Carcinoma of the endometrium is the most common invasive gynecologic neoplasm in women in the United States. Over 30,000 new cases will be diagnosed this year. The hallmark of the therapeutic management of patients with endometrial carcinoma is hysterectomy. Appropriate determination of stage or extent of disease at the time of diagnosis is of critical importance because both extent of treatment and prognosis are strongly dependent on stage. Adjuvant irradiation has been used in many settings over the past century.

Overview of Treatment Strategies

In contradistinction to research in carcinoma of the uterine cervix, empiric studies in patients with endometrial carcinoma indicated that irradiation alone was not optimal therapy. The best clinical outcomes for patients with endometrial carcinoma seem to be achieved with either surgery alone or a combination of surgery and irradiation. In the past, irradiation was often administered in the preoperative setting. At present, irradiation alone is rarely administered; preoperative irradiation is given only in selected cases, with postoperative irradiation administered most commonly.

Following a preoperative work-up that usually includes a physical examination, routine blood work, chest x-ray, and ECG, the patient with endometrial cancer undergoes an exploratory laparotomy with hysterectomy, lymph node sampling, and peritoneal cytology. Omental biopsies should be performed if any areas seem suspicious for tumor. These data provide the basis for administering adjuvant therapy.

After surgery, further treatment with radiation may be indicated based on the surgical/pathologic staging information. Radiotherapy may be administered locally in the vagina, to the pelvis, or to the whole abdomen. Local irradiation to the vagina may be delivered in the inpatient setting using low-dose-rate brachytherapy or in the outpatient setting using high-dose-rate brachytherapy. Pelvic irradiation is administered as external irradiation alone or with the addition of vaginal brachytherapy. Radiation to the abdomen can be given as external irradiation or with intraperitoneal P-32. Postoperative chemotherapy is being evaluated in clinical trials.

For some patients with serious medical conditions, radiation therapy is used as an alternative to surgery. Severe cardiopulmonary disease and morbid obesity are the primary reasons for a patient with endometrial carcinoma to forgo surgery. Patients who do not undergo surgery are clinically staged and may receive internal, external, or combination radiotherapy, depending on patient and tumor characteristics.

Preoperative intracavitary brachytherapy, external irradiation, or both are administered to patients with high-grade lesions or advanced-stage disease. Radiation therapy is also used in patients with recurrent disease after surgery, and palliative radiation is administered to relieve symptoms.

Approaches to Staging

The International Federation of Gynecology and Obstetrics (FIGO) defined a clinical staging system for endometrial carcinoma in 1971.[1] It was revised in 1989,[2] and is now a surgical, rather than a clinical, staging system. Under the guidelines of the clinical staging system, it was implied that all patients should undergo a dilatation and fractional curettage. The uterus was sounded and an examination was performed with the patient under anesthesia. About 75% to 80% of patients were described as having clinical stage I disease, and about 10% to 15% were found to have tumor spread beyond the uterus after pathologic evaluation of the surgical specimen.

The current surgical staging procedure requires that a peritoneal cytology specimen be obtained and that pelvic and para-aortic lymph node sampling be performed. Previously, these specimens were not routinely obtained. With the advent of surgical staging, more patients are now found to have disease outside the uterus. Hence, a smaller percentage have true stage I disease. It is, therefore, difficult to compare the results of therapy for patients with endometrial cancer from one report to another, because there is no consistent definition of patient populations.

Despite the current recommendations for surgical staging, not all of the required specimens are obtained for all patients. Moreover, adjuvant postoperative therapy must be individualized and based on information that pertains to a specific patient.

Reviewing the Data

Few prospective randomized studies have been conducted in patients with endometrial carcinoma. However, in recent years, randomized studies have attempted to answer questions regarding the best management of these patients.

Outlined below are treatment recommendations for patients who are surgically staged and for those who undergo incomplete surgical staging. These recommendations are based on the results of prospective randomized studies, to the extent that they exist, and on the results of retrospective studies. Also described is the use of irradiation alone in medically inoperable patients and the use of irradiation in recurrent endometrial cancer after surgery alone, as well as palliative irradiation. Current prospective randomized studies will also be described.
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