Objective To investigate whether performing a lymph node dissection during hysterectomy improves overall survival in patients with clinical stage III endometrial cancer who received neoadjuvant chemotherapy.

Methods The National Cancer Database was queried to identify all patients with clinical stage III endometrial cancer who had undergone pre-operative chemotherapy as first course of treatment followed by hysterectomy with or without lymph node dissection between the years 2004 and 2020. Univariable and multivariable models were performed to investigate prognostic factors on overall survival.

Results This study analyzed 2882 patients with clinical stage III endometrial cancer who received upfront chemotherapy. Among those who underwent lymph node dissection, 38% had positive lymph nodes. Factors found to be independently associated with improved survival included lymph node dissection (p<0.001), adjuvant radiation (p<0.001), histology (p<0.001), tumor grade (p<0.001), pathologic node status (p<0.001), age (p<0.001), type of insurance (p=0.027), and race (p<0.001). Patients who underwent lymph node dissection at time of hysterectomy had a significantly better overall survival (107 vs 85 months; p<0.001). Multivariate and propensity score analyses robustly demonstrated that lymph node dissection significantly improved overall survival (HR 0.69, 95% CI 0.57 to 0.84, p<0.001), even among patients with pathologically negative lymph nodes.

Conclusion Our study suggests that performing lymph node dissection at the time of hysterectomy is associated with improved overall survival in all patients with stage III endometrial cancer who receive upfront chemotherapy, regardless of age, race, insurance status, histologic subtype, tumor grade, pathologic node status, adjuvant radiation or chemotherapy. Notably, patients with high-risk disease may particularly benefit from this approach.

Data are available in a public, open access repository. The data analyzed in this retrospective study were obtained from the National Cancer Database (NCDB), a joint project of the American College of Surgeons Commission on Cancer and the American Cancer Society: https://www.facs.org/quality-programs/cancer-programs/national-cancer-database/. The NCDB is a hospital-based registry that captures data on patient demographics, primary tumor characteristics, treatment delivered, and patient outcomes for a large, representative sample of newly diagnosed cancer patients in the USA. Due to the privacy restrictions mandated by the NCDB and its participating institutions, the data used in this project cannot be shared publicly. However, researchers interested in reproducing our study may contact the American College of Surgeons and inquire about access to the NCDB: https://www.facs.org/quality-programs/cancer-programs/national-cancer-database/.