity = 96%
Specificity = 100%

• In over 80% of patients there is no clinical evidence of extrauterine disease, and for
such patients the only additional studies required are chest X-ray and the usual
preoperative chemistries. A serum CA-125 may also be of value in following advanced
disease. The use of CT scan, barium enema or MRI in the preoperative evaluation of
such patients may be indicated in those individuals whose disease has features
suggesting that they are at high risk for metastasis.
• Evaluation for metastasis is indicated in patients with abnormal liver function tests,
an elevated serum CA-125 value, and clinical findings of metastasis, such as
parametrial or vaginal tumor extension. In certain situations, cystoscopy and/or
barium enema may be helpful as well as bone and brain scan in patients with specific
symptoms suggesting involvement of these organs.
• The role of DNA ploidy, tumor size, and molecular or biological markers in treatment
planning has not been established. Similarly, estrogen and progesterone receptor
status, although advocated by some investigators, has not been proved to be of value
in planning therapy.
VI. BASIC WORKING KNOWLEDGE
A. General Guidelines
1. Once a diagnosis of endometrial carcinoma has been made by endometrial biopsy or
endometrial curettage, the next most important step is to determine the extent of
the disease as expressed by its stage.
2. In 1988, FIGO changed the staging for endometrial cancer from a clinical to a surgical
staging system. Even with the clinical staging system it was always appreciated that
histopathologic and/or surgical findings determined the need for adjunctive
therapies. Clinical staging, however, still remains important in terms of preoperative
assessment and planning for subsequent surgery and correlates well with prognosis.
Clinical staging for endometrial cancer is generally thought to have an inherent
inaccuracy rate in the order of 19%. Node metastases, degree of myometrial invasion,
intraperitoneal implants and adnexal metastasis, as well as lymphatic-vascular space
(LVS) involvement are not readily evaluated clinically. Approximately 20% of tumors
may have a worse histologic grade based on the hysterectomy specimen compared to
the curettage.
3. All patients should undergo the 2009 FIGO surgical staging after appropriate
investigation and clearance.
Exceptions:
• 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.
• 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.
• Patients with a well-differentiated lesion and contraindications to general
anesthesia and unsuited for radiotherapy, high-dose progestins may be used.10
4. All specimens should be cut and examined immediately after removal to determine
the further extent of surgery.

B. FIGO surgical staging for endometrial cancer

1971 FIGO STAGING

Stage I Tumor confined to the corpus uteri

Stage IA Uterine depth of < 8 cm
Stage IB Uterine depth of > 8 cm
Stage II Tumor invades cervix but does not extend beyond uterus
Stage III Tumor extends outside the uterus but not outside the pelvis
Stage IV Tumor extends outside the pelvis or involves the bladder or rectum

2009 FIGO STAGING

Stage I Tumor confined to the corpus uteri

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

C. Architectural grading/degree of differentiation of endometrial carcinoma:

Cases of carcinoma of the corpus should be grouped with regard to the degree of
differentiation of the adenocarcinoma as follows:
G1: 5% of a non-squamous or non-morular solid growth pattern
G2: 6-50% of a non-squamous or non-morular solid growth pattern
G3: > 50% of a non-squamous or non-morular solid growth pattern

Nuclear grading/degree of differentiation of endometrial carcinoma:

G1: round to oval nuclei; even distribution of chromatin; inconspicuous nucleoli
G2: irregular, oval nuclei; chromatin clumping; moderate sized nucleoli
G3: large, pleomorphic nuclei; coarse chromatin; large irregular nucleoli

D. Pathologic classification (WHO/ISGP – International Society of Gynecologic

Pathologists Classificaton)
Endometrioid adenocarcinoma
Villoglandular
Secretory
Ciliated cell
Endometrioid adenoCA with squamous differentiation
Serous carcinoma
Clear cell carcinoma
Mucinous carcinoma
Squamous carcinoma
Mixed types of carcinoma
Undifferentiated carcinoma

E. HISTOPATHOGENIC TYPES OF ENDOMETRIAL CARCINOMA

Clinical Features Type I Type II

Age Pre- and postmenopausal Post-menopausal
Body type/habitus Obese Thin
Hyperlipidemia + -
Parity Nulliparous Multiparous
Unopposed estrogen/ + -
hyperestrogenism
(anovulatory uterine
bleeding, infertility, late
onset menopause)
Hyperplasia precursor + -
Race White > Black White = Black
Histologic grade Well- to moderately Poorly differentiated
differentiated
Myometrial invasion Minimal or superficial Deep
Histologic type Endometrioid Poor histologic type
(papillary serous, clear cell)
Stage Early stage: I/II Advanced stage: III/IV
Prognosis Favorable Unfavorable
VII. MANAGEMENT OF ENDOMETRIAL CANCER
A. GENERAL GUIDELINES
1. Endometrial cancer follows a surgico-pathologic staging.
2. Primary surgical approach in the form of extrafascial hysterectomy, BSO, PFC, and
lymph node evaluation is done.
3. In selected cases, where there is histopathologic evidence of tumor extension to the
cervix, primary radical hysterectomy, BSO, PFC and lymph node evaluation may be
performed by a gynecologic oncologist.
4. Adjuvant treatment in the form of radiotherapy and chemotherapy is given
depending on the stage of the disease, and presence of surgico-pathologic prognostic
factors. Current evidence does not support the use of adjuvant progestagen therapy
in the primary treatment of endometrial cancer.
5. The treatment of endometrial cancer requires a multidisciplinary approach involving
a gynecologic oncologist and a radiation oncologist.

B. Surgical staging procedure for endometrial cancer

1. A generally recommended approach for the surgical staging of endometrial cancer
would be that the abdomen should be opened with a vertical midline abdominal
incision and peritoneal washings taken immediately of the pelvis and abdomen,
followed by a careful exploration of the intra-abdominal contents.
2. The omentum, liver, peritoneal cul-de-sac and adnexal surfaces should be examined
and palpated for any possible metastases, followed by careful palpation for
suspicious or enlarged nodes in the aortic and pelvic nodal areas.
3. The standard surgical procedure should be an extrafascial hysterectomy with
bilateral salpingo-oophorectomy.
4. Ligation or clipping of the distal tubes should be performed initially to prevent any
possible tumor spillage during manipulation of the uterus and adnexa.
5. Adnexal removal is also recommended even if the adnexa appear normal. Primary
reason for this procedure is that there is an increased association with a primary
ovarian CA; secondary reason is probability of micrometastasis.
6. A vaginal rim and parametria is also removed during the procedure.
7. Entire cervix should be removed and, if cervical involvement is noted and can be
encompassed by a radical hysterectomy, then this may be the most appropriate
action in experienced hands.
8. Latest SGOP guideline recommends adequate lymphadenectomy. Lymph node
palpation is not acceptable. Decision to omit lymphadenectomy should be made
together with a gynecologic oncologist.
9. Many individuals with endometrial cancer are obese or elderly, with other medical
problems, and clinical judgment is required to determine if additional surgery is
warranted.
10. Once the uterus has been removed, it should be opened outside the operative field to
determine the extent of the growth. If the depth of invasion is not grossly evident,
frozen section, if available, may be helpful to make this assessment.
11. Indications for para-aortic node sampling would include
• Suspicious aortic or common iliac nodes
• Grossly positive adnexa
• Grossly positive pelvic nodes
• Any grade of tumor showing full thickness myometrial invasion
• Patients with clear cell, papillary serous or carcinosarcoma histologic subtypes
• Cervical involvement
• Lower uterine segment involvement
12.There have been two basic approaches regarding the initial management of
endometrial carcinoma.
• The standard approach is to do primary surgery. Findings at staging laparotomy
and the histopathologic evaluation are then used to determine the final stage and
 need for additional adjunctive therapy. This is the preferred/recommended
therapeutic option.
• For patients with contraindictations for primary surgery or with far advanced
stage, preoperative irradiation followed by surgery may be done. With
preoperative irradiation, external irradiation followed by intracavitary
brachytherapy is used prior to surgical removal.

