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

Abstract

Opinion StatementThe 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.

Glycometabolism and lipid metabolism related genes predict the prognosis of endometrial carcinoma and their effects on tumor cells

“…Among them, Cisplatin exerts inhibitory effects on the DNA replication of EC cells, leading to detrimental consequences on the structural and functional integrity of DNA [ 62 , 66 ]. Paclitaxel exerts its effects by promoting the inhibition of tubulin polymerization and maintaining tubulin stability, thereby further suppressing tumor cell proliferation [ 67 ]. Tamoxifen, a nonsteroidal anti-estrogen drug, exerts its inhibitory effect on the proliferation of EC cells by competitively binding to estrogen receptors and antagonizing estrogen signaling [ 68 ].…”

Insights into MLH1 Methylation in Endometrial Adenocarcinoma through Pyrosequencing Analysis: A Retrospective Observational Study

“…In advanced cases, targeted therapies such as tyrosine kinase inhibitors and immunotherapies like PD-1/PD-L1 inhibitors may be employed. These treatments can specifically target cancer cells or enhance the immune system’s ability to recognize and destroy them, offering additional options when standard chemotherapy is insufficient [ 9 , 10 ].…”

Nanoparticle-Mediated Synergistic Chemoimmunotherapy for Cancer Treatment

“…https://doi.org/10.2147/IJN.S455213DovePressInternational Journal of Nanomedicine 2024:19 studies, the NCCN guidelines include the combination therapy of pembrolizumab/carboplatin/paclitaxel and dostarlimab/ carboplatin/paclitaxel as the first-class primary treatment option for stage III or IV endometrial cancer. July 31, 2023, the FDA approved dostarlimab in combination with carboplatin and paclitaxel for primary or recurrent mismatch repair deficiency (MMRd) EC 161. …”