Metastatic castration-resistant prostate cancer (mCRPC) is a heterogeneous disease in which molecular stratification is needed to improve clinical outcomes. The identification of predictive biomarkers can have a major impact on the care of these patients, but the availability of metastatic tissue samples for research in this setting is limited.
To study the prevalence of immune biomarkers of potential clinical utility to immunotherapy in mCRPC and to determine their association with overall survival (OS).
From 100 patients, mCRPC biopsies were assayed by whole exome sequencing, targeted next-generation sequencing, RNA sequencing, tumor mutational burden, T-cell-inflamed gene expression profile (TcellinfGEP) score (Nanostring), and immunohistochemistry for programmed cell death 1 ligand 1 (PD-L1), ataxia-telangiectasia mutated (ATM), phosphatase and tensin homolog (PTEN), SRY homology box 2 (SOX2), and the presence of neuroendocrine features.
The phi coefficient determined correlations between biomarkers of interest. OS was assessed using Kaplan-Meier curves and adjusted hazard ratios (aHRs) from Cox regression.
PD-L1 and SOX2 protein expression was detected by immunohistochemistry (combined positive score ≥1 and >5% cells, respectively) in 24 (33%) and 27 (27%) mCRPC biopsies, respectively; 23 (26%) mCRPC biopsies had high TcellinfGEP scores (>-0.318). PD-L1 protein expression and TcellinfGEP scores were positively correlated (phi 0.63 [0.45; 0.76]). PD-L1 protein expression (aHR: 1.90 [1.05; 3.45]), high TcellinfGEP score (aHR: 1.86 [1.04; 3.31]), and SOX2 expression (aHR: 2.09 [1.20; 3.64]) were associated with worse OS.
PD-L1, TcellinfGEP score, and SOX2 are prognostic of outcome from the mCRPC setting. If validated, predictive biomarker studies incorporating survival endpoints need to take these findings into consideration.
This study presents an analysis of immune biomarkers in biopsies from patients with metastatic prostate cancer. We describe tumor alterations that predict prognosis that can impact future studies.
European urology oncology. 2022 Apr 28 [Epub ahead of print]
María Dolores Fenor de la Maza, Khobe Chandran, Jan Rekowski, Irene M Shui, Bora Gurel, Emily Cross, Suzanne Carreira, Wei Yuan, Daniel Westaby, Susana Miranda, Ana Ferreira, George Seed, Mateus Crespo, Ines Figueiredo, Claudia Bertan, Veronica Gil, Ruth Riisnaes, Adam Sharp, Daniel Nava Rodrigues, Pasquale Rescigno, Nina Tunariu, Xiao Qiao Liu, Razvan Cristescu, Charles Schloss, Christina Yap, Johann S de Bono
The Institute of Cancer Research, London, UK; The Royal Marsden Hospital, London, UK., The Institute of Cancer Research, London, UK., Merck & Co., Inc., Kenilworth, NJ, USA., Royal Free Hospital, London, UK., Candiolo Cancer Institute, FPO-IRCCS, Candiolo, Turin, Italy., The Institute of Cancer Research, London, UK; The Royal Marsden Hospital, London, UK. Electronic address: .