(UroToday.com) Next-generation sequencing has increasingly been incorporated into the standard of clinical care for advanced prostate cancer. The most widely-acknowledged use is in the evaluation of genomic alterations in the genes controlling homologous recombination (HR), the apparatus for repairing double-stranded DNA breaks. Two FDA-approved agents (olaparib, rucaparib) exist for patients with tumors deficient in HR, both of which are poly ADP-ribose polymerase inhibitors. Between these, the Phase 3 PROfound study demonstrated that treatment with olaparib significantly improved radiographic progression-free survival (versus physician’s choice of abiraterone or enzalutamide) in men with metastatic castration-resistant prostate cancer (mCRPC) and alterations in at least one of a subset of 15 genes involved in HR1. The authors note that 31% of potential subjects had a failure of molecular screening, underscoring that available tissue is crucial for both entry into a molecularly-qualified trial as well as making real-world clinical decisions. Dr. Chi et al. sought to evaluate the reliability of using plasma-based assays to detect deleterious mutations in BRCA1, BRCA1, and ATM (the gene alterations in Cohort A of PROfound).