Comparison of whole genome sequencing with clinical targeted panel sequencing of metastatic prostate cancer: insights from real-world data

<title>Abstract</title> We evaluated the clinical utility of Target-Enhanced Whole Genome Sequencing (TE-WGS) in comparison with targeted panel sequencing (TPS) for identifying clinically relevant genomic alterations in advanced prostate cancer. We applied TE-WGS to tumor/normal paired samples from patients with advanced prostate cancer previously tested with TPS during routine care. We compared the sensitivity of TE-WGS in detecting variants reported by TPS and assessed its added value in uncovering additional targetable alterations. A total of 45 samples from patients with advanced prostate cancer were analyzed using TE-WGS, which demonstrated 96.3% sensitivity in detecting clinically relevant variants reported by matched TPS. Furthermore, TE-WGS identified an additional 430 variants (85.0%) with clinical impact that were not reported by TPS. Notably, TE-WGS revealed rearrangements in DNA repair genes such as BRCA1/2, RAD51B, NBN, and CDK12. Overall, additional targetable alterations were detected by TE-WGS in 46.7% of samples, including 35.6% with no actionable findings by TPS, underscoring the added clinical value of WGS-based profiling. Our study highlights TE-WGS as a valuable complement to TPS, revealing clinically relevant targets that support its consideration in the management of advanced prostate cancer.