ENDOMETRIAL CARCINOMA: CLINICAL PRACTICE GUIDELINE SUMMARY

(based on 1988 FIGO staging)

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)

* Lymph Node Evaluation: 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.
** Lymph node palpation has a sensitivity of only 72%.

Notes:
1. Adjuvant treatment for adenocarcinoma with squamous differentiation will depend on
the histologic grade of the glandular component.
2. If there is lymphovascular space invasion (LVSI), SGOP recommends adjuvant therapy.
Options are pelvic EBRT OR chemotherapy (Paclitaxel or Doxorubicin containing
regimen).
3. For uterine papillary serous carcinoma (UPSC) and clear cell types, extended surgical
staging, which involves infracolic omentectomy and random peritoneal biopsy has to be
done.
4. The major disadvantage of preoperative irradiation is that some patients will have less
disease than originally thought, thus receiving irradiation that is not necessary.
5. Preoperative irradiation is thought to lessen the likelihood of vaginal vault recurrence
post-treatment or the likelihood of tumor spread at the time of surgery. Data from
subsequent studies have not supported this approach.
• Individuals with disease outside of the radiated field, i.e. suspected metastases,
particularly in the paraaortic chain or within the abdominal cavity were inadequately
treated with this approach.
6. Decision to use adjuvant radiotherapy depends on surgical pathologic risk factors such as
FIGO stage
Tumor grade
Histologic type
Depth of myometrial invasion
Adnexal involvement
Cervical involvement
Isthmic involvement
Lymphovascular space invasion
Nodal status
 Intraperitoneal spread
Peritoneal fluid cytology status
7. In any other scenario that confers a higher risk warrants consideration for adjuvant
postoperative pelvic irradiation.
8. If metastases to the aortic nodes are documented, extended field radiotherapy is also
recommended in the absence of widespread disease.
9. Vaginal cuff radiotherapy is not routinely administered in conjunction with postoperative
external beam radiotherapy. Radiotherapy offers local or regional disease control. In the
vast majority of endometrial cancer treatment failures and death results from disease
outside of the radiation field. Local recurrences can be cured with appropriate
radiotherapy. Thus the role of adjuvant radiotherapy in prolonging overall survival in
endometrial cancer is not well defined.
10. Laparoscopically-assisted vaginal hysterectomy and laparoscopic lymphadenectomy is a
procedure that is appropriate.
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.
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.

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 Observe33 (Level 2b)
evaluation

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
G1, G2, G3 brachytherapy followed by PFC & EHBSO
with selective lymphadenectomy (common
iliac and para-aortic)10,36 (Level 4)
Notes:
1. If there is lymphovascular invasion (LVSI), SGOP recommends adjuvant therapy. Options
are pelvic EBRT OR chemotherapy (Paclitaxel containing regimen).
3. For clinical Stage II uterine papillary serous carcinoma (UPSC) and clear cell types,
recommended primary surgery is EHBSO, PFC, lymph node evaluation and extended
surgical staging which involves infracolic omentectomy and random peritoneal cytology
followed by adjuvant therapy (chemotherapy and abdominopelvic radiotherapy).

STAGE III: Tumor extension outside the uterus, within the pelvis
SURGERY: EHBSO, PFC, Lymph Node Evaluation, Debulking
ADJUVANT CHEMOTHERAPY 37 (Level 1A) followed by
ADJUVANT RADIATION38 (Level 2b)
SURGICO-PATHOLOGIC STAGING ADJUVANT TREATMENT*
IIIA (+) PFC with no other No adjuvant treatment39 (Level 2b)
poor prognostic factors
IIIA, (+) PFC, with other Chemotherapy (recurrence patterns*
poor prognostic factors suggest that systemic therapies are
appropriate)40
Followed by Pelvic EBRT
IIIA (+) uterine G1,G2, G3 Chemotherapy followed by Pelvic EBRT
serosa/adnexal metastasis
IIIB G1,G2, G3 Chemotherapy followed by Pelvic EBRT
+ vaginal brachytherapy
IIIC G1,G2, G3 Chemotherapy followed by EFRT** +
vaginal brachytherapy

Notes:
1. If an individual is in a clinical Stage III category, because of adnexal mass or
involvement, as noted on ultrasound, these individuals should undergo surgery without
preoperative radiotherapy, to determine the nature of the mass and to perform surgical
pathological staging. In many instances cytoreductive surgery can be carried out and if
the uterus is resectable then hysterectomy and adnexectomy should be performed.
2. In some instances, rather than metastases to the ovary, one may find that the patient
has a primary lesion of both the endometrium and also of the ovary after histologic
examination of the removed tissue.
3. The best choice of chemotherapeutic agents is a combination of:
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 Regimen 44 (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 50 mg/m2 concurrent with EBRT 4500 cGy followed by vaginal
brachytherapy then Cisplatin 50 mg/m2 - Paclitaxel 175 mg/m2 every 4 weeks for 4
courses
 e. Carboplatin (AUC=5) with pegylated liposomal doxorubicin (40 mg/m2) every 4 weeks
for 6 cyles46 (Level 2b) (Phase II study)
4. Hormonal therapy is currently not recommended as primary treatment for endometrial
cancer.

STAGE IV: Tumor invades bladder and/or bowel mucosa, +/- distant metastasis
SURGERY: EHBSO, Debulking
ADJUVANT CHEMOTHERAPY 37 (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)

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.
3. Patients with evidence of extrapelvic metastases are usually managed with systemic
chemotherapy followed by radiotherapy (EFRT + vaginal brachytherapy).
4. Local irradiation may be beneficial, particularly in brain or bone metastases and
occasionally pelvic radiotherapy may help in providing local tumor control and prevent
bleeding or complications from local disease.
5. The value of whole abdominal radiotherapy for endometrial cancer, involving the
parametrial cavity, is uncertain. It would appear to be most applicable in cases that have
no macroscopic abdominal disease and no distant metastases.

