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Endometrial cancer is usually adenocarcinoma. Typically, postmenopausal vaginal bleeding occurs. Diagnosis is by biopsy. Staging is surgical. Treatment requires hysterectomy, bilateral salpingo-oophorectomy, usually pelvic and para-aortic lymph node dissection, and excision of all tissue likely to be involved. For advanced cancer, radiation, hormone, or cytotoxic therapy is usually indicated.

Endometrial cancer is more common in developed countries in which dietary fat is high. In the US, it is the 4th most common cancer in women, affecting 1 in 50.

Etiology and Pathology

Endometrial cancer affects mainly postmenopausal women, particularly those aged 50 to 65. Major risk factors are obesity, diabetes, and hypertension. Other risk factors include unopposed estrogen, tamoxifen Some Trade Names
NOLVADEX
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use for > 5 yr, previous pelvic radiation therapy, and a personal or family history of breast or ovarian cancer. Unopposed estrogen (high circulating levels of estrogen with no or low levels of progesterone) may be associated with obesity, polycystic ovarian syndrome, nulliparity, late menopause, estrogen-producing tumors, anovulation (ovulatory dysfunction), and estrogen therapy without progesterone. Heredity contributes to endometrial cancer in about 6% of cases, usually in families with hereditary nonpolyposis colorectal cancer (HNPCC) syndrome.

Endometrial cancer is usually preceded by endometrial hyperplasia. Adenocarcinoma accounts for > 80% of endometrial cancers. Other types include papillary serous, clear cell, squamous, and mucinous carcinoma.

The cancer may spread from the surface of the uterine cavity to the cervical canal; through the myometrium to the serosa and into the peritoneal cavity; via the lumen of the fallopian tube to the ovary, broad ligament, and peritoneal surfaces; via the bloodstream, leading to distant metastases; or via the lymphatics. The higher (more undifferentiated) the grade of the tumor, the greater is the likelihood of deep myometrial invasion, pelvic or para-aortic lymph node metastases, or extrauterine spread.

Symptoms and Signs

Most (> 90%) women have abnormal uterine bleeding (eg, postmenopausal bleeding, premenopausal recurrent metrorrhagia); ¹⁄₃ of women with postmenopausal bleeding have endometrial cancer. A vaginal discharge may occur weeks or months before postmenopausal bleeding.

Diagnosis

Endometrial cancer is suspected in women with postmenopausal bleeding, in premenopausal women with abnormal bleeding, in postmenopausal women with a routine Pap test showing endometrial cells, and in any women with a routine Pap test showing atypical endometrial cells. If cancer is suspected, outpatient endometrial biopsy is done; it is > 90% accurate. If results are inconclusive or suggest cancer, inpatient fractional D & C with hysteroscopy is done. An alternative is transvaginal ultrasonography, which may help in diagnosis.

Once cancer is diagnosed, pretreatment evaluation includes serum electrolytes, kidney and liver function tests, CBC, chest x-ray, and ECG. If an abdominal mass or hepatomegaly is detected during physical examination, or liver function tests are abnormal, pelvic and abdominal CT are also done to check for extrauterine or metastatic cancer.

Staging: Staging is based on histologic differentiation (grade 1 [least aggressive] to 3 [most aggressive]) and extent of spread, including invasion depth, cervical involvement (glandular involvement vs stromal invasion), and extrauterine metastases (see Table 2: Gynecologic Tumors: Staging of Endometrial Carcinoma*). Staging is surgical and includes peritoneal fluid cytology, exploration of the abdomen and pelvis, and biopsy or excision of suspect extrauterine lesions. Pelvic and para-aortic lymph nodes are removed. Surgical staging is done traditionally via laparotomy but may be done via laparoscopy.

Table 2
Staging of Endometrial Carcinoma* Stage† Definition I Confined to the uterine corpus IA Tumor limited to endometrium IB Invasion of < 1⁄2 myometrium IC Invasion of > 1⁄2 myometrium II Involvement of the uterus and cervix but no extension outside of the uterus IIA Involvement of endocervical glands IIB Invasion of cervical stroma III Extension beyond the uterus but not beyond the true pelvis IIIA Invasion of serosa, adnexa, or both and/or positive peritoneal cytologic results IIIB Metastases to vagina IIIC Metastases to pelvic or para-aortic lymph nodes or both IV Involvement of the bladder or intestinal mucosa or distant metastases IVA Invasion of bladder or intestinal mucosa or both IVB Distant metastases, including intra-abdominal or inguinal lymph nodes or both *Based on staging established by the International Federation of Gynecology and Obstetrics (FIGO) and American Joint Committee on Cancer (AJCC), 1989, 1992, and 1997. Endometrial cancer is usually surgically staged. †For all but stage IVB, grade (G) indicates percentage of tumor with a nonsquamous or nonmorular solid growth pattern: G1 (≤ 5%), G2 (6–50%), or G3 (> 50%). Nuclear atypia excessive for the grade raises the grade of a G1 or G2 tumor by 1. In serous adenocarcinomas, clear cell adenocarcinomas, and squamous cell carcinomas, nuclear grading takes precedence. Adenocarcinomas with squamous differentiation are graded according to the nuclear grade of the glandular component.

Prognosis and Treatment

Prognosis is worse with higher-grade tumors, more extensive spread, and older patient age. Average 5-yr survival rates are 70 to 95% with stage I or II and 10 to 60% with stage III or IV. Overall, 63% of patients are cancer-free ≥ 5 yr after treatment.

If cancer appears to be stage I/grade 1 without deep myometrial invasion, the probability of unrecognized lymph node metastasis is < 2%. Treatment is usually total hysterectomy and bilateral salpingo-oophorectomy via laparotomy or laparoscopy. For grade 1 with deep myometrial invasion and grade 2 or 3, complete pelvic and para-aortic lymphadenectomy is also done.

Stage II or III cancer requires pelvic radiation therapy with or without chemotherapy. Treatment of stage III cancer must be individualized, but surgery is an option; generally patients who undergo combined surgery and radiation therapy have a better prognosis. Except in patients with bulky parametrial disease, a total abdominal hysterectomy and bilateral salpingo-oophorectomy should be performed. Treatment of stage IV is variable and patient dependent but typically involves a combination of surgery, radiation therapy, and chemotherapy. Occasionally, hormonal therapy should also be considered.

Hormone therapy with a progestin causes regression for up to 3 yr in 35 to 40% of patients. Pulmonary, vaginal, and mediastinal metastases may regress. Treatment continues as long as the response is favorable.

Several cytotoxic drugs (particularly doxorubicin Some Trade Names
ADRIAMYCIN
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and cisplatin Some Trade Names
PLATINOL
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; paclitaxel Some Trade Names
TAXOL
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) are effective. With monthly regimens of doxorubicin Some Trade Names
ADRIAMYCIN
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60 mg/m² plus cisplatin Some Trade Names
PLATINOL
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60 mg/m² IV, overall response rate may be ≥ 50%.

Treatment of endometrial hyperplasia consists of progestins or surgery (eg, D & C), depending on the complexity of the lesion and the patient's desire to avoid hysterectomy.

Last full review/revision November 2005

Content last modified November 2005