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

## TL;DR

This study finds that the timing of surgery for advanced ovarian cancer may depend on whether the tumor has BRCA mutations, with earlier surgery improving survival for BRCA-mutated patients.

## Contribution

The study identifies a survival benefit of primary surgery for BRCA-mutated ovarian cancer patients in the PARP inhibitor era.

## Key findings

- Overall survival was similar between primary and interval surgery in advanced ovarian cancer patients.
- BRCA-mutated patients had better survival when surgery was performed first.
- Surgical timing had little impact on outcomes in patients without BRCA mutations.

## Abstract

The best timing of surgery for advanced ovarian cancer remains unclear, especially since new drugs called PARP inhibitors have greatly improved patient outcomes. Traditionally, surgery is performed either before chemotherapy (primary surgery) or after initial chemotherapy (interval surgery), but it is unknown whether one approach is better in the modern treatment era. In this study, we examined patients with advanced high-grade serous ovarian cancer who were treated with current standard therapies, including PARP inhibitors. Overall survival was similar between the two surgical approaches when patient backgrounds were carefully adjusted. However, patients with tumors carrying BRCA mutations showed better survival when surgery was performed first. In contrast, surgical timing had little impact on outcomes in patients without BRCA mutations. These findings suggest that the optimal timing of surgery may depend on the biological features of the tumor. Incorporating genetic information such as BRCA status into surgical planning may help personalize treatment and improve outcomes for patients with advanced ovarian cancer.

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.