VIII. Special considerations

A. Diagnosis post-hysterectomy
• Diagnosis of endometrial carcinoma post-hysterectomy can present some difficult
management problems, particularly if the adnexa had not been removed. In this
situation, which most often arises following vaginal hysterectomy for pelvic
relaxation, the problem can often be avoided by opening the excised uterus routinely
in the operating room with subsequent pathologic assessment if suspicious findings
are noted.
• Recommendations for further postoperative therapy are based on known risk factors
for extrauterine disease related to the histologic grade and depth of myometrial
involvement

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

no LVSI perform surgical staging and give

< 2 cm28 adjuvant treatment 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

(+) LVSI55 perform surgical staging and give adjuvant

(+) evidence of metastasis treatment accordingly

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
involvement (Stage IIIA) Pelvic EBRT
Positive LVSI55 G1, G2, G3 Re-operate for
lymphadenectomy
• If lymph node is (+), for
chemotherapy followed by
EFRT
• If lymph node is (-), for
pelvic EBRT
OR
Give adjuvant therapy

B. Medically inoperable patient

• Morbid obesity and severe cardiopulmonary disease are the general reasons a patient
with endometrial carcinoma is usually thought to be medically inoperable.
• For patients with a grade 1 lesion and contraindications to general anesthesia and for
those who are unsuited for radiotherapy entirely, high dose progestins are the
treatment of choice.
• All of the patients should be treated with radiotherapy with or without
chemotherapy.

C. Diagnosis in the young woman

• The diagnosis of endometrial carcinoma during the reproductive years should be
made with caution, since this malignancy is uncommon and may be confused with
hyperplasia in these situations.
• Atypical hyperplasia and well differentiated, stage 1A endometrial cancer have been
treated successfully with progestins, and the decision to use progestins in these
situations is to be carefully weighed but may be appropriate if preservation of
fertility is the highly desirable clinical factor.
• Any equivocal lesion, once an experienced pathologist has carefully examined the
specimens, can be managed in a similar fashion to atypical hyperplasia. If carcinoma
is confirmed, hysterectomy with adnexal removal remains the treatment of choice.
• Nonetheless, the ultimate decision rests with the patient and the patient should
undergo thorough counseling and documentation if a conservative approach is
followed.
If conservative treatment is contemplated, pre-treatment evaluation must be
employed
• History and physical exam
Comprehensive physical & gynecologic exam
Fertility history of both patient and spouse
Family history
• 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)
• Pathology review
• Imaging with contrast-enhanced MRI60 (Level 1a)
MRI provided the highest diagnostic accuracy for determining myometrial
invasion at 85-91 %.
Studies using ultrasound with Doppler have conflicting results regarding
determination of myometrial invasion.61,62,63,64,65 (Level 2b)
In smaller scale studies, FDG PET scan has also shown usefulness in
predicting myometrial invasion in endometrial cancer.66 (Level 2b)
• Tumor marker: CA-125
• 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
• Molecular markers (progestin receptors)

Conservative treatment is only offered to patients who have:

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

The following are also essential:

• Progestin receptor positivity
• Careful, thorough, informed consent – Inform patients that the procedure of
preservation of fertility is still experimental and there is low pregnancy rate.
• Patient with strong desire to preserve her childbearing potential

Agents used:
• Megestrol acetate 40 -160 mg/day Duration of treatment is
• Medroxyprogesterone acetate 100 – 800 mg/day
variable.
Other agents used:
• Tamoxifen + progestins
• Anastrozole + progestins
• Levonorgestrel-containing IUS

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.

D. Positive peritoneal cytology

• The presence of positive peritoneal cytology, which is often a difficult diagnosis,
given the malignant appearance of reactive mesothelial cells, should only be made
after a thorough cytopathology review.
• Positive peritoneal cytology has an adverse outcome on survival only if the
endometrial cancer had spread to the adnexa, peritoneum or lymph nodes but not if
disease confined to the uterus.
• In the absence of other poor prognostic factors, no additional therapy is needed with
a positive peritoneal fluid.
• In 2009 FIGO staging, positive peritoneal fluid cytology is no longer part of the
staging but is reported separately

E. Recurrence
• Localized recurrences are managed preferentially by surgery, irradiation, or
chemotherapy. Large lesions, should be excised, if feasible, with isolated pelvic
recurrence of any grade being potentially curable if it occurs more than 1 or 2 years
after initial therapy.
• Patients with nonlocalized recurrent tumors may be candidates for progestin therapy
medroxyprogesterone acetate 50-100 mg TID or megestrol acetate 80 mg two to
three times per day.
• The progestin therapy is continued as long as the disease is static or in remission.
Maximum clinical response may not be apparent for 3 or more months after initiating
therapy.
• 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/m 2 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)

HORMONAL REPLACEMENT THERAPY FOR ENDOMETRIAL CANCER

The prevailing belief that HRT in these patients somehow accelerates disease recurrence is not
supported in the current literature, and until results are available from Gynecologic Oncology
Group protocol # 137, it should not be endorsed. To this end, the American College of Obstetrics
and Gynecology has issued a committee opinion stating " in women with a history of endometrial
carcinoma, estrogens could be used for the same indications as for other women, except that
the selection of appropriate candidates should be based on prognostic indicators and the risk
the patient is willing to assume."

Hormonal replacement therapy may be given to endometrial cancer patients depending on the
clinician's discretion based on the following:
• the patient has good prognostic factors
• the patient has no evidence of disease for 5 years
• estrogen replacement be given with progesterone
 • non-estrogenic treatment should be extensively utilized

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)
UTERINE SARCOMAS

Classification (WHO & ISGYP [International Society of Gynecologic Pathologists])

Leiomyosarcoma
Endometrial Stromal Sarcoma (low grade or high grade)
Malignant Mixed Mullerian Tumors (homologous or heterologous)
Unclassified

2009 FIGO Surgical staging for Leiomyosarcoma

STAGE I Tumor limited to the uterus

IA < 5 cms
IB > 5 cms
STAGE II Tumor extends to the pelvis
IIA Adnexal involvement
IIB Tumor extends to extrauterine pelvic tissue
STAGE III Tumor invades abdominal tissues (not just
protruding into the abdomen)
IIIA One site
IIIB > one site
IIIC Metastasis to pelvic and/or para aortic lymph
nodes
STAGE IV Metastasis to bladder or rectum and distant
metastasis
IVA Tumor invades bladder and/or rectum
IVB Distant metastasis

2009 FIGO Surgical staging for Endometrial Stromal Sarcoma

STAGE I Tumor limited to the uterus

IA Limited to the endometrium/endocervix with
no myometrial invasion
IB Less than or equal to half myometrial invasion
IC More than half myometrial invasion
STAGE II Tumor extends to the pelvis
IIA Adnexal involvement
IIB Tumor extends to extrauterine pelvic tissue
STAGE III Tumor invades abdominal tissues (not just
protruding into the abdomen)
IIIA One site
IIIB > one site
IIIC Metastasis to pelvic and /or para aortic lymph
nodes
STAGE IV Metastasis to bladder and/or rectum and
distant metastasis
IVA Tumor invades bladder and/or rectum
IVB Distant metastasis

