Endometrial, Ovarian, and Cervical Cancer

Kristine Zanotti

Carcinoma of the endometrium

Definition
Endometrial cancer arises from the glandular tissue within the uterine lining.
Prevalence
Endometrial cancer is the most common of the gynecologic malignancies. Approximately 2% to 3% of
women in the United States will develop cancer of the endometrium at some point during their lives.
With an estimated 37,000 new cases last year, it is the fourth most common malignancy among
women. It predominantly affects older women, with 75% of cases occurring in the postmenopausal
years.
Pathophysiology
Endometrial cancer is a heterogeneous disease that is believed to have two biologically different
subtypes, implying two different mechanisms for its origin.

Low-Risk Subtype
The most common subtype is a well-differentiated carcinoma (grade 1 or 2 endometrioid histology)
that behaves in an indolent fashion, causes bleeding symptoms in its early stages, and is curable in
most cases. Risk factors for this low-risk subtype are well known and are related to an increase in
circulating estrogens: obesity, chronic anovulation and nulliparity, estrogen replacement therapy
(unopposed by progesterone), and tamoxifen use.

High-Risk Subtype
The high-risk subtype accounts for a minority of endometrial malignancies. These poorly differentiated
tumors (grade 3 endometrioid, clear cell, and papillary serous carcinoma) are not associated with
increased circulating estrogens. Rather, they appear to occur spontaneously in postmenopausal
women without clearly defined risk factors. These tumors metastasize early and account for a
disproportionate number of mortalities from endometrial malignancy. Modes of spread include local
invasion and lymphatic and vascular embolization. The most common metastatic sites include the
cervix, adnexa, and retroperitoneal lymph nodes.
Signs and Symptoms
Endometrial cancer usually manifests with abnormal uterine bleeding. It should be suspected in any
postmenopausal woman with bleeding symptoms. Pre- or perimenopausal women might have bleeding
abnormalities such as menorrhagia or metrorrhagia.

Less commonly, asymptomatic women can present with an abnormal Papanicolaou (Pap) smear
revealing atypical or malignant endometrial cells. A normal Pap smear in a symptomatic woman,
however, must never be relied on to exclude endometrial pathology.
Diagnosis
A complete physical examination is the first step in the evaluation of a woman with suspected
endometrial cancer. Inspection of the vulva, anus, vagina, and cervix is necessary to evaluate for
metastatic lesions. A biopsy should be done for any suspicious genital tract lesions detected on
examination. Bimanual and rectovaginal examination to evaluate the uterus, cervix, adnexa,
parametria, and rectum is essential. Palpation of the inguinal and supraclavicular nodes may reveal
enlargement in advanced cases with metastatic disease.
Histologic evaluation of endometrial tissue is necessary. An endometrial biopsy can be performed
safely and easily in the office setting in most symptomatic patients. The sensitivity for detecting
endometrial carcinoma approaches that of a dilation and curettage (D&C) and avoids the expense and
morbidity of an operative procedure. Several biopsy instruments are available for use, including the
Pipelle sampler and Novak curette.
Occasionally, D&C is necessary to obtain tissue for histologic evaluation. Cervical stenosis and patient
discomfort are common indications for D&C. This outpatient surgical procedure may be performed
using a paracervical block with sedation; however, in some cases, general or regional anesthesia may
be preferred. Hysteroscopy and saline infusion sonography visualize endometrial lesions, such as
polyps, within the uterine cavity and can be useful adjuncts to endometrial sampling techniques.
If endometrial cancer is confirmed, further studies are needed to optimize treatment planning,
including a chest x-ray to rule out metastatic disease. Other studies may be performed based on a
patient's risk factors and symptoms at presentation. These include computed tomography (CT) scans
of the abdomen and pelvis with oral and intravenous contrast (for preoperative assessment of
extrauterine tumor spread in high-grade endometrial malignancies); sigmoidoscopy, colonoscopy, or
barium enema; intravenous pyelogram; and serum cancer antigen 125 (CA 125) assay for papillary
serous carcinoma.
Treatment
Treatment is based on the surgically determined disease stage and on assessment of prognostic
features.1 Staging of endometrial cancer is defined by the International Federation of Gynecology and
Obstetrics (FIGO) criteria outlined inTable 1. Surgical staging by exploratory laparotomy requires a
peritoneal cytology assessment, intraoperative inspection of the abdominal and pelvic organs
(diaphragm, liver, omentum, pelvic and aortic lymph nodes, peritoneal surfaces) for evaluation of
metastatic disease, hysterectomy with bilateral salpingo-oophorectomy, and retroperitoneal lymph
node sampling.2
Table 1: FIGO Staging for Endometrial Carcinoma

