Homologous Recombination Repair Mutations, Next-generation Sequencing Testing, and Treatment Progression by Race
Mehmet A Bilen1, Neal Shore2, Sabree Burbage3
1Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, GA.
Urology
|January 31, 2026
Summary
Next-generation sequencing (NGS) testing for homologous recombination repair (HRR) mutations in metastatic castration-sensitive prostate cancer (mCSPC) has increased but remains insufficient. Most patients experience disease progression within 24 months, highlighting a critical need for improved testing rates across all racial groups.
Area of Science:
- Oncology
- Genetics
- Clinical Trials
Background:
- Metastatic castration-sensitive prostate cancer (mCSPC) management benefits from understanding homologous recombination repair (HRR) mutations.
- Next-generation sequencing (NGS) is crucial for identifying HRR alterations.
- Disparities in genomic testing may impact treatment decisions and outcomes.
Purpose of the Study:
- To evaluate NGS testing rates for deleterious HRR mutations in US patients with mCSPC.
- To assess the time-to-next-treatment (TTNT) based on HRR mutation testing status.
- To analyze testing patterns and TTNT across different racial subgroups.
Main Methods:
- Retrospective analysis of the Flatiron Health-Foundation Medicine, Inc. Clinico-Genomic Database and Core Registry (2018-2023).
- Inclusion of patients with mCSPC who initiated treatment after January 1, 2018, and underwent HRR testing.
- Kaplan-Meier analysis for TTNT and descriptive statistics for NGS testing rates by race.
Main Results:
- Among 1,121 HRR-tested mCSPC patients, 15.2%-17.4% harbored HRR alterations (BRCA1/2).
- Non-White patients showed the shortest median TTNT (17.0 months), followed by White (19.2 months) and Black patients (21.2 months).
- NGS testing rates increased overall and became comparable across racial groups by 2023, despite initial disparities.
Conclusions:
- NGS testing rates for mCSPC patients have improved but remain unacceptably low.
- Significant proportions of patients progress to next treatment within 24 months, irrespective of race.
- Addressing disparities and increasing overall NGS testing are critical for optimal mCSPC care.
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