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 (Ra) 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 Ra, 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 Ra 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 Ra 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 Ra treatment, but prospective validation is required.