Stage Definition
I

Carcinoma confined to the corpus uteri

II

Carcinoma that involves the corpus and the cervix but has not extended outside the uterus

III

Carcinoma that extends outside the uterus but is confined to the true pelvis and/or
retroperitoneal lymph nodes

IV

Carcinoma that involves the bladder or bowel mucosa or that has metastasized to distant
sites

FIGO, International Federation of Gynecology and Obstetrics.

Surgery
Although endometrial cancer is traditionally managed by laparotomy, increasing evidence supports the
safety and efficacy of laparoscopic hysterectomy in appropriately selected patients at low risk for
extrauterine tumor spread.

Adjuvant Treatment
The need for adjuvant therapy is based on disease stage and on risk factors for tumor recurrence.

Stage I Disease
For disease confined to the uterus, patients are placed in low-, intermediate-, and high-risk categories,
and adjuvant therapies are based on pathologic features. In general, stage I tumors that are higher
grade and more deeply invasive into the myometrium have a greater risk for recurrence and benefit
from adjuvant therapy postoperatively.
Whole-pelvis radiotherapy, with or without vaginal cuff brachytherapy, is the most commonly used
adjuvant postoperative treatment modality. Patients with the histologic variant papillary serous
carcinoma, an aggressive endometrial lesion with a high risk for extrapelvic recurrence, are generally
offered chemotherapy to reduce postoperative recurrence risk, although this treatment is
controversial.

Stage II Disease
For disease involving the uterine cervix, there are several treatment options. When unsuspected
cervical stromal involvement is found during surgery, postoperative external-beam radiotherapy with
vaginal cuff brachytherapy is indicated. If cervical involvement is known preoperatively, various
combinations of surgery and radiotherapy have been used:

Hysterectomy, bilateral salpingo-oophorectomy, and node sampling followed by postoperative

irradiation

Preoperative intracavitary and external-beam radiation therapy followed by hysterectomy and

bilateral salpingo-oophorectomy

Radical hysterectomy and pelvic lymphadenectomy

Unfortunately, there is no standard treatment for stage II endometrial cancer, and the equivalence of
these strategies has not been assessed in comparative randomized trials.

Stage III Disease

In general, postoperative whole-pelvis radiotherapy (vaginal cuff brachytherapy) is indicated when
disease involves adnexal structures or retroperitoneal nodes. Patients with para-aortic involvement
might benefit from extended-field radiotherapy.

Stage IV Disease
The site of metastatic disease and associated symptoms dictate the appropriate treatment of stage IV
endometrial cancer. For bulky pelvic disease, radiation therapy consisting of a combination of
intracavitary and external beam irradiation is used. When distant metastases are present, systemic
therapy is indicated. Satisfactory tumor responses to hormonal treatment with progestational agents
can often be achieved in well-differentiated (grades 1 and 2) tumors. Useful chemotherapeutic agents
include doxorubicin and paclitaxel.
Outcomes
Endometrial cancer is one of the most curable of the gynecologic cancers because most patients have
well-differentiated tumors and present with symptoms early in the disease process (Table 2). Five-year
survival rates are much poorer in patients with the less common and poorly differentiated tumor
histologies. These patients often present with metastatic disease and account for a disproportionate
number of endometrial cancer deaths.
Table 2: Endometrial Carcinoma: Stage at Presentation and 5-year Relative Survival Rate
Disease Extent

Stage Distribution (%)

Survival (%)

All stages

84

Localized

73

96

Regional

13

66

Distant

27

Unstaged

53

Adapted from Ries LAG, Kosary CL, Hankey BF, et al (eds): SEER Cancer Statistics Review, 19731995. Bethesda, National Cancer Institute, 1998.

