A comprehensive real-world analysis has revealed significant gaps in both genetic testing practices and targeted therapy implementation for patients with metastatic castration-resistant prostate cancer (mCRPC), according to findings presented at the 2025 American Society of Clinical Oncology Genitourinary Cancers Symposium.
The study, which analyzed data from 1,022 mCRPC patients across 500 U.S. healthcare sites, found that only 63.6% of patients underwent homologous recombination repair gene mutation (HRRm) testing. More concerning, just 19% of patients received testing at the time of initial diagnosis, despite it being the standard of care for all mCRPC patients.
Testing Patterns and Timing
The analysis revealed a complex landscape of genetic testing implementation. Of those tested, 58.8% received somatic testing, while 21.2% underwent germline testing, and 3.4% had both. The timing of testing showed concerning delays, with 41% receiving testing during or after first-line treatment, and 22% during or after second-line treatment.
Mutation Profiles and Treatment Decisions
Among patients who tested positive for HRRm (38% of tested patients), the most common mutations were:
- BRCA2 (33.6%)
- ATM (30.9%)
- CHEK2 (13.2%)
- BRCA1 and CDK12 (6.6% each)
Despite the presence of actionable mutations, only 58.4% of HRRm-positive patients received PARP inhibitor therapy. Most concerning was the finding that 65% of patients who received PARP inhibitors started treatment after three or more lines of therapy, significantly later than optimal timing.
Treatment Gaps and Missed Opportunities
The study highlighted a particularly troubling trend where patients with established actionable mutations did not receive appropriate targeted therapy. Among patients who were not treated with PARP inhibitors, 15.9% carried BRCA2 mutations, 29% had ATM mutations, and 3.7% were BRCA1 positive – all of which are known to respond to PARP inhibitor therapy.
Clinical Practice Implications
"This extended real-world analysis confirms clinical practice gaps in the clinical management of mCRPC patients, demonstrating lack of or delayed biomarker testing and PARP inhibitor treatment," the researchers emphasized in their presentation. They stressed the need for continuing education and standardized testing practices to address these shortcomings.
The findings suggest a critical need for healthcare systems to implement more rigorous genetic testing protocols and establish clearer pathways for connecting positive test results to appropriate targeted therapies. The data also indicates that current guidelines for genetic testing and PARP inhibitor treatment in mCRPC may not be consistently followed in real-world clinical practice.
