Comparative analysis of adjuvant treatment outcomes in stage III endometrial cancer: overall survival, recurrence-free survival, site of primary recurrence, and toxicity.

Objective: Adjuvant treatment for stage III endometrial cancer remains controversial due to varying results from large randomized studies. Our objectives were to assess differences in (1) recurrence-free survival and overall survival, (2) initial recurrence site, and (3) acute and long-term toxicities in patients receiving chemotherapy vs chemoradiation as initial adjuvant treatment.

Methods: All stage III endometrial cancer patients treated at our institution from 2010 to 2021 were included. Treatment groups were defined as "chemo" if treated with upfront chemotherapy with or without subsequent radiation or "concurrent" if treated with chemoradiation with or without subsequent chemotherapy. Data were collected through retrospective chart review. Univariate analyses were performed using the Mann-Whitney U test, Fisher exact test, and log-rank test. Multivariate analysis was conducted using Cox proportional hazards and generalized linear regression models.

Results: A total of 156 patients were eligible for analysis. After adjusting for stage and histology, there was no difference in 5-year recurrence-free survival (HR 0.5, CI 0.22 to 1.11) with the chemotherapy group as reference. However, overall survival was improved in the concurrent group (HR 0.24 CI 0.06 to 0.90). When restricting the analysis to patients with endometrioid histology, overall survival was significantly improved in the concurrent group (HR 0.11, CI 0.16 to 0.73). In the full cohort, pelvic or para-aortic nodal recurrence (p = .01) and distant recurrence (p < .01) were significantly more likely in the chemotherapy group. There were no significant differences in high-grade toxicities.

Conclusions: Patients with stage III endometrial cancer who received upfront concurrent treatment had improved overall survival compared with those who received upfront chemotherapy, without significant differences in high-grade toxicities. These findings should be considered in the design of future clinical trials.