Chemotherapy for Endometrial Cancer in Adjuvant and Advanced Disease Settings

: Level I evidence exists for use of adjuvant chemotherapy in stage IIIC endometrial cancer (positive lymph nodes), although results of randomized trials have varied. Chemotherapy is also often recommended for high-risk subsets of stage I disease, such as serous carcinomas, although prospective trial data to validate this practice are lacking. Carboplatin plus paclitaxel is the current standard regimen, based on extrapolation of data from the metastatic setting. Several clinical trials have compared adjuvant pelvic radiotherapy alone to a combination of radiotherapy and chemotherapy with mixed results. One of the largest of these trials, Postoperative Radiation Therapy in Endometrial Carcinoma 3 (PORTEC-3), has completed accrual and is awaiting data maturation. Metastatic disease is not curable. For tumors of low-grade endometrioid histology with a prolonged time to recurrence, endocrine therapy with a progestin-based regimen is appropriate. Chemotherapy will be used in most other cases, and the standard first-line regimen is carboplatin and paclitaxel. Few chemotherapy agents have been shown to produce meaningful response rates in the second-line setting. Molecularly targeted therapies such as mTOR inhibitors and antiangiogenic agents including bevacizumab have been studied but their role in the armamentarium remains uncertain.

Implications for practice: Following surgical resection and staging for endometrial cancer, adjuvant chemotherapy with carboplatin and paclitaxel can be administered to patients with a high risk for recurrence. This includes patients with stage IIIC disease with positive lymph nodes, and high-risk subsets of stage I disease such as serous carcinomas. In the metastatic setting, endocrine therapy can be considered, particularly for patients with lower-grade disease and a prolonged time to recurrence. Combined therapy with carboplatin and paclitaxel is the standard of care used for front-line chemotherapy. Antiangiogenic agents are clearly active, but how they should be integrated into treatment is not yet determined. Immunotherapy is a promising direction for patients with mismatch repair-deficient or polymerase ε-mutated tumors.