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Cancer of the ovary

Definition
Ovarian cancer is a heterogeneous group of malignancies that arises from the various cell types that
compose the organ.

Epithelial
Nearly 90% of ovarian malignancies are classified as epithelial ovarian carcinomas. These cancers
arise from the germinal epithelium lining the ovary. Epithelial ovarian cancer can be further subdivided
into several histologic cell types: serous, mucinous, endometrioid, clear cell, transitional, and
undifferentiated carcinomas. The risk of epithelial ovarian cancer increases with age and is found
predominantly in postmenopausal women. Epithelial tumors of low malignant potential (borderline
ovarian carcinoma) are a histologic variant that is less aggressive than their invasive epithelial
counterparts, are found in younger women, and are often confined to the ovary at diagnosis.

Germ Cell
Germ cell tumors account for approximately 5% of all ovarian cancers and recapitulate the developing
embryo or placental structures. Histologic subtypes include dysgerminoma (most common),
endodermal sinus tumor, immature teratoma, choriocarcinoma, and embryonal carcinoma. Germ cell
ovarian cancer can occur in women of any age, but approximately 80% of these are diagnosed in
women younger than 30 years.

Sex CordStromal
Sex cordstromal tumors, which account for approximately 5% of all ovarian cancers, develop in the
connective tissue and supporting ovarian stroma. These tumors are generally less aggressive and
often produce steroid hormones, including estrogen, progesterone, and testosterone. Some patients
with hormone-producing tumors present with signs and symptoms of steroid excess, such as vaginal
bleeding or hyperandrogenism.
Prevalence
According to the American Cancer Society, there were more than 23,000 new cases of ovarian cancer
and 14,000 deaths from the disease in the United States in 2001. It is estimated that a woman has
a 1% to 2% lifetime risk for developing ovarian cancer. Ovarian carcinoma is the fifth most frequent
cause of cancer death in women, and one half of all cases occur in women older than 65 years.
Pathophysiology
The cause of ovarian cancer is poorly understood; however, risk factors and mode of spread have
been well described.

Risk Factors

The most significant risk factor for ovarian cancer is a positive family history. When two or more firstdegree relatives have or have had ovarian cancer, a woman's lifetime risk for developing this cancer is
7%. If a heritable cancer syndrome is identified, this lifetime risk can increase 17- to 50-fold. Three
dominantly inherited mutations are known to be associated with the development of approximately
10% of all ovarian carcinomas: breast-ovarian cancer syndrome, which is associated with mutations
in BRCA-1 and BRCA-2 genes; site-specific ovarian carcinoma; and hereditary nonpolyposis colorectal
cancer (Lynch syndrome II), which is associated with mutations in mismatch repair genes. Advanced
age is also associated with increased risk, whereas high parity, oral contraceptive use, tubal ligation,
and hysterectomy decrease one's risk.

