Neoadjuvant chemotherapy versus primary surgery in patients with stage III/IV endometrial cancer: A National Cancer Database study.
Authors: Cummings Mackenzie , Nicolais Olivia , Banks Joshua , Keith Scott W. , Burton Elizabeth , Shahin Mark S. , Sorosky Joel I. , Edelson Mitchell 
Published: June 2024

5603 Background: The current treatment recommendation for advanced endometrial cancer is primary cytoreductive surgery, if feasible, or neoadjuvant chemotherapy (NACT) followed by surgery. To date, no randomized trials have compared these approaches in patients with stage III/IV endometrial cancer, and there is limited evidence or guidance for using NACT. The objectives of this study were to assess the national trend over time in the rates of primary surgery versus NACT in advanced endometrial cancer and to compare patient characteristics, outcomes, and complications between cohorts to provide insight into patient selection for either treatment paradigm. Methods: The National Cancer Database (NCDB) was queried for patients diagnosed with stage III/IV endometrial cancer between 2004 to 2019. Cohorts included primary surgery followed by chemotherapy, NACT followed by surgery, and chemotherapy alone. The primary outcome was the annual rate of primary surgery versus NACT followed by surgery over the study duration. Secondary outcomes were length of stay, 30-day readmission rate, and 30- and 90-day mortality following surgery. Patient characteristics, readmission rates, and mortality were compared using Chi-squared tests. A Wilcoxon Rank Test was used to assess the length of stay. Results: 23,155 patients met inclusion criteria. 3,268 received NACT followed by surgery, 13,161 received primary surgery, and 6,726 received chemotherapy alone. Age, race, ethnicity, median income, distance to a hospital, and comorbidities were similar between cohorts. The proportion of patients receiving NACT followed by surgery increased from 10.4% to 22.8%. Those undergoing primary surgery decreased from 51.7% to 40.6%. Patients receiving NACT were more likely to be stage IVB (61.0% vs. 32.70%), have serous histology (32.2% vs. 20.2%) and have public insurance (51.3% vs. 46.9%). Patients receiving NACT were less likely to be stage III (33.2% vs. 63.6%), and have endometrioid histology (37.3% vs. 47.6%). The length of stay following surgery was not significantly different between cohorts. Unplanned 30-day readmissions were higher in the primary surgery cohort (4.4% vs. 3.0%, p<0.001). 30-day mortality (0.9% vs. 0.2%, p<0.001) and 90-day mortality (5.5% vs. 2.2%, p<0.001) were higher in the NACT cohort. Conclusions: In advanced endometrial cancer, the utilization of NACT has increased nationally over the last two decades, while primary surgery has declined. Unplanned admissions were higher in the primary surgery group, but unexpectedly 30- and 90-day postoperative mortality were higher in the NACT group. Formal phase III trials to assess NACT vs surgery should be planned in patients with advanced endometrial cancer. Further research is necessary to determine baseline differences between cohorts in order to identify which patients would benefit from a neoadjuvant chemotherapy strategy.