Endometrial Cancer

Abstract

Overview Endometrial carcinoma is the most frequent gynecologic cancer in the United States with over 65,000 new cases diagnosed per year. Over 80% have the classic estrogen‐dependent endometrioid histology with a favorable prognosis. Nonendometrioid histology types, including uterine serous carcinomas (USC), carcinosarcomas, and clear cell carcinomas, have a different molecular profile associated with more virulent disease and diminished survival. The Cancer Genome Atlas (TCGA) has defined four molecular subtypes of endometrial cancer, based on somatic mutations, copy number alterations, and microsatellite instability status. Over 75% of patients present with irregular or post‐menopausal bleeding. Surgical staging includes a hysterectomy, bilateral salpingo‐oophorectomy, with or without pelvic and para‐aortic lymph node sampling done via a laparotomy, laparoscopy, or robotic surgery. Surgery, where possible, constitutes the definitive primary treatment for most patients with endometrial carcinoma. Primary radiation therapy and primary hormonal therapy are alternatives for inoperable patients. Adjuvant therapy for stage I disease is determined by age, depth of myometrial invasion, lymph‐vascular space invasion, and tumor grade. For patients with advanced and recurrent disease radiation therapy, chemotherapy, and hormonal therapy are utilized. The combination of paclitaxel and carboplatin is the most effective and tolerable chemotherapy combination and currently serves as the backbone for a number of investigational strategies. Immune check‐point inhibitors are FDA approved for the treatment of metastatic endometrial cancer, including pembrolizumab alone for microsatellite instability‐high (MSI‐H) cancers and pembrolizumab and lenvatinib for microsatellite stable (MSS) disease. The growing understanding of the molecular aberrations common in endometrial cancer has led to exploration of a number of therapies, targeting angiogenesis and the PI3K/AKT, HER2, RAS/RAF, and DNA damage repair pathways.