Mode of Spread
Ovarian cancer usually spreads via cellular shedding into the peritoneal cavity followed by implantation
on the peritoneal surface. Local invasion of the bowel and bladder is common in advanced cases.
Tumor cells also may block diaphragmatic lymphatics. The resulting impairment of lymphatic drainage
of the peritoneum is believed to play a role in development of ascites in ovarian cancer.
Transdiaphragmatic spread and seeding of the pleura with pleural effusion are also common in
advanced cases.
Signs and Symptoms
Unfortunately, most patients with epithelial ovarian cancer experience few or no symptoms until the
disease has widely metastatasized. Manifesting symptoms usually relate to an increasing intraabdominal tumor burden and ascites and are often vague, mimicking other more common diseases.
Symptoms include fatigue; bloating or a feeling of fullness; abdominal swelling or pain; early satiety;
vague but persistent gastrointestinal complaints, such as gas, nausea, and indigestion; frequency or
urgency of urination; change in bowel habits; unexplained weight loss or gain; shortness of breath;
and obstructive symptoms, such as nausea, vomiting, and constipation or obstipation.
On the other hand, borderline, germ cell, and sex cordstromal tumors are often confined to the ovary
at the time of diagnosis. They may be quite large at presentation, and associated symptoms may be
related to their large size. These masses are occasionally detected during the screening pelvic
examination. More commonly, patients feel the mass themselves or present with symptoms of acute
abdomen due to torsion of the adnexa or rupture of the tumor.
Diagnosis
A complete physical examination is the first step in the diagnosis of ovarian cancer. Although pelvic
examination is notoriously inefficient at detecting presymptomatic early ovarian cancer, a pelvic mass
can often be palpated on examination in symptomatic patients. The finding of a unilateral or bilateral
nonmobile (fixed) mass is characteristic of epithelial ovarian carcinoma. Cul-de-sac masses may also
be palpated with rectovaginal examination. Impingement of the rectum and compromise of lumen
diameter can also be appreciated on this examination. Abdominal distention due to ascites is another
common finding. The distended abdomen is dull to percussion and an omental cake may be palpated

in the upper abdomen. Further diagnostic workup is necessary to establish extent of disease and
exclude other causes of an adnexal mass, carcinomatosis, or ascites.

Imaging Studies
Transvaginal ultrasound uses higher-frequency sound waves to image the ovaries, allowing improved
morphologic characterization. The addition of color flow Doppler can further characterize the mass. A
vascular mass with low resistive indices supports a diagnosis of malignancy. Chest x-ray might
indicate pleural effusion, which is common in patients with ovarian carcinomatosis. CT scans of the
abdomen and pelvis with intravenous and oral contrast characterize tumor burden and assist in
evaluating other causes of adnexal mass, carcinomatosis, or ascites. Other studies may be performed
based on a patient's risk factors and symptoms at presentation. These include sigmoidoscopy,
colonoscopy, or barium enema; upper gastrointestinal endoscopy; and intravenous pyelogram.

Serum Tumor Markers

Serum tumor markers can assist in preoperative evaluation; however, their limitations must be
understood so they are not misinterpreted or obtained inappropriately. Serum testing is essential to
monitoring treatment response for ovarian cancer, but its usefulness as a diagnostic tool is hindered
by poor sensitivity and specificity. CA 125 is a high-molecular-weight glycoprotein that is expressed by
more than 80% of nonmucinous epithelial ovarian cancers. Although elevated in most women with
advanced ovarian cancer, only 50% of patients with early-stage disease have an elevated CA 125, and
mucinous epithelial ovarian cancers express this antigen poorly. Furthermore, an elevated CA 125 is
not specific for ovarian cancer. Many nongynecologic and benign gynecologic conditions also are
associated with elevations in this serum antigen.
If nonepithelial ovarian cancer is suspected, other tumor markers may be useful to assist in
diagnosis. Alpha fetoprotein, human chorionic gonadotropin, and lactic dehydrogenase may be
expressed by germ cell malignancies. If metastatic colon or pancreatic carcinoma is suspected, serum
carcinoembryonic antigen and CA 19-9 might also be elevated. Limitations in the sensitivity and
specificity of these tests must be understood so they can be interpreted appropriately for each
patient.

Paracentesis
Malignant ascites is common in patients with metastatic epithelial ovarian carcinoma. However,
ascites due to other conditions such as congestive heart failure and cirrhosis must be ruled out by
careful history and, if necessary, diagnostic testing.
Although paracentesis may be performed for cytologic examination, diagnostic paracentesis is not
necessary for most patients if they have already been deemed appropriate for exploratory surgery and
operative management. Furthermore, a negative cytology from preoperative paracentesis does not
exclude the possibility of malignancy, and differentiating the site of tumor origin is rarely possible on
cytologic examination. Large-volume therapeutic paracentesis, however, may be useful for palliation of

symptoms of abdominal distention and associated respiratory compromise due to diaphragmatic

elevation.