* Staging for carcinosarcoma follows that of endometrial cancers

1. MALIGNANT MIXED MULLERIAN TUMOR

STAGE Primary Treatment Adjuvant Treatment

I and II EHBSO, PFC, Pelvic RT to include upper half of
Lymphadenectomy, IO, the vagina4 (Level 1b)
peritoneal biopsy2,3 OR
(Review Article, Level Cisplatin 20 mg/m2 (over 15 mins) -
2b) 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) +
Lymphadenectomy, IO, Paclitaxel 135 mg/m2 (3 hour
peritoneal biopsy2,3 infusion on day 1) + Filgrastim
(Review Article, Level support7 (Level 2b)
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-Doxorubicin 10 (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

2. LEIOMYOSARCOMA

STAGE Primary Treatment Adjuvant Treatment

I and II EH Doxorubicin 60 mg/m2 every 3 weeks
(BSO*, LND not (maximum of 480 mg/m2)14 (Level
mandatory)2,12,13 (Review 1b) - results favor only LMS but no
Articles, Level 2b) difference in PFS and survival

With 15,16 (Level 2b) or without4 (Level

1a) subsequent Pelvic EBRT and
vaginal brachytherapy
III and IV EH Doxorubicin 60mg/m2 to a maximum
(BSO*, LND not of 480 mg/m17,18 (Level 1b, Level 2b)
mandatory)2,12,13 (Review OR
Articles, Level 2b) Ifosfamide plus Doxorubicin19 (Level
2b)

PERSISTENT/RECURRENT DISEASE

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)

3. ENDOMETRIAL STROMAL SARCOMA

STAGE Primary Treatment Adjuvant Treatment

I and II EHBSO, PFC, Pelvic/Peri- Pelvic EBRT16,22 (Level 2b)
aortic LN Dissection/
Assessment 2,12 (Review If high-grade, chemotherapy with:
Article, Level 2b) 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- Ifosfamide 1.5 g/m2 x 5 days every 3
aortic LN Dissection/ weeks for 6-8 courses plus Mesna24
Assessment2,12 (Review (Level 2b)
Article, Level 2b)
Followed by pelvic EBRT16,22 (Level
2b)

PERSISTENT/RECURRENT DISEASE
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.
OVARIAN CANCER

I. INCIDENCE
• Peak incidence: 50-59 years old (63 years old)
• Certain types occur in the young
• Age range 16-72 years (peak age: 8th decade)
• Age standardized rate 12.5/100T females

II. RISK FACTORS

BRCA 1 mutation 40%

BRCA 2 mutation 10-20%
HNPCC associated risk 5-10%
Early menarche < 12 years
Late menopause
Unopposed estrogen / HRT 1.89-3.09x
Endometriosis 3x
Polycystic ovarian syndrome 2.5x
Pelvic inflammatory disease
Obesity 1.3x
Cigarette smoking 2.1x
High meat, high fat diet 2.49x
Nulliparity 2.5%
White race 1.86%
General population 1.6% (1.82%)

III. PRIMARY PREVENTION

1. Reduction of incessant ovulation
• Use of oral contraceptive pills
• Pregnancy / increasing parity
• Breastfeeding
2. Prophylactic bilateral oophorectomy (of limited benefit because of the risk of
primary peritoneal carcinoma)
• At hysterectomy for benign disease at age 45 years or above
• For BRCA1 carriers: at 35-40 years old; for BRCA2 carriers: at 45 years
3. Tubal ligation, hysterectomy
4. NSAIDs, acetaminophen
5. Carotenoids
6. Tea consumption
7. Physical activity

IV. SECONDARY PREVENTION

1. There is no cost-effective screening method for ovarian cancer.
2. Patients with high risk factors may benefit semi-annual examinations
• Careful bimanual and rectovaginal examination
• Transvaginal ultrasonography
• CA 125 determination
* Screening for high risk patients should start at 35 years old
** The results of the 3 examinations should be taken collectively.
3. Additional genetic testing for BRCA 1 or 2 mutation should be done for those with
familial cancer syndromes
V. CLINICAL PRESENTATION
1. Early Stage:
• Asymptomatic
• Nonspecific gastrointestinal symptoms (i.e. bloating, flatulence)
2. Late Stage:
• Pelvic mass – irregular and fixed
• Abdominal distension
• Abdominal pressure – urinary frequency, constipation
• Abdominal pain
• Ascites
• Bloating
• Nausea
• Anorexia
• Abnormal vaginal bleeding
• Irregular menses (if premenopausal)

PREOPERATIVE EVALUATION
1. Basic
• Complete physical examination to include pelvic and rectovaginal examination*
• Chest x-ray
2. Optional
• Transvaginal ultrasound – spec 97.5% PPV 25%, if with color doppler 99.9%, 60%
• Barium enema, UGIS, proctosigmoidoscopy, KUB-IVP
• Tumor markers – CA 125, HE4
• CT scan - 50% of peritoneal implants > 5 mm (sens 63%, spec 100%, PPV 100%, NPV
52%)
• MRI/PET scan
• Abdominal ultrasound that includes the liver
*PE findings that suggest malignancy: ascites, irregular solid tumors, large tumors

VII.TREATMENT

1. Guidelines for Complete Surgical Staging

• A vertical incision that allows adequate evaluation of the entire abdomen
• Collection of peritoneal fluid/washing for cytology (4 areas: subdiaphragmatic area, 2
hemi-abdomen, pelvis)
• Comprehensive/systematic abdominal exploration
• Careful inspection and palpation of all peritoneal surfaces
• Biopsy and resection of suspicious lesions, masses and adhesions
• Intact tumor removal
• Total hysterectomy with bilateral salpingooophorectomy (conservative surgery only
when indicated)
• USO is permitted in young women with stage IA-IB, grade 1-2 disease wanting to
retain their fertility
• Infracolic omentectomy (total or infragastic omentectomy is done if there is gross
involvement of the omentum)
• Pelvic and para-aortic lymph node evaluation*
• Random biopsies (2 each) of bladder peritoneum, cul-de-sac, right and left paracolic
gutter, hemidiaphragm and pelvic side wall peritoneum at the side of the primary
tumor (ovarian fossa)
* Lymph node palpation, sampling lymphadenectomy, systematic lymphadenectomy, fine
needle aspiration biopsy
 2. Guidelines for referral to a gynecologic oncologist
• Pre-operative consult with gynecologic oncologist is recommended if malignancy is
clinically suspected
• Intra-operative referral warranted if:
• The lesion is grossly suggestive of malignancy:
Solid tumors, ascites, tumor implants in other areas, papillary excrescences, thick
septae, solid areas, large tumors
• Frozen section reveals malignant tumor

3. Rationale for above recommendation:

Adjusted survival was improved if the initial surgery was done by a gynecologic
oncologist (RR 0.70, 95% CI 0.57-0.85) and survival benefit in the order of 25% at 3 years
Surgery by a gynecologic oncologist resulted in longer survival in subgroups of patients,
leading to a 5- to 8-month median survival benefit for patients with advanced stage
disease.

