Surgical Timing and Survival in Advanced High-Grade Serous Ovarian Cancer in the PARP Inhibitor Era

Background: The optimal timing of cytoreductive surgery for advanced high-grade serous carcinoma (HGSC) remains a critical unmet question in the modern era of platinum-based chemotherapy and PARP inhibitor (PARPi) maintenance. To address this gap, we compared outcomes following primary debulking surgery (PDS) versus interval debulking surgery (IDS) in a uniformly treated, contemporary cohort. Methods: Patients with FIGO stage IIIB-IVB HGSC treated between 2019 and 2023 were retrospectively analyzed. Baseline tumor burden was assessed using detailed radiologic and laparoscopic evaluations, including both presurgical and intraoperative assessments. Progression-free survival (PFS) and overall survival (OS) were examined using multivariable Cox proportional hazards models and reported as adjusted hazard ratios (aHRs). Subgroup analyses were rigorously conducted according to residual disease status and BRCA mutation status. Results: Among 221 patients (PDS, n = 60; IDS, n = 151), the median follow-up was 40 months. In the overall cohort, adjusted PFS and OS did not differ significantly between the PDS and IDS groups (PFS: aHR, 1.15; 95%CI, 0.67-1.98; OS: aHR, 1.24; 95%CI, 0.54-2.83). Outcomes were comparable among patients achieving R0 resection. Notably, BRCA-mutated patients demonstrated a substantial survival advantage with PDS (BRCA-mutated PFS: aHR, 3.34; 95%CI, 1.06-16.67; OS: aHR, 6.07; 95%CI, 2.13-∞), whereas BRCA wild-type patients showed no significant difference between surgical strategies. Conclusions: The findings suggest that BRCA-mutated patients may derive a survival benefit from PDS, whereas surgical timing had a limited impact on BRCA wild-type disease. This result underscores the importance of integrating molecular profiling, particularly BRCA mutation status, with surgical assessment to guide optimal and personalized treatment strategies in the PARPi era.