Consultation
If a reasonably high probability for ovarian malignancy exists, consultation with a gynecologic
oncologist is essential to ensure appropriate preoperative counseling and preparation, operative
management, and postoperative care.
Treatment
Ovarian cancer is initially managed with exploratory laparotomy to confirm the diagnosis and determine
the extent of disease (surgical staging) and for tumor cytoreduction.

Histologic Identification
The availability of reliable intraoperative frozen section is essential for optimal surgical decision
making and management. For example, fertility-sparing surgery may be an option in select ovarian
malignancies, such as germ cell tumors. In addition, although tumor debulking appears to have
survival benefit in patients with ovarian malignancies, carcinomatosis related to an extraovarian
primary tumor does not necessarily benefit from such measures.

Surgical Staging
Accurate staging determines both treatment and prognosis. Inadequate surgical staging is a common
problem in patients with presumed early-stage disease when the operating surgeon does not perform
the necessary procedures for adequate staging. Therefore, it is imperative that the operating surgeon
is familiar with staging criteria and has the surgical skills necessary to perform all the necessary steps
of the staging procedure. FIGO staging criteria are described in Table 3.
Table 3: FIGO Staging for Ovarian Cancer
Stage Definition
I

Growth limited to the ovaries

II

Growth involves one or both ovaries with pelvic extension

III

Tumor with peritoneal implants outside the pelvis, or positive retroperitoneal or inguinal
nodes, or both

IV

Tumor involves one or both ovaries with distant metastasis

FIGO, International Federation of Gynecology and Obstetrics.

Cytoreduction
Metastatic implants of ovarian cancer typically involve the peritoneal surfaces and are often amenable
to resection along with the primary tumor mass. Although not documented by any randomized clinical

trial, optimal tumor cytoreduction (defined as removal of the primary tumor and all gross metastatic
implants to less than 1 cm residual in largest diameter) is believed to improve chemotherapy
response and disease-free survival.3 To achieve these goals, surgical techniques such as en bloc
hysterectomy with resection of the rectosigmoid, small bowel, total omentum, spleen, and possibly
more may be necessary.
Aggressive resection of tumor does not appear to have any clinical advantage unless all metastatic
implants also can be optimally reduced. The operating surgeon must exercise judgment as to whether
optimal tumor reduction is possible and can be safely achieved without incurring significant
complications that would delay chemotherapy.

Adjuvant Treatment
Most, but not all, ovarian cancer patients require adjuvant chemotherapy after surgery. The importance
of adequate surgical staging is evident when making decisions regarding adjuvant therapy in stage I
disease. Most chemotherapy can be given on an outpatient basis, although some regimens are given
over a period of several days, requiring hospitalization.
For epithelial ovarian cancer, platinum-based therapy-either cisplatin or carboplatin-in combination with
paclitaxel has demonstrated the highest activity of all agents studied.4 These agents are generally
given intravenously every 3 weeks for a total of six courses. One study, however, suggests that
continuation of single-agent paclitaxel for 12 courses is associated with an improved disease-free
survival. Although its impact on overall survival is uncertain, these findings have the potential to
significantly affect recommended adjuvant therapy for this disease.

Stage I Disease
Patients with stage Ia or Ib tumors that are well-differentiated (grade 1) have an excellent prognosis,
and the addition of adjuvant chemotherapy has not been demonstrated to improve survival in these
patients. However, caution must be exercised when considering withholding adjuvant therapy in
patients with presumed stage I disease who have not had the benefit of adequate surgical staging.
Reoperation for staging purposes is an option in these patients. Patients with grades 2 and 3 tumors
are at increased risk for recurrence and appear to benefit from adjuvant chemotherapy.

