Survival and Safety Outcomes of Three-Cycle Adjuvant Chemotherapy in Intermediate-Risk Endometrial Cancer

Objective: The optimal adjuvant therapy for intermediate-risk endometrial cancer remains controversial. Although radiotherapy is commonly used in Western countries, chemotherapy is preferred in Japan; however, its real-world outcomes remain limited. This study evaluated the survival and safety outcomes of three-cycle adjuvant chemotherapy in patients with intermediate-risk endometrial cancer. Methods: We retrospectively analyzed patients who underwent primary surgery for endometrial cancer at a university hospital between 2008 and 2019. Low- and intermediate-risk patients defined by the 2013 Japan Society of Gynecologic Oncology recurrence risk classification were included. Intermediate-risk patients were classified as receiving chemotherapy (Int-Chemo+) or not (Int-Chemo-). The primary endpoint was disease-free survival (DFS); secondary endpoints included cancer-specific survival (CSS), adverse events, and treatment completion. Results: Among 232 patients, 161 were low-risk and 71 intermediate-risk; 49 intermediate-risk patients received platinum-based combination chemotherapy. The 5-year DFS rates were 92.8% (95% CI, 88.6-96.9) in the low-risk group, 89.4% (95% CI, 80.7-98.2) in the Int-Chemo+ group, and 73.5% (95% CI, 53.5-93.6) in the Int-Chemo- group (log-rank p = 0.005). DFS differed between the Int-Chemo+ and Int-Chemo- groups (HR 0.232, 95% CI 0.062-0.867), whereas the DFS outcomes of the Int-Chemo+ group were numerically similar to those of the low-risk group. CSS did not differ significantly among groups (p = 0.052). Treatment completion was 93.8%, and grade ≥ 3 adverse events were mainly hematologic, without severe late toxicities. Conclusions: Three cycles of adjuvant platinum-based combination chemotherapy for intermediate-risk patients may be associated with improved DFS, while maintaining a high treatment completion rate and manageable toxicity.