Carcinoma of the endometrium is the most common female pelvic malignancy. Approximately 40,300 new cases are diagnosed yearly, although in most (75%), tumor is confined to the uterine corpus at diagnosis and therefore most can be cured. The 7,000 deaths yearly make uterine cancer only the eighth leading cause of cancer death in females. It is primarily a disease of postmenopausal women, although 25% of cases occur in women <age 50 and 5% <age 40. The disease is common in Eastern Europe and the United States and uncommon in Asia.
Phenotypic characteristics and risk factors common in patients with endometrial cancer include obesity, altered menstruation, low fertility index, late menopause, anovulation, and postmenopausal bleeding. Exposure to unopposed estrogen from either endogenous or exogenous sources may play a central etiologic role. Women taking tamoxifen for breast cancer treatment or prevention have a twofold increased risk.
Endometrial carcinoma occurs most often in the sixth and seventh decades of life. Symptoms often include abnormal vaginal discharge (90%); abnormal bleeding (80%), which is usually postmenopausal; and leukorrhea (10%). Evaluation of such patients should include a history and physical and pelvic examinations followed by an endometrial biopsy or a fractional dilation and curettage. Outpatient procedures such as endometrial biopsy or aspiration curettage can be used but are definitive only when positive.
Between 75 and 80% of all endometrial carcinomas are adenocarcinomas, and the prognosis depends upon stage, histologic grade, and extent of myometrial invasion. Grade I tumors are highly differentiated adenocarcinomas, grade II contain some solid areas, and grade III tumors are largely solid or undifferentiated. Adenocarcinoma with squamous differentiation is seen in 10% of patients; the most differentiated form is known as adenoacanthoma, and the poorly differentiated form is called adenosquamous carcinoma. Other less common pathologies include mucinous carcinoma (5%) and papillary serous carcinoma (<10%). This latter type has a natural history similar to ovarian carcinoma and should be managed as an ovarian cancer. Rarer histologies include secretory (2%), ciliated, clear cell, and undifferentiated carcinomas.
The staging of endometrial cancer requires surgery to establish the extent of disease and the depth of myometrial invasion. Peritoneal fluid should be sampled; the abdomen and pelvis explored; and pelvic and para-aortic lymphadenectomy performed depending upon the histology, grade, and depth of invasion in the uterine specimen on frozen section. After evaluation and staging, 74% of patients are stage I, 13% are stage II, 9% are stage III, and 3% are stage IV. Five-year survival by stage is as follows: stage I - 89%, stage II - 80%, stage III - 30%, and stage IV - 9% (
Patients with uncomplicated endometrial carcinoma are effectively managed with total abdominal hysterectomy and bilateral salpingo-oophorectomy. Pre- or postoperative irradiation has been used, and although vaginal cuff recurrence is reduced, survival is not altered. In women with poor histologic grade, deep myometrial invasion, or extensive involvement of the lower uterine segment or cervix, intracavitary or external beam irradiation is warranted.
About 15% of women have endometrial carcinoma with extension to the cervix only (stage II), and management depends upon the extent of cervical invasion. Superficial cervical invasion can be managed like stage I disease, but extensive cervical invasion requires radical hysterectomy or preoperative radiotherapy followed by extrafascial hysterectomy. Once disease is outside the uterus but still confined to the true pelvis (stage III), management generally includes surgery and irradiation. Patients who have involvement only of the ovary or fallopian tubes generally do well with such therapy (5-year survivals of 80%). Other stage III patients with disease extending beyond the adnexa or those with serous carcinomas of the endometrium have a significantly poorer prognosis (5-year survival of 15%).
Patients with stage IV disease (outside the abdomen or invading the bladder or rectum) are treated palliatively with irradiation, surgery, and/or progestational agents. Progestational agents produce responses in about 25% of patients. Well-differentiated tumors respond most frequently, and response can be correlated with the level of progesterone receptor expression in the tumor. The commonly used progestational agents hydroxyprogesterone (Dilalutin), megastrol (Megace), and deoxyprogesterone (Provera) all produce similar response rates, and the antiestrogen tamoxifen (Nolvadex) produces responses in 10 to 25% of patients in a salvage setting.
Chemotherapy is not very successful in advanced endometrial carcinoma. The most active single agents with consistent response rates of ≥20% include cisplatin, carboplatin, doxorubicin, epirubicin, and paclitaxel. Combinations of drugs with or without progestational agents have generally produced response rates similar to single agents.
Revision date: June 21, 2011
Last revised: by Janet A. Staessen, MD, PhD