Resectability-driven surgical management in advanced endometrial cancer: Survival outcomes after primary and delayed cytoreduction.

INTRODUCTION: Although complete cytoreduction is consistently associated with improved outcomes in advanced endometrial cancer (EC), the optimal treatment strategy and the role of delayed cytoreductive surgery remain poorly defined. MATERIALS AND METHODS: This retrospective single-center study included consecutive patients with FIGO 2023 stage IIIB2, bulky IIIC, or IV treated between 2005 and 2025. Patients underwent primary debulking surgery (PDS) or were initially allocated to a medical treatment strategy; selected responders underwent interval debulking surgery (IDS) following reassessment of resectability. Progression-free survival (PFS) and overall survival (OS) were assessed using Kaplan-Meier and Cox regression analyses. RESULTS: Seventy-six patients met the inclusion criteria: 30 treated with PDS, 17 undergoing IDS, and 29 managed without surgery. Overall, 81% presented with FIGO stage IVB-IVC disease. Complete cytoreduction was achieved in 89% of surgically treated patients. Median PFS was 34.2 months in the PDS group, 35.3 months in the IDS group, and 11.5 months in non-surgical patients. Median OS was not reached in the PDS group, 60 months in the IDS group, and 17.5 months in non-surgical patients. At multivariable analysis, both PDS (HR 0.20, p = 0.004) and IDS (HR 0.07, p < 0.001) were associated with improved PFS compared with non-surgical management, while p53-abnormal subtype emerged as the only independent adverse prognostic factor for PFS (HR 3.13, p = 0.014). CONCLUSIONS: A resectability-driven strategy achieved high complete cytoreduction rates and enabled selected IDS responders, initially unsuitable for PDS, to attain comparable survival outcomes, without establishing treatment equivalence. Molecular classification provided additional prognostic information and may further refine treatment selection in advanced EC.