PD-L1 expression in prostate cancer and Gleason Grade Group: Is there any relationship? Findings from a multi-institutional cohort

BACKGROUND: PD-L1 expression in prostate cancer (PCa) is a complex phenomenon, and its clinical utility is debated. While it is a potential target for immunotherapy, interpreting PD-L1 scores remains unstandardized, and its role in guiding treatment decisions is unclear. Our study aimed to investigate the relationship between PD-L1 expression (measured by Combined Positive Score, CPS) and PCa aggressiveness (indicated by Gleason Grade Groups [GGs]). MATERIALS AND METHODS: A retrospective analysis of 120 prostate biopsies from 52 PCa patients was conducted. PD-L1 CPS was assessed and the correlation between CPS and GGs was statistically analyzed. RESULTS: A non-linear correlation was observed between CPS positivity and increasing GG, with the highest proportion in GG2 and GG5. Notably, GG5 exhibited the highest PD- L1 expression. However, PD-L1 expression varied within patients, indicating heterogeneity. Despite the non-linear correlation, statistical analyses confirmed a positive association overall, with higher GGs generally showing increased CPS values. A one-way ANOVA demonstrated a statistically significant difference in mean CPS values across the different GGs (p < 0.0001) and linear regression analysis further confirmed a direct correlation between PD-L1 values and GG (p < 0.0001). A significant association was also observed between cribriform morphology and CPS ≥ 1. Additionally, patients with CPS ≥ 1 had a shorter biochemical recurrence (BCR)-free survival. CONCLUSIONS: Our study highlights a positive correlation between PD-L1 expression and GG in PCa, suggesting that higher PD-L1 expression is linked to more aggressive disease. This finding could have implications for treatment selection and the use of immunotherapy, particularly for patients with higher GGs.