4. Frozen Section
• Pre-requisite to conservative surgery
• Ideal prior to pelvic and para-aortic lymph node dissection

5. Pregnant patients with ovarian malignancy

a. Conservative surgery (USO, IO, PFC, complete surgical staging) is standard for early
stage.
b. Conservative surgery, followed by antepartal chemotherapy (Cisplatis-
Cyclophosphamide) for advanced disease beyond second trimester
c. Completion surgery postpartum for advanced diseases or for early stages not desirous
of pregnancy

VIII. BASIC WORKING KNOWLEDGE

A. FIGO Staging

Stage I Growth limited to the ovaries

A. One ovary; no ascites; capsule intact; no tumor on external surface
B. Two ovaries; no ascites; capsule intact; no tumor on external surface
C. One or both ovaries with ruptured capsule, surface tumor, positive ascites, or positive
peritoneal washings
Stage II Pelvic extension
A. Involvement of uterus or fallopian tubes
B. Involvement of other pelvic tissues
C. Stage IIA or IIB with ruptured capsule, surface tumor, positive ascites, or positive
peritoneal washings
Stage III Peritoneal implants outside the pelvis or positive retroperitoneal or inguinal lymph
nodes
A. Grossly limited to the true pelvis with microscopic seeding of abdominal peritoneum
B. Implants on abdominal peritoneum not exceeding 2 cm in diameter
C. Implants on abdominal peritoneum exceeding 2 cm in diameter or positive retroperitoneal
or inguinal lymph nodes
Stage IV Distant metastases; parenchymal liver metastases
B. WHO Classification of Ovarian Tumors

Epithelial Tumors
• Serous tumors
• serous cystadenomas
• serous cystadenomas of borderline malignant potential
• serous cystadenocarcinomas

• Mucinous tumors
• mucinous cystadenomas
• mucinous cystadenomas of borderline malignant potential
• mucinous cystadenocarcinomas

• Endometrioid tumors
• endometrioid cystadenomas
• endometrioid cystadenomas of borderline malignant potential
• endometrioid cystadenocarcinomas
• Clear cell tumors
• Clear cell cystadenomas
• Clear cell cystadenomas of borderline malignant potential
• Clear cell cystadenocarcinomas

• Brenner
• Benign Brenner
• Borderline malignancy
• Malignant
• Transitional cell

• Undifferentiated carcinomas
• Mixed epithelial tumors

Germ Cell Tumors

• Dysgerminoma
• Endomermal sinus tumor / Yolk sac tumor
• Embryonal carcinoma
• Polyembryoma
• Choriocarcinoma
• Teratomas
• Immature
• Mature
• solid
• cystic
• dermoid cyst
• dermoid cyst with malignant transformation
• Monodermal and highly specialized
• struma ovarii
• carcinoid
• struma ovarii and carcinoid
• others
• Mixed forms

Sex Cord Tumors

• Granulosa-stromal tumors
• Granulosa cell tumor
• Tumor in the thecoma-fibroma group
• thecoma
 • fibroma
• unclassified
• Androblastomas; sertoli-leydig cell tumors
• well differentiated
• tubular androblastoma; sertoli cell tumor
• tubular androblastoma with lipid storage; sertoli cell tumor with lipid storage
• sertoli-leydig cell tumor
• leydig cell tumor; hilus cell tumor
• intermediate differentiation
• poorly differentiated (sarcomatoid)
• with heterologous elements
• Gynandroblastoma
• Unclassified

IX. MANAGEMENT OF OVARIAN CANCER

GENERAL GUIDELINES
1. Ovarian cancer follows surgico-pathologic staging.
2. There should be histologic confirmation of the disease.
3. Clinical and imaging studies and tumor markers may be helpful in both initial staging
and follow-up of tumors.
4. Pleural effusion should be aspirated for cytology. For patients with pleural effusion
with negative cytology and no evidence of pulmonary metastasis on x-ray, chest CT
scan is recommended.
5. Frozen section for young patients desirous of pregnancy.
6. For epithelial ovarian tumors of low malignant potential, USO/THBSO, IO, PFC,
complete surgical staging (LN assessment, random peritoneal biopsy) is done.
Adjuvant treatment in advanced stages is in the form of platinum based
chemotherapy.
7. For frankly malignant epithelial ovarian tumors, primary cytoreductive surgery is
done. USO/THBSO, IO, PFC, complete surgical staging (LN assessment, random
peritoneal biopsy) is performed. Adjuvant treatment in advanced stages is in the
form of platinum based chemotherapy.
8. For Sex Cord/Stromal tumors, USO/THBSO, IO, PFC, complete surgical staging (LN
assessment, random peritoneal biopsy) is done. Adjuvant treatment is chemotherapy
with BEP/VAC/CAP/Carboplatin-Paclitaxel.
9. For germ cell tumors, USO/THBSO, IO, PFC, complete surgical staging (LN
assessment, random peritoneal biopsy). Conservative management can be done in all
stages if patient is desirous of pregnancy. Adjuvant treatment is chemotherapy with
BEP/PVB/VAC/CAP/Ifosfamide-Doxorubicin/Vinblastine-Ifosfamide-Cisplatin.

SGOP TREATMENT GUIDELINES

I. EPITHELIAL OVARIAN TUMORS, LMP

STAGE STATUS INTERVENTION4,5 (Level 2b) ADJUVANT

THERAPY
Young/desirous of USO/BSO, IO, PFC, complete surgical
None*
pregnancy staging
IA - IB
Reproductive function not THBSO, IO, PFC, complete surgical
None*
desired staging
Optimally debulked
(residual tumor < 2.0 cm) or Chemotherapy
IC - IV THBSO, IO, PFC ± tumor debulking
Sub-optimally debulked (Consensus-based)
(residual tumor ≥ 2.0cm)
 *
Adequate sections (at least 1 section per cm of the greatest diameter of the tumor) should be
taken to make sure that a focus of invasive carcinoma was not missed on histopathologic
examination; otherwise, chemotherapy should be considered.

