Prognostic value of PD-L1 expression and association with HRD in high-grade serous ovarian cancer: an ancillary analysis of the PAOLA-1/ENGOT-ov25 trial (GINECO).
Abstract
Background
The prognostic significance of programmed death-ligand 1 (PD-L1) in high-grade serous ovarian cancer (HGSOC) remains uncertain, because of heterogeneity in assays, scoring systems, and assessment of tumor and immune compartments across studies. We therefore evaluated its biological and prognostic relevance using a standardized pathological approach in a large, well-annotated phase III trial cohort.
Materials And Methods
In this ancillary retrospective biomarker analysis of PAOLA-1/ENGOT-ov25, PD-L1 was assessed by 22C3 pharmDx immunohistochemistry on whole-slide sections from 324 International Federation of Gynecology and Obstetrics stage III-IV HGSOCs. Three predefined scoring systems commonly used in PD-L1 assessment were applied: tumor proportion score (TPS ≥1%), immune cell score (IC ≥1%), and combined positive score (CPS ≥1). Associations with homologous recombination deficiency (HRD), BRCA1/2 status, and survival were examined using multivariable Cox models adjusted for major clinicopathological factors.
Results
PD-L1 positivity was observed in 38.2% of tumors by TPS, 62.4% by IC, and 66.1% by CPS. Positivity did not significantly vary by sampling site or timing of tissue collection relative to chemotherapy. PD-L1 positivity was enriched in HRD-positive tumors (TPS: 42.3% versus 28.0%, P = 0.017; IC: 65.1% versus 52.0%, P = 0.030; CPS: 70.4% versus 53.0%, P = 0.003) and remained independently associated with improved overall survival in adjusted analyses [TPS: adjusted hazard ratio (aHR) 0.70 (95% confidence interval 0.49-1.00), P = 0.046; IC: aHR 0.68 (0.49-0.95), P = 0.025; CPS: aHR 0.70 (0.50-0.97), P = 0.037]. Associations with progression-free survival were not statistically significant after adjustment.
Conclusions
In advanced HGSOC, standardized whole-slide PD-L1 assessment identifies an HRD-associated PD-L1-positive immune context independently associated with improved overall survival. Immune-integrated scoring approaches capture this signal more effectively than tumor-cell-restricted assessment and provide a robust framework for future ovarian cancer studies.