Treatment of node-positive endometrial cancer: chemotherapy, radiation, immunotherapy, and targeted therapy

The standard of treatment for node-positive endometrial cancer (FIGO Stage IIIC) in North America has been systemic therapy with or without additional external beam radiation therapy (RT) given as pelvic or extended field RT. However, this treatment paradigm is rapidly evolving with improvements in systemic chemotherapy, the emergence of targeted therapies, and improved molecular characterization of these tumors. The biggest question facing providers regarding management of stage IIIC endometrial cancer at this time is: what is the best management strategy to use with regard to combinations of cytotoxic chemotherapy, immunotherapy, other targeted therapeutics, and radiation that will maximize clinical benefit and minimize toxicities for the best patient outcomes? While clinicians await the results of ongoing clinical trials regarding combined immunotherapy/RT as well as management based on molecular classification, we must make decisions regarding the best treatment combinations for our patients. Based on the available literature, we are offering stage IIIC patients without measurable disease postoperatively both adjuvant chemotherapy and IMRT with carboplatin, paclitaxel, and with or without pembrolizumab/dostarlimab as primary adjuvant therapy. Patients with measurable disease post operatively, high risk histologies, or stage IV disease receive chemoimmunotherapy, and vaginal brachytherapy is added for those with uterine risk factors for vaginal recurrence. In the setting of endometrioid EC recurrence more than 6 months after treatment, patients with pelvic nodal and vaginal recurrence are offered IMRT and brachytherapy without chemotherapy. For measurable recurrence not suitable for pelvic radiation alone, chemoimmunotherapy is preferred as standard of care.