Real-world insights from comprehensive genomic profiling in patients with metastatic castration-resistant prostate cancer.

[INTRODUCTION] Comprehensive genomic profiling (CGP) has expanded treatment options for metastatic castration-resistant prostate cancer (mCRPC); however, real-world data on its clinical utility in Japanese patients remain limited. To address this gap, we conducted a multicenter real-world analysis to evaluate the implementation and clinical relevance of CGP in Japanese patients with mCRPC.

[METHODS] We retrospectively analyzed 128 patients with mCRPC who underwent CGP at four Japanese institutions using FoundationOne® CDx, FoundationOne® Liquid CDx, or OncoGuide™ NCC Oncopanel. We assessed the prevalence of druggable genomic signatures, including BRCA pathogenic variants (PVs), microsatellite instability-high (MSI-high), and tumor mutational burden-high (TMB-high), and described subsequent use of genomically matched therapies.

[RESULTS] The median age at CGP testing was 73 years, and patients had received a median of three prior systemic treatment lines. BRCA PVs were identified in 18 patients (14%), MSI-high in 4 (3%), and TMB-high in 11 (9%); all MSI-high cases were also TMB-high. Overall, 26 patients (20%) harbored either BRCA PVs or TMB-high status. Among these, 14 patients (54%) received matched targeted therapies, including poly(ADP-ribose) polymerase inhibitors or pembrolizumab. BRCA PVs were detected in 17% of tissue-based (F1 CDx) assays and 9% of liquid-based assays, without a statistically significant difference.

[CONCLUSIONS] CGP identified BRCA PVs, MSI-high, or TMB-high in 20% of patients with metastatic CRPC, supporting its value in guiding precision oncology. However, only some patients received matched therapy, supporting earlier CGP testing. Routine integration of CGP may facilitate precision oncology-guided treatment decision-making in this population.