Homologous recombination repair genetic testing variables and diagnostic paths for prostate cancer patients: a multicenter cohort study.

BACKGROUND: Evidence on homologous recombination repair (HRR) mutation prevalence in prostate cancer (PC) patients and the diagnostic testing path to guide treatment remains limited outside of clinical trials. The objective of this study was to investigate the DNA source, type of tumor tissue, timing for testing in the patient's disease course, and rate of conclusive results in a real-world population.

PATIENTS AND METHODS: This was an observational, cohort study, involving 20 Italian cancer centers. The study population included consecutive PC patients undergoing germline, tumor, and/or plasma circulating tumor DNA (ctDNA) to profile HRR genes between January 1, 2020 and January 31, 2025.

RESULTS: Among 1400 PC patients included, 248 (17.7%) showed (likely)pathogenic variants (PVs) in the HRR genes. Most HRR testing was conducted during the metastatic castration-resistant PC (mCRPC)(779, 62.8%). The rate of conclusive results was 89.7% and varied widely according to the type of tumor tissue. The prevalence of HRR alterations was 18.1% in the mCRPC and 13.8% in the hormone-sensitive PC (P = .06). The concordance between tumor testing and ctDNA was 83.9%. Interestingly, 4.6% reported ctDNA testing positive but tumor testing negative, leading to important therapeutic implications. The prevalence of positive ctDNA testing was 47.4% vs 10.5%, for testing within 1 month or over 3 months, respectively, from the initiation of a new line of therapy.

CONCLUSION: This large real-world study, through the workflow adopted by clinicians for HRR genomic testing, provides novel insights into the variables influencing the success rate of genomic testing.