Endometrial cancer

Abstract

Endometrial carcinoma is the most frequent gynecologic cancer in the USA. Over 80% of patients have type I cancers with the classic estrogen-dependent endometrioid histology. Type II cancers have a different molecular profile associated with more virulent disease and diminished survival and includes uterine serous papillary carcinomas and clear cell carcinomas. The Cancer Genome Atlas 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 postmenopausal bleeding. Surgical staging includes a total hysterectomy, bilateral salpingo-oophorectomy, and pelvic and para-aortic lymph node sampling which can be performed 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. Paclitaxel (T), carboplatin (C), cisplatin (P), and doxorubicin (A) are the most active single agents with TC and TAP being the most effective combination chemotherapy regimens. Hormonal therapy includes oral progestins, the progesterone-containing intrauterine device, tamoxifen, gonadotropin-releasing hormone analogs, and aromatase inhibitors. Emerging biologic agents with activity include bevacizumab and mammalian target of rapamycin (mTOR) inhibitors. Tumor molecular profiling, minimal invasive surgery, sentinel lymph node assessment, and integration of novel biologic therapies are likely to have a greater role in the future.