Special Clinical Situations

Do diagnostic imaging (CT Scan / MRI)

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

II. FRANKLY MALIGNANT EPITHELIAL OVARIAN TUMORS

Risk groups of patients with limited ovarian carcinoma

Low risk group Grade 1 disease
Intact capsule
No tumor on external surface
Negative peritoneal cytology
No ascites
Growth confined to ovaries

High risk group Grade 2-3 disease

Ruptured capsule
Tumor on external surface
Positive peritoneal cytology
Ascites
Growth outside ovaries
Poor histologic type-clear cell, papillary serous

STAGE STATUS INTERVENTION ADJUVANT THERAPY

IA – USO, IO, PFC, complete surgical
IA - IB
staging
(G1, Young/desirous of pregnancy
IB – BSO, IO, PFC, complete surgical
G2) None 7, 8 ,9 (Level 1a)
staging
Reproductive function not
THBSO, IO, PFC, complete staging
desired
THBSO, IO, PFC, Complete surgical
IA – IB Optimally debulked Chemotherapy*
staging
(G3),
THBSO, IO, PFC, Complete surgical Chemotherapy*
IC - III Sub-optimally debulked
staging followed by IDS**
Optimally or Sub-optimally Chemotherapy* 10
IV THBSO, IO, Tumor Debulking
debulked (Level 2b)

Dosage:
• Paclitaxel (175mg/m2 for 3 hours) + Carboplatin (AUC 5-6) for 6 cycles
• Docetaxel (75 mg/m2 for 2 hours) + Carboplatin (AUC5-6) for 6 cycles
 Special Clinical Situations

Options for Early Stages: Options for Advanced Stages:

1. Re-explore and surgically stage 1. Re-explore and do debulking
A. Inadequately
2. Chemotherapy surgery followed by
Staged Tumors
chemotherapy
2. Chemotherapy followed by IDS
1. Conservative surgery (USO, IO, PFC, complete surgical staging) is standard for
early stage.17
B. Ovarian
2. Conservative surgery, followed by antepartal chemotherapy (Cisplatin-
Cancer in
Cyclophosphamide) 18 for advanced disease beyond second trimester (Level 4)
Pregnancy
3. Completion surgery postpartum for advanced diseases or for early stages not
desirous of pregnancy

III. RECURRENT DISEASE

1. Taxane + Carboplatin 21 (Level 1b)

Platinum Sensitive
2. Single agent Carboplatin or Cisplatin 1, 22 ( Level 1b)
(disease-free interval ≥ 6
3. Gemcitabine + Carboplatin 23 ( Level 1b)
months)
4. Pegylated Liposomal Doxorubicin + Carboplatin (ref) (Level 2b)
1. Oral Etoposide 26, 27 ( Level 2b) 5. Tamoxifen 30 ( Level 1a)
24
Platinum Refractory 2. Taxanes ( Level 2b) 6. Gemcitabine 28, 29 ( Level 2b)
(disease-free interval < 3. Liposomal Doxorubicin ( Level 1b) 7. Capecitabine 31 ( Level 2b)
6months) 4. Topotecan 25 ( Level 1b) 8. Vinorelbine 32 ( Level 2b)
9. Bevacizumab (ref) (Level 2b)

FOLLOW-UP
After completion of treatment, recommended follow-up is as follows:
a. Every 3 months for 4 visits, every 4 months for 3 visits, every 6 months for 6 visits,
then annually thereafter.
b. Determination of appropriate tumor markers every visit.
c. Transvaginal ultrasound color Doppler studies every 4-6 months
d. 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.

IV. SEX CORD STROMAL TUMORS

STAGE STATUS INTERVENTION ADJUVANT THERAPY

USO, IO, PFC, complete surgical
IA Young/desirous of pregnancy
staging
None 7, 8 ,9 (Level 1a)
Reproductive function not
THBSO, IO, PFC, complete staging
desired
1. Chemotherapy*
Optimally or Sub-optimally THBSO, IO, PFC, Complete surgical
IB - II (optional)
debulked staging
2. Pelvic EBRT
Optimally or Sub-optimally 1. Chemotherapy*
III - IV THBSO, IO ± Tumor Debulking
debulked 2. WART
 Special Clinical Situations

A.
1. Re-explore and surgically stage
Inadequately
2. Chemotherapy*
Staged Tumors
1. Conservative surgery (USO, IO, PFC, complete surgical staging) is standard for
early stage.17
B. Ovarian
2. Conservative surgery, followed by antepartal chemotherapy* for advanced
Cancer in
disease beyond second trimester
Pregnancy
3. For advanced stage, completion surgery post-partum should be performed.
4. For early stage, choice of completion surgery or close follow-up (?)

FOLLOW-UP

• Complete physical examination

• Determination of appropriate tumor markers every 4-6 months
• Transvaginal ultrasound +/- color Doppler studies as necessary
• Annual CT, chest X-ray (discretionary)
• Hormonal replacement therapy

V. GERM CELL TUMORS

STAGE STATUS INTERVENTION ADJUVANT THERAPY

Young/desirous of USO*, IO, PFC, complete For all tumors other than pure
pregnancy staging dysgerminoma and low-grade
IA, G1 (grade I) immature teratoma,
Reproductive function not THBSO, IO, PFC, complete
chemotherapy is given 29, 31
desired staging
(Level 3a)
Young/desirous of USO*, IO, PFC, complete
IA G2,G3 pregnancy staging ± tumor debulking 1. Chemotherapy**
II – III Reproductive function not THBSO, IO, PFC, complete 2. EBRT for Dysgerminoma
desired staging ± tumor debulking
Young/desirous of
USO*, IO ± Tumor Debulking
pregnancy23 30
IV Chemotherapy** (Level 2b)
Reproductive function not THBSO, PO ± Tumor
desired Debulking

Special Clinical Situations

1. Re-explore and surgically stage

A. Inadequately Staged
2. Chemotherapy**
Tumors
3. Radiation Therapy for dysgerminoma
1. Conservative surgery (USO, IO, PFC, complete surgical staging) is
standard for early stage.17
B. Ovarian Cancer in 2. Conservative surgery, followed by antepartal chemotherapy** (BEP)
17
Pregnancy for advanced disease beyond second trimester (Level 4)
3. Completion surgery post-partum for advanced diseases or for early
stages not desirous of pregnancy

FOLLOW-UP
• Complete physical examination
• Determination of appropriate tumor markers every 3 months
• Transvaginal ultrasound +/- color Doppler studies as necessary
• Annual CT, chest X-ray (discretionary)
• Hormonal replacement therapy
VULVAR CANCER

I. INCIDENCE
• 1.2 to 2.1/100,000 women
• accounts for 3-5% of all genital tract cancers
• PGH incidence: 2.5% (as of 1990)
• peak age – 65-75 years
• 15% occur in women less than 40 years old

II. RISK FACTORS (more common in the type I vulvar cancers)

• Age (postmenopausal)
• Smoking
• History of abnormal pap smear
Smoking + history of abnormal Pap smear increases risk for vulvar cancer 35-fold
• Human Papilloma Virus infection – HPV 16, sometimes HPV 33, 6
• Sexually-transmitted diseases (HSV, condyloma acuminata)
• Suggested associations with hypertension, diabetes mellitus, obesity – may simply be
co-existing medical conditions common to the aging process

Table 1: Relative Risks of vulvar cancer by selected risk factors

Risk Factor
History of abnormal pap smear 1.41
History of genital warts / HPV infection 15
Current smoker 2.03
Relative Risk

III. PRIMARY PREVENTION

• Smoking cessation
• Prevention of sexually-transmitted diseases
Total sexual abstinence
Lifetime mutual monogamy
• Prophylactic HPV vaccination
• Prompt and appropriate diagnosis and treatment of VIN
• Prompt and appropriate diagnosis and treatment of lichenoid pattern vulvar
dermatosis
• Routine gynecoloic examination should include thorough inspection of the external
genitalia
o Careful inspection of the vulva when Pap Smear is performed (frequency of Pap
Smear as recommended in cervical cancer screening guidelines)