Stages II to IV Disease
The use of adjuvant chemotherapy has survival and palliative benefits in patients with metastatic
ovarian carcinoma and a larger tumor burden. Adjuvant therapy for tumors of borderline histology is
generally not indicated. Little evidence exists that postoperative chemotherapy or radiation therapy
alters the course of these tumors in any beneficial way.
All patients with germ cell tumors, except those with stage I, grade 1 immature teratoma and stage IA
dysgerminoma, require postoperative chemotherapy.5 With platinum-based combination chemotherapy,
the prognosis for patients with endodermal sinus tumors, immature teratomas, embryonal

carcinomas, choriocarcinomas, and mixed tumors containing one or more of these elements has
improved dramatically.
Most patients with advanced ovarian cancer ultimately develop progressive or recurrent disease after
initial surgery and adjuvant chemotherapy and require some form of palliative therapy. Patients with
recurrent ovarian carcinoma are considered either platinum sensitive or platinum resistant, depending
on whether the response duration was less than or longer than 6 months from prior therapy with a
platinum-based agent. Potentially platinum-sensitive patients often benefit from re-treatment with a
platinum-based agent. Owing to its favorable toxicity profile, carboplatin is ideally suited for palliative
therapy in the appropriate patient.
Platinum-resistant patients, on the other hand, generally have more limited responses to alternative
chemotherapeutic agents. A number of second-line chemotherapeutic agents might have palliative
benefit, including paclitaxel, liposomal doxorubicin, topotecan, and gemcitabine. Because of poorer
response rates in most patients with platinum-resistant disease, participation in clinical trials
evaluating new therapies is also appropriate.
When disease-related symptoms can be palliated, such as the reversal of intestinal obstruction,
surgical intervention might improve the quality of life. However, palliation is rarely achieved in
advanced disease when there are multiple areas of partial or complete obstruction or when the transit
time is prolonged due to diffuse peritoneal carcinomatosis.
Outcomes
Survival in ovarian cancer is related to surgical stage and tumor histology (Table 4). Patients with
borderline tumors, germ cell malignancies, and sex cordstromal tumors often present with earlierstage disease and generally have improved prognoses.
Table 4: Ovarian Carcinoma: Stage at Presentation and 5-Year Relative Survival Rate
Disease Extent

Stage Distribution (%)

Survival (%)

All stages

50

Localized

25

95

Regional

79

Distant

61

28

Unstaged

29

Adapted from Ries LAG, Kosary CL, Hankey BF, et al (eds): SEER Cancer Statistics Review, 19731995. Bethesda: National Cancer Institute, 1998.
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Cancer of the cervix

Definition
Cervical carcinoma has its origins at the squamocolumnar junction or the cervix. The precursor lesion
is dysplasia or carcinoma in situ (cervical intraepithelial neoplasia III). Squamous cell carcinoma
accounts for 90% and adenocarcinoma accounts for 10% of cervical cancers.
Prevalence
Last year, cervical cancer was diagnosed in approximately 14,000 women in the United States, and
there were 4,700 deaths from the disease. Peak incidence of cervical carcinoma is at 51 years of
age, whereas that for carcinoma in situ is approximately 10 years younger.
Pathophysiology
Epidemiologic studies convincingly demonstrate that the major risk factor for preinvasive or invasive
cervical carcinoma is infection with the human papillomavirus (HPV). HPV DNA is detected in virtually
all cervical cancers, with HPV subtypes 16, 18, and 31 identified most commonly. Other known risk
factors include early age at first intercourse, number of sexual partners, and a positive smoking
history.
Cervical carcinoma spreads predominantly by local invasion and lymphatic metastasis. The most
common metastatic sites include the vagina, parametrium, and pelvic lymph nodes.
Signs and Symptoms
Precancerous changes of the cervix rarely cause symptoms and are generally detected by pelvic
examination and Pap smear screening. Symptoms usually do not appear until lesions become
cancerous and invade underlying cervical stroma. Postcoital vaginal spotting may be one of the first
symptoms of the disease. Ultimately, an enlarging and vascular tumor mass can become ulcerated,
leading to frank vaginal bleeding, heavy vaginal discharge, or both. As the tumor invades locally or
spreads into the regional lymphatics, patients develop pain, lower extremity edema, and lower
extremity deep venous thrombosis.
Diagnosis
Cervical cancer may be detected in its early stages by the screening Pap smear or by identification of
larger lesions in the symptomatic patient. The Pap smear is a screening test only. Patients whose Pap
smears indicate cytologic abnormalities suggestive of high-grade lesions are at risk for invasive cancer
and warrant further diagnostic testing with colposcopy. Ablative procedures should not be performed
without a thorough colposcopic examination.
Colposcopy is a technique of visually evaluating the cervix for abnormalities. The colposcope is a
magnifying device that aids the examination of the cervix. Light filters and staining solutions are used
in combination to identify cervical dysplasia. If an abnormality is identified, a biopsy may be

