Survival outcomes for men with metastatic castration-resistant prostate cancer (mCRPC) with and without homologous recombination deficiencies (HRD) treated with radium 223: Princess Margaret Cancer Centre (PMCC) experience.

Background: Radium-223 (²²³Ra) targets bone metastases in metastatic castration resistant prostate cancer (mCRPC) and induces double-strand DNA breaks. We hypothesized that patients with homologous recombination deficiencies (HRD) may exhibit heightened sensitivity to ²²³Ra, resulting in improved survival outcomes.

Methods: This retrospective analysis was performed in men with mCRPC and bone metastases, with and without HRD, treated with androgen deprivation therapy (ADT) and ²²³Ra at the PMCC. Demographics, disease characteristics, and/or somatic DNA sequencing data were collected.

Results: Between 2015 and 2022, we identified 40 mCRPC patients who underwent ²²³Ra therapy and had germline and/or somatic DNA sequencing data available. HRD mutations were found in 9/40 (22.5%) patients. Median overall survival was longer in the HRD group vs. non-HRD group (24 vs 12 months; p = 0.038). Median progression-free survival was 5.7 vs. 3.3 months (P = 0.74). PSA response was also higher in the HRD group (33.3% vs. 9.7%; P = 0.11), as was ALP response (66.7% vs. 58.1%; p = 0.72). Among patients with an ALP response, 3-year survival probability was 33% in the HRD group vs 11% in the non-HRD group (P = 0.03).

Conclusions: Despite the small size, these findings suggest that patient with HRD may have a slight improvement in survival outcomes after ²²³Ra treatment, but prospective validation is required.