Specific HRR Gene Alterations Linked to Outcomes After Lu-PSMA-617

A retrospective genomic study of 205 patients with metastatic castration-resistant prostate cancer treated with Lu-PSMA-617 at the University of Minnesota (2022-2026) examined whether individual homologous recombination repair (HRR) gene alterations, rather than composite HRR status, predicted treatment outcomes. The study reported that one gene alteration (present in 12.7% of patients) was independently associated with improved PSA response, longer progression-free survival, and longer overall survival, while another alteration was associated with significantly worse PFS and OS; a pooled analysis of published studies corroborated these associations with overall survival. The authors state that marked heterogeneity among individual HRR genes supports gene-level rather than composite HRR analysis for precision oncology in