recommended. Treatment is usually based on the results of the biopsy. Referral to an expert familiar
with the colposcopy technique and the treatment of cervical dysplasia is recommended.
When a colposcopic abnormality or a grossly visible cervical lesion is identified, a biopsy is necessary
for histologic evaluation. Pap smear cytology is not adequate for diagnosis. Cervical biopsy may be
accomplished in an office setting using any number of instruments, such as the Tischler-Morgan,
Kevorkian, and mini-Townsend biopsy instruments or even a loop electrode.
With documented invasive cervical carcinoma, further diagnostic workup is necessary to establish the
extent of disease. Cervical cancer staging is defined clinically by FIGO criteria using physical
examination and a limited number of diagnostic studies (Table 5).
Table 5: FIGO Staging for Cervical Cancer
Stage Definition
0

Preinvasive disease (carcinoma in situ)

Carcinoma strictly confined to the cervix

II

Carcinoma that extends into the parametrium (but not onto the pelvic sidewall) or the upper
two thirds of the vagina

III

Carcinoma that has extended onto the pelvic sidewall or involves the lower one third of the
vagina. All cases with a hydronephrosis or nonfunctioning kidney should be included, unless
they are known to be due to other causes.

IV

Carcinoma that has extended beyond the true pelvis to distant organs or has clinically
involved the mucosa of the bladder, rectum, or both

FIGO, International Federation of Gynecology and Obstetrics.

A pelvic examination is necessary to assess tumor size and configuration and to identify possible
vaginal metastasis and parametrial or pelvic sidewall involvement. Additionally, lymphatic metastasis
is common in advanced cervical cancer. Assessment of groin and supraclavicular lymph nodes might
reveal enlargement. Lower extremity edema might also be present with an expanded tumor diameter,
significant pelvic lymphadenopathy, or both. Homans' sign or a palpable cord may be identified if there
is an associated deep venous thrombosis.
Chest x-ray can identify pulmonary metastasis. Computed tomography of the abdomen and pelvis (with
oral, rectal, and intravenous contrast) allows for more complete assessment of tumor extent within
the abdomen and pelvis. Although not part of FIGO clinical stage criteria, it is useful for treatment
planning. An intravenous pyelogram may be obtained if ureteral obstruction or bladder involvement is
suspected. Cystoscopy or sigmoidoscopy may be obtained if bladder involvement, rectal involvement,
or both are suspected.

Treatment
Treatment and prognosis of cervical cancer are greatly affected by the extent of disease at the time of
diagnosis.

