Incidence

Endometrial cancer is the most common malignancy of the female genital tract, accounting for approximately 30,000 new cases annually and 6,000 deaths. Endometrial cancer is the fourth most common malignancy in women behind breast, lung and colon cancer.

The median age at onset is 63 years with up to 25% of cases occurring in pre-menopausal women and 5% in patients younger than 40 years.

Risk Factors

The recognized risk factors often account for a chronic estrogenized state (endogenous and/or exogenous). These factors include nulliparity, early menarche, late menopause, obesity (35% of patients with endometrial cancer are not obese), chronic disease (e.g., diabetes, hypertension), unopposed estrogen therapy, and presence of atypical hyperplasia.

Pathology

The most common endometrial tumor histologies are:

1. Adenocarcinoma (75%)
2. Adenosquamous (18%)
3. Papillary Serous (6%)
4. Clear Cell (1%)

Routes of Spread

Endometrial cancer can spread by the following routes:

1. Direct extension to adjacent structures.
2. Trans-tubal passage of exfoliated cells.
3. Lymphatic dissemination.
4. Hematogenous dissemination.

Clinical Features

Abnormal uterine bleeding or post-menopausal bleeding are present in 90% of cases. Of interest, 15% of patients with post-menopausal bleeding have endometrial cancer. Other etiologies include atrophic vaginitis, exogenous estrogens, polyps, and other genital tract malignancy. Other associated nonspecific findings in patients with endometrial cancer include pyometria, hematometria, abnormal PAP smear, heavy menses and intermenstrual bleeding.

Pre-Treatment Work-Up

Patients suspected of having endometrial cancer should have pathologic confirmation of disease by either endometrial biopsy or dilation and currettage. Following confirmation of disease and careful physical exam the routine pre-operative evaluation consists of the following:

1. CXR
2. Blood tests which may include a CA-125.
3. Additional diagnostic tests may be performed if indicated.

Staging

Stage I: Carcinoma confined to the uterine corpus.

Ia- Tumor limited to the endometrium.
Ib- Invasion to less than one-half of the myometrium.
Ic- Invasion to more than one-half of the myometrium.

Stage II: The cancer has extended to the cervix but not outside the uterus.

IIa- Endocervical glandular involvement only.
IIb- Cervical stromal invasion.

Stage III: Extension of the tumor outside the uterus but confined to the true pelvis or para-aortic area.

IIIa- Tumor invades serosa and/or adnexa, and/or positive cytology.
IIIb- Vaginal metastasis.
IIIc- Metastasis to pelvic and/or para-aortic lymph nodes.

Stage IV: Distant metastasis or involvement of adjacent pelvic organs.

IVa- Invasion of the bowel or bladder mucosa.
IVb- Distant metastasis including intra-abdominal and/or inguinal lymph nodes. 

FIGO definition of grading:

G1 =  5% or less of a non-squamous or non-morular solid growth pattern.
G2 =  6-50% of a non-squamous or non-morular solid growth pattern.
G3 =  More than 50% of a non-squamous or non-morular solid growth pattern.

Treatment

A simplified approach to the treatment of patients with endometrial cancer can be achieved by subdividing the patients into high and low risk groups following hysterectomy and oophorectomy.

1. Disease confined to the uterus:

Sub-group 1: No further treatment (risk of recurrence<5%)
G1, G2 with less than 10% myometrial invasion
G3 with no myometrial invasion
No cervix invasion
Negative cytology
No lymph vascular invasion

Sub-group 2: Post-operative brachytherapy (risk of recurrence 5-10%)
G1, G2 with 10-50% myometrial invasion
G1, G2 with cervix invasion
Negative cytology

No lympho-vascular space invasion

Note: The occasional patient with extensive cervical involvement may be considered for radical hysterectomy.

Sub-group 3- Whole pelvis radiotherapy (risk of recurrence>10%)
All other cases of Stage I or Stage II disease.

2. Presence of extra-uterine disease:

Sub-group 1- Pelvic spread of disease:
Pelvic radiotherapy + vaginal brachytherapy and  possible extended field if positive common or para-aortic lymph node involvement.

Sub-group 2- Optimally debulked < 2cm residual disease confined to the abdominal cavity.
Whole abdominal radiation, chemotherapy and/or progestins.

Sub-group 3- Suboptimally debulked >2cm residual disease or disease outside the abdominal cavity.
Chemotherapy and/or progestins. Radiotherapy also may have a role in local control of tumor related symptoms.

Recurrent Disease: Treatment is dependent on the extent of recurrence. Isolated local recurrences in patients who have received prior radiotherapy may be considered for pelvic exenteration. Unfortunately these are unusual and recurrent disease most often is not amenable to surgery. The remaining options include radiotherapy (in patients who have not had previous treatment) or chemotherapy.

Prognostic Factors

The most important prognostic variable in endometrial cancer is the surgical stage. Other prognostic variables include myometrial invasion, vascular space invasion, nuclear grade, histologic type, tumor size, patient age, and peritoneal cytology.

Survival

Stage I- 75-100%
Stage II- 60%
Stage III- 50%
Stage IV- 20%

Recommended Follow-Up

Follow-Up every 3 months for the first 2 years,  every 6 months for years 3-5 and yearly thereafter.  Routine pelvic exam performed at each visit and PAP smear on yearly basis. Chest X-ray may also be considered on annual basis, but the yield is low in the absence of symptoms.