PD-L1 expression in prostate cancer and Gleason Grade Group: Is there any relationship? Findings from a multi-institutional cohort.
Vincenzo Fiorentino, Ludovica Pepe, Cristina Pizzimenti, Valeria Zuccalà, Pietro Pepe, Vincenzo Cianci, Cristina Mondello, Giovanni Tuccari, Guido Fadda, Giuseppe Giuffrè, Emanuela Germanà, Francesco Pierconti, Antonio Ieni, Maurizio Martini
Abstract
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.