Standard treatment almost universally begins with a total hysterectomy (via any of a number of approaches—abdominal, vaginal, or minimally invasive) and removal of the remaining adnexal structures. Comprehensive staging, including pelvic and para-aortic lymph node assessment, is crucial in guiding postoperative adjuvant treatment (Table 29.3). EC spreads beyond the uterus by infiltrating directly through the myometrium, extending into the cervix or metastasizing, most often to the pelvic nodes and less frequently to the para-aortic nodes [3, 4].

Adjuvant postoperative treatment recommendations in advanced stage disease are widely disparate and an area of active research. However, assuming an adequate performance status, virtually all women with advanced stage disease (stage III and IV) will be recommended for chemotherapy, external beam pelvic radiotherapy with or without an extended para-aortic field, or some combination of both modalities. These treatments are geared at improving disease-free and overall survival in a population in whom overall survival remains disappointing—as low as 20 % in stage IV disease [7]. The role of surgical lymphadenectomy has been continuously debated since the FIGO staging criteria were adopted. Specifically, identifying which patients benefit from lymphadenectomy represents a unique challenge [4].

Type II EC-serous and clear cell carcinoma is biologically similar to high-grade serous carcinoma of ovary with high propensity for upper abdomen relapse. Currently, there is lack of prospective, randomized trials for type II EC. From available literature, there is suggestion that surgical staging should be performed even in the setting of minimally invasive/noninvasive disease. For all patients of type II EC-serous papillary or clear cell histology, chemotherapy should be included in both early stage and advanced disease. The role of radiation in combination is unclear and is currently being investigated in GOG 249 and GOG 258 protocols [8]. Currently, paclitaxel- and carboplatin-based protocol (similar to epithelial ovarian cancer) is being used [4–6].

Hormone therapy is effective in type I endometrial cancer (those with endometrioid histology); ER/PR status in metastatic disease predicts response to hormone therapy. Progestational agents that have been used in treatment of recurrent/metastatic disease include hydroxyl-progesterone, medroxyprogesterone, and megestrol. These agents produce a partial or complete response rate of 20–29 %. Long-term exposure to progestins leads to downregulation of ligand-dependent activation of PR and may lead to loss of response within the endometrium. In a Gynecology Oncology Group (GOG) study, 61 patients with advanced or recurrent uterine cancer were treated with a combination of megestrol and tamoxifen (antiestrogen). This strategy was based on hypothesis that intermittent exposure to progestins would permit tamoxifen to induce progesterone receptor and thus enhance effect of progestin therapy. The complete response rate was 21 %, and 5.4 % had a partial response. The average survival was 14 months. Toxicity was moderate and there were no treatment-related deaths. Of those who responded, 50 % sustained this response for an average of 20 months. It was noted that, overall, younger women had better responses to the treatment than older women [4, 5].