Stage 0 Disease (Carcinoma in Situ)

Invasive cervical carcinoma must be excluded with confidence before therapy for preinvasive disease
is undertaken. Standard treatment options include excisional and ablative therapy. In general,
excisional therapies are preferred because they are associated with a lower failure rate and provide
tissue for histologic evaluation to assess margins and exclude invasion. Excisional therapies include
the loop electrosurgical excision procedure (LEEP), laser conization, cold knife conization, and
extrafascial hysterectomy. Ablative therapies include cryotherapy and laser ablation therapy.
In most cases, outpatient LEEP is preferred.6 LEEP uses a fine wire loop with electrical energy flowing
through it to remove the transformation zone of the cervix or focal areas of dysplasia. It can quickly
and easily be performed in an office setting and generally requires only local anesthesia, thus avoiding
the risks associated with general anesthesia. Cold knife or laser conization require general
anesthesia.

Stage Ia1 (Microinvasive Cervical Cancer)

Cervical cancer in its earliest stages of invasion is termed microinvasive carcinoma. It is defined as
invasion of the stroma no greater than 3 mm deep and no wider than 7 mm in diameter with no lymphvascular space involvement.
Disease meeting this strictly defined criteria has a very limited risk for lymphatic metastasis, and
outcome is excellent with less-radical therapies. Expert pathology review is essential when considering
less radical therapies for disease qualifying as microinvasive. Equivalent treatment options include
extrafascial hysterectomy, cervical conization, and intracavitary radiation alone (without external beam
radiotherapy).

All Other Stage I and Stage IIa Disease

Risk for lymphatic metastasis is increased with larger and more deeply invasive lesions. For this
reason, radical therapies are necessary, and referral to a qualified gynecologic oncologist is
appropriate and recommended.
Therapy selection depends on patient factors, tumor factors, and surgical expertise. Radical
hysterectomy with bilateral pelvic lymphadenectomy is one option; combined external beam
radiotherapy and brachytherapy with concurrent chemotherapy is an equivalent option.
Several randomized phase III trials have shown an overall survival advantage for cisplatin-based
therapy given concurrently with radiation therapy. As a result of these findings, the National Cancer
Institute issued a clinical announcement suggesting that 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.7

Stages IIb to IVa Disease

With tumor spread beyond the cervix and upper vagina, cure rates for radical surgery decline. Stages
IIb to IVa cervical cancer are best treated by radiation therapy using combined external beam pelvic
radiation and concurrent cisplatin-based chemotherapy with intracavitary brachytherapy or interstitial
therapy.

Stage IVb Disease

Patients with distant metastasis are no longer amenable to cure by radiation therapy. Unfortunately,
response rates to standard chemotherapy are generally less than 20% and are typically brief. All
patients with distant metastasis or recurrent disease should be considered appropriate candidates for
phases I and II clinical trials investigating new treatments.
Palliative treatment options include radiation therapy to relieve pelvic disease and chemotherapy with
agents such as cisplatin, ifosfamide, paclitaxel, gemcitabine, and irinotecan. 8
Outcomes
If not diagnosed in its early stages, cervical cancer carries high mortality (Table 6). Properly diagnosed
and managed, tumor control of in situ cervical carcinoma should be nearly 100%.
Table 6: Cervical Carcinoma: 5-Year Relative Survival Rate
Disease Extent

Survival (%)

All stages

84

Localized

96

Regional

66

Distant

27

Adapted from Ries LAG, Kosary CL, Hankey BF, et al (eds): SEER Cancer Statistics Review, 19731995. Bethesda, National Cancer Institute, 1998.
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Summary

Endometrial cancer is one of the most curable of the gynecologic cancers because most
patients have well-differentiated tumors and present with symptoms early in the disease
process.

A woman's lifetime risk for developing ovarian cancer is 7% when two or more first-degree
relatives have this cancer. This lifetime risk can increase 17- to 50-fold if a heritable cancer
syndrome is identified.

Unfortunately, most patients with epithelial ovarian cancer experience few or no symptoms until
the occurrence of widespread metastatic disease.

Serum tumor markers can assist in the preoperative evaluation of ovarian cancer; however,
their limitations must be understood so they are not misinterpreted or obtained inappropriately.

Epidemiologic studies convincingly demonstrate that the major risk factor for preinvasive or
invasive cervical carcinoma is infection with the human papillomavirus (HPV).

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