A recent study presented at the ASCO GU 2025 Annual Meeting examined the influence of homologous recombination repair alterations (HRRalt) on survival outcomes in patients with metastatic hormone-sensitive prostate cancer (mHSPC).

The research utilized data from the Flatiron Health-Foundation Medicine prostate cancer clinico-genomic database, encompassing approximately 280 U.S. cancer clinics.
The retrospective study included 637 patients diagnosed with de novo mHSPC who underwent tissue biopsy within 90 days of diagnosis and initiated androgen deprivation therapy intensification (ADTi) with either an androgen receptor pathway inhibitor (ARPI) or a taxane within 120 days of diagnosis. Among these patients, 181 (28.4%) exhibited HRR alterations in 14 pre-specified genes.

Time to Castration Resistance (TTCR): Patients with HRR alterations experienced a significantly shorter TTCR compared to those with wild-type HRR. Specifically, the adjusted hazard ratio (aHR) for TTCR was 1.5 (95% CI: 1.1–2.0) in patients receiving ADT plus ARPI, and 1.7 (95% CI: 1.2–2.3) in those receiving ADT plus taxane.
No significant differences in overall survival were observed between patients with HRR alterations and those with wild-type HRR.

Specifically, since BRCA, ATM and CDK12 are specifically discussed in the source text, the finding are as follows:

If you have an ATM mutation, your treatment approach won’t change significantly, as your outcomes are similar to those without the mutation. Both time to castration resistance (TTCR) and overall survival (OS) show no major differences compared to non-ATM-mutated patients.

If you have a BRCA1/2 mutation, your cancer may progress to castration resistance faster (shorter TTCR), meaning you might need additional treatments sooner. However, overall survival (OS) remains similar to that of patients without BRCA mutations.

If you have a CDK12 mutation, your cancer is far more aggressive, with both TTCR and OS significantly worse compared to non-mutated patients. This suggests a higher risk of early treatment resistance and shorter survival, requiring a more proactive treatment approach.

Source.