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Lookup NU author(s): Dr Dan Westaby, Dr Pasquale RescignoORCiD
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).
Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.BACKGROUND: 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. OBJECTIVE: To study the prevalence of immune biomarkers of potential clinical utility to immunotherapy in mCRPC and to determine their association with overall survival (OS). DESIGN, SETTING, AND PARTICIPANTS: 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. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The phi coefficient determined correlations between biomarkers of interest. OS was assessed using Kaplan-Meier curves and adjusted hazard ratios (aHRs) from Cox regression. RESULTS AND LIMITATIONS: 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. CONCLUSIONS: 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. PATIENT SUMMARY: 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.
Author(s): Fenor de la Maza MD, Chandran K, Rekowski J, Shui IM, Gurel B, Cross E, Carreira S, Yuan W, Westaby D, Miranda S, Ferreira A, Seed G, Crespo M, Figueiredo I, Bertan C, Gil V, Riisnaes R, Sharp A, Rodrigues DN, Rescigno P, Tunariu N, Liu XQ, Cristescu R, Schloss C, Yap C, de Bono JS
Publication type: Article
Publication status: Published
Journal: European Urology Oncology
Year: 2022
Volume: 5
Issue: 6
Pages: 659-667
Print publication date: 01/12/2022
Online publication date: 28/04/2022
Acceptance date: 13/04/2022
Date deposited: 08/11/2024
ISSN (electronic): 2588-9311
Publisher: Elsevier BV
URL: https://doi.org/10.1016/j.euo.2022.04.004
DOI: 10.1016/j.euo.2022.04.004
PubMed id: 35491356
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