A. E. Rosenthal1,2, N. Posever1,2, A. Wiechert1,2, K. M. Esselen1,2, and J. W. Jang1,2; 1Beth Israel Deaconess Medical Center, Boston, MA, 2Harvard Medical School, Boston, MA
Purpose/Objective(s):Our study evaluates outcomes of Stage III endometrial cancer patients treated with upfront chemotherapy with or without subsequent radiation (“upfront” cohort) compared to radiation with concurrent sensitizing cisplatin with or without subsequent chemotherapy (“concurrent” cohort). Our objective was to assess differences in 1)recurrence free survival (RFS) and overall survival (OS); 2) initial recurrence site; and 3) acute and long-term toxicities.Materials/
Methods: All stage III endometrial cancer patients treated at our institution from 2010-2021 were included in chart review.Univariate analyses were performed using Mann-Whitney U, Fisher’s exact, and logrank tests. Multivariate analysis was done using Cox proportional hazards and binomial regression models. Results: Our sample included 156 patients; 107 received upfront and 49 received concurrent treatment. Groups were balanced in age, race, BMI, and comorbidities. More patients in the upfront cohort had stage IIIC2 disease (28% vs 14%, p=0.04), and high-grade histology (54% vs 6%, p<0.01). Median RFS for all patients was 35 months, and median OS was 48 months. In the upfront vs concurrent groups, median RFS was 26 vs 50 months (p<0.01) while median OS was 42 vs 56 months (p<0.01). When adjusting for stage and histology, the upfront group had a trend towards shortened RFS (p=0.09), and significantly shortened OS with a hazard ratio of 4.2 (95% CI 1.1 to 15.9). There was no significant difference in site of initial recurrence between groups. For patients with endometrioid histology, 49 patients received upfront and 44 received concurrent treatment. After adjusting for stage and histology, in the upfront group, there was a trend towards shortened RFS (p=0.05), and significantly shortened OS with a hazard ratio of 9.2 (95% CI 1.4 to 61.1). Patients in the upfront group were more likely to have initial pelvic or paraaortic nodal recurrence (p=0.04).More patients in the concurrent group discontinued one agent during subsequent chemotherapy due to toxicity (p<0.05), but no difference was seen in chemotherapy delays, dose reductions or early discontinuation. Upfront patients had more vulvar/anal pain (q=0.01) and urinary frequency (q=0.01), but there were no differences between groups in grade 3 or higher toxicities. Conclusion: Stage III endometrial cancer patients undergoing concurrent treatment trended toward improved RFS and had significantly longer median OS as compared to patients receiving upfront treatment, particularly among patients with endometrioid histology. For endometrioid patients, the upfront group had increased risk of nodal recurrence, but no difference was observed in local or distant recurrence. These findings suggest that there may be some stage III endometrial cancer patients who benefit from concurrent chemoradiation, which should be considered in future clinical trial design.