IV. SECONDARY PREVENTION

• No routine screening is recommended

V. CLINICAL PRESENTATION
Early
• Vulvar pruritus and irritation
• Vulvar mass or lesion (may be leukoplakic, velvety, erythematous, ulcerated or
pigmented)
• Bleeding, pain or discharge

Late
• Groin discomfort or palpable groin nodes may indicate lymph node involvement
 • Bladder and bowel symptoms when these organs are involved

VI. DIAGNOSTICS
• Complete history and physical examination - assessment of primary tumor (extension
to adjacent bony or mucosal structures and involvement of inguinal lymph nodes)
• Evaluation of the cervix (including cervical cytology, colposcopy) and vagina
• Biopsy is mandatory to establish diagnosis
o Multiple biopsies are needed: center of lesion, normal surrounding skin,
underlying stroma
• Additional radiographic and endoscopic studies should be considered for those with
large primary tumors and suspected metastases (barium enema, cystourethroscopy,
proctosigmoidoscopy, CT scan, fine needle aspiration biopsy, intravenous
pyelography)
o CT scan or MRI is helpful in detecting inguinal and pelvic lymph node involvement

VIII. BASIC WORKING KNOWLEDGE

A. Guidelines For Complete Surgical Staging

• Tumor assessment is based on physical examination and biopsy with endoscopic
assessment in cases of bulky disease
• Nodal status is determined by surgical evaluation of the groins
• The presence or absence of distant metastases is based on a diagnostic work-up
tailored to the patient’s clinical presentation

B. 2009 FIGO Staging

STAGE I Tumor confined to the vulva or perineum, no nodal metastasis

IA Tumor 2 cm or less, with stromal invasion < 1 mm
IB Tumors > 2 cm or stromal invasion > 1 mm
STAGE II Tumor of any size with extension to adjacent perineal structures (lower
1/3 of urethra, vagina, anus), negative nodes
STAGE III Tumor of any size with or without extension to adjacent perineal
structures with positive inguinofemoral lymph nodes (LN)
IIIA (1) 1 LN metastasis (> 5 mm)
(2) 1-2 LN metastases (< 5 mm)
IIIB (1) > 2 LN metastasis (> 5 mm)
(2) > 3 LN metastasis (< 5 mm)
IIIC Positive lymph nodes with extracapsular spread
STAGE IV Tumor invades other regional or distant structures
IVA Tumor invades upper urethral and/or vaginal mucosa, bladder mucosa,
rectal mucosa, pelvic bone; or fixed or ulcerated inguinofemoral node
IVB Any distant metastasis, including pelvic lymph nodes

C. WHO HISTOPATHOLOGIC CLASSIFICATION

I. Epithelial neoplasms of skin and mucosa

A. Invasive Squamous cell carcinoma
1. Keratinizing
2. Non-keratinizing
3. Basaloid carcinoma
4. Verrucous
5. Warty carcinoma [condylomatous]
B. Basal cell carcinoma
 C. Adenocarcinoma
II. Bartholin gland carcinomas
A. Squamous cell carcinoma
B. Adenocarcinoma
C. Adenoid cystic carcinoma
D. Adenosquamous carcinoma
E. Transitional cell carcinoma
F. Undifferentiated
III. Carcinoma and Sarcoma of ectopic breast tissue
IV. Carcinoma of sweat gland origin
V. Soft tissue sarcomas
A. Embryonal rhabdomyosarcoma (sarcoma botryoides)
B. Leiomyosarcoma
C. Malignant fibrous histiocytoma
D. Epithelioid sarcoma
E. Aggressive angiomyxoma
F. Dermatofibrosarcoma protuberans
G. Epithelioid sarcoma
H. Malignant rhabdoid tumor
I. Malignant nerve sheath tumor
J. Angiosarcoma
K. Kaposi sarcoma
L. Hemangiopericytoma
M. Liposarcoma
N. Alveolar soft part sarcoma
O. Other sarcomas (Enzinger & Weiss or WHO)
VI. Other malignant tumors
A. Malignant melanoma
B. Endodermal sinus tumor (yolk sac tumor)
C. Neuroectodermal tumors (Merkel cell)
D. Lymphomas
E. Others
VII. Secondary and Metastatic tumors
VIII. Unclassified tumors

SGOP TREATMENT GUIDELINES

MANAGEMENT OF EARLY PRIMARY TUMOR (Stage IA-II)

NODES CLINICALLY NEGATIVE (Level 2b)
TREATMENT
Lesion > 2 cm • Radical local excision with bilateral inguino-femoral
lymphadenectomy
Lesion ≤ 2 cm
- If stromal invasion > • Radical local excision with unilateral inguino-femoral
1mm lymphadenectomy unless if:
1. Within 1 cm of midline
2. Labia minora involved
3. Ipsilateral positive nodes
• Otherwise, Radical local excision with bilateral inguino-
femoral lymphadenectomy*
- If stromal invasion ≤ • Complete excision of the lesion to allow serial sectioning
1 mm and proper assessment of depth of invasion
• > 1 mm invasion – Manage as above
• ≤ 1 mm invasion – Radical local excision
*Triple incision technique to decrease morbidity
ADJUVANT TREATMENT FOR EARLY PRIMARY TUMOR WITH POOR PROGNOSTIC FACTORS
HISTOLOGIC POOR RISK FACTORS ADJUVANT
LYMPH NODE STATUS Bilateral pelvic and inguinal radiotherapy
1. Macrometastasis (> 5 mm)
2. Extracapsular spread
3. > 2 nodes with micrometastasis (< 5
mm)
PRIMARY TUMOR Bilateral pelvic and inguinal radiotherapy
1. (+) lines of resection
2. surgical margins < 8 mm
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 or:
palpable lymphadenectomy* 1. Macrometastasis (> 5 mm)
2. Extracapsular spread
3. > 2 nodes with
micrometastasis (< 5 mm)
• Bilateral pelvic and inguinal
radiotherapy

If histopath NEGATIVE or only 1

microscopically positive node
• Observation
Suspicious groin nodes Resection of macroscopic
groin nodes followed by
frozen section
If FS POSITIVE: • Bilateral pelvic and inguinal
• Resect any macroscopic radiotherapy
pelvic nodes seen on CT
scan and defer
complete
lymphadenectomy
If FS NEGATIVE: If definitive histopath is
• Complete the inguino- POSITIVE:
femoral • Bilateral pelvic and inguinal
lymphadenectomy radiotherapy

If definitive histopath is
NEGATIVE or 1 microscopically
positive node:
• Observation
Fixed or ulcerated groin If resectable:
nodes • Resection of all • Bilateral pelvic and inguinal
macroscopic groin radiotherapy
 nodes and any enlarged
pelvic nodes on CT scan
If unresectable:
• Preoperative • Post-operative resection of
radiotherapy + macroscopic residual disease
chemotherapy
(Cisplatin + 5-FU or
Carboplatin)42

II. PRIMARY LESION (Level 2b)

PRIMARY TREATMENT ADJUVANT

Tumor resectable without Radical tumor resection If margin positive or ≤ 8 mm:
requiring stoma • Post-operative
radiotherapy
If > 8 mm:
• Observe
Resection would require Pre-operative radiotherapy
stoma + chemotherapy (more
limited resection of tumor
bed)

TUMOR RECURRENCE
Local vulvar Options: (Level 3b)
recurrence 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.

VULVAR MELANOMA

CLARK’S PRIMARY TREATMENT ADJUVANT

LEVEL
I-V • For tumor < 1 mm thick: wide local 1. Alpha interferon
excision with at least 1 cm surgical 2. Immunotherapy (Dendritic immuno-
margin therapy)
• For intermediate thickness 3. Interleukin-2
melanoma (1-4 mm): wide local 4. Chemotherapy
excision with at least 2 cm surgical Options:
margins. a) Dacarbazine (DTIC)
• Regardless of the thickness, in all b) DTIC + Interferon-alpha
cases it is necessary to include at c) Dartmouth Regimen
least a 1 cm deep margin extending d) Temozolomide
through the subcutaneous fat to the
muscular fascia below (Level 3b)
 • Lymph node biopsy for staging or
lymphadenectomy for therapeutic
reasons have no proven benefit in
female genital tract melanomas.
(Level 3b)

PAGET'S DISEASE OF THE VULVA

GENERAL GUIDELINES

1. Up to 10–15% of cases of vulvar Paget’s 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
• Wide local excision with removal of underlying dermis, in the absence of clinical or
histologic evidence of invasive carcinoma. (Level 3b)
• Removal of a small amount of subcutaneous tissue to rule out an underlying occult
adenocarcinoma.
• 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).

• 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

BARTHOLIN’S GLAND CARCINOMA

TREATMENT
Surgical management of Bartholin’s carcinoma is similar to that of squamous cell carcinoma:
• 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)
• Radical vulvectomy with bilateral groin node dissection for lesions > 2 cm or encroaches
 on the midline. (Level 2b)
• Radical local excision for adenoid cystic lesions. (Level 2b)

If a tumor is deemed to be unresectable:

• 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:
• Positive or close margins
• Positive inguinal femoral lymph nodes
• Adenoid cystic lesions with positive margins or perineural invasion

BASAL CELL CARCINOMA OF THE VULVA

TREATMENT
• Wide local excision with at least 1 cm margin. (Level 3b)
VAGINAL CANCER

• INCIDENCE

• 0.42/100,000 women 1
• accounts for 2% of all genital tract cancers2
• peak age incidence -7th decade of life2

II. RISK FACTORS

• Age (postmenopausal)
• History of vulvar or cervical intraepithelial neoplasia or cancer
• Previous exposure to diethylstilbestrol (DES)
• Prior hysterectomy for preinvasive or invasive cervical disease
• Previous abnormal Pap smears

III. PRIMARY PREVENTION

• Prevention of sexually-transmitted disease

IV. SECONDARY PREVENTION

• No routine screening test is recommended

• Careful inspection of the vagina when Pap smear is performed (frequency
of Pap smear as recommended in cervical cancer screening guidelines)

*Regular cytologic screening for women with a history of prior surgery or radiation therapy
for preinvasive or invasive cancer of the vulva/ cervix

V. CLINICAL PRESENTATION
Early
• Mostly asymptomatic
• Vaginal discharge or postcoital bleeding
• Vaginal lesion or mass
Late
• Groin discomfort or palpable groin nodes may indicate lymph node
involvement
• Bladder and bowel symptoms when these organs are involved

VI. DIAGNOSTICS
• Complete History and Clinical Examination
• Biopsy
• Metastatic work-up: Chest X-ray, Intravenous Pyelogram, Cystoscopy,
Proctosigmoidoscopy, Barium enema, CT Scan, MRI

VIII. BASIC WORKING KNOWLEDGE

A. Guidelines For Complete Surgical Staging

• Staging is best performed with the patient under anesthesia

• Additional biopsy specimens of the vagina should be taken at various sites
to determine the limits of abnormal vaginal mucosa
 • Colposcopic evaluation of the cervix is mandatory to rule out primary
cervical tumor

B. FIGO STAGING

Stage 0: Carcinoma in situ (preinvasive carcinoma)

Stage I: Tumor confined to the vagina
Stage II: Tumor invades the paravaginal tissues but does not extend to the pelvic wall
Stage III: Tumor extends to the pelvic wall
Stage IVA: Tumor invades mucosa of bladder or rectum and/or extends beyond the true
pelvis
Stage IVB: Distant metastasis

C. WHO HISTOLOGIC CLASSIFICATION

• Epithelial Tumors
• Squamous
• Squamous intraepithelial tumors (VAIN)(1)
• mild dysplasia (VAIN 1)
• moderate dysplasia (VAIN 2)
• severe dysplasia/carcinoma in situ (VAIN 3)
• Invasive squamous cell carcinoma
• Keratinizing
• Nonkeratinizing
• Verrucous
• Warty (condylomatous)
• Glandular lesions
• Mullerian papilloma
• Adenosis, with or without atypia
• Adenocarcinoma
• Clear cell
• Endocervical type
• Endometrioid type
• Intestinal type
• Mesonephric
• Other invasive tumors
• Adenosquamous carcinoma
• Adenoid cystic carcinoma
• Carcinoid tumor
• Small cell carcinoma
• Undifferentiated carcinoma

• Mesenchymal tumors
• Leiomyosarcoma
• Sarcoma botryoides (embryonal rhabdomyosarcoma)
• Endometrioid stromal sarcoma
• Other

• Mixed epithelial and mesenchymal tumors

• Mixed tumor
• Adenosarcoma
• Malignant mesodermal mixed tumor
• Tumor resembling synovial sarcoma
 • Other
• Malignant melanoma
• Yolk sac tumor (endodermal sinus tumor)
• Lymphoma/leukemia

• Metastatic tumor

D. TREATMENT

TREATMENT OF VAGINAL INTRAEPITHELIAL NEOPLASIA

Biopsy

Invasive
Cancer
Preinvasive Disease

Treat Accordingly
Wide local excision with or without skin grafting
• Partial or total vaginectomy with skin grafting for multifocal or extensive
disease
• Laser therapy
• Intravaginal chemotherapy with 5% fluorouracil cream
• Brachytherapy (6000-7000cGy) to the entire vaginal mucosa

Stage I or II
Lesion < 2 cm
Lesion > 2 cm
Radiation Therapy:

Interstitial and / or Intracavitary

with
External beam radiation therapy
Stage III
Stage IV
 Localized
Stage IVA
Metastatic
Stage IVB
Rarely, surgery may be combined with radiotherapy
Chemotherapy
+
Palliative Radiation