DNA damage repair gene defects combined predict the efficacy of immune checkpoint inhibitors in metastatic castration-resistant prostate cancer: a retrospective cohort study.

Combined DDR gene mutation profiling with TMB and PD-L1 predicts immunotherapy response in 152 metastatic castration-resistant prostate cancer patients, with an AUC of 0.83.

• Why it matters: Heterogeneous responses to immune checkpoint inhibitors in mCRPC highlight the need for reliable biomarkers to identify patients who will benefit from therapy, improving personalized treatment strategies.
• What they did: Researchers conducted a retrospective study of 152 patients, analyzing DDR gene mutations, TMB, and PD-L1 expression through targeted NGS panels, and assessed their predictive value for treatment outcomes.
• The result: The integrated biomarker panel accurately stratified patients, with DDR mutations, high TMB, and PD-L1 expression independently predicting longer PFS, supporting its potential for guiding immunotherapy decisions.