Ovarian Cancer in the Era of Precision Surgery and Targeted Therapies

High-grade serous ovarian cancer (HGSC) is the most common and aggressive subtype of ovarian cancer. Despite initial response to platinum-based chemotherapy, most patients relapse. Cytoreductive surgery at relapse has been shown to improve survival in selected patients, but the biological mechanisms underlying recurrence and resistance remain unclear. This study aimed to investigate whether the mutational profile of HGSC changes from diagnosis to relapse, and to evaluate treatment patterns and survival outcomes in a cohort undergoing cytoreductive surgery.

Sixteen patients with HGSC who underwent cytoreductive surgery at both diagnosis and relapse were included. Matched tumor tissue samples (n = 32) were collected and sequenced using a 501-gene cancer panel. Only pathogenic or likely pathogenic variants were registered. Clinical data, treatment history, and survival outcomes were obtained from medical records, with a median follow-up of 63 months.

All patients harbored pathogenic or likely pathogenic mutations, most frequently in TP53 (88%) and BRCA1/2 (38%). The mutational landscape was largely stable, with 15 of 16 patients (94%) showing no mutational changes between diagnosis and relapse. One patient acquired a NOTCH2 mutation at relapse. Complete resection was achieved in 88% of relapse surgeries. Median time to first relapse was 32 months, and overall survival was prolonged, with 87.5% of patients alive at last follow-up. BRCA mutated patients showed longer time to relapse, and overall follow-up compared to BRCA wild-type cases.

The somatic mutational profile of HGSC remains remarkably stable from diagnosis to relapse. Clinically, this stability suggests that repeat mutational sequencing at relapse is unlikely to yield new actionable findings and may have limited value in guiding treatment decisions. Instead, resistance mechanisms likely arise from epigenetic or non-genetic changes, underscoring the need for future research in these areas and the continued importance of optimal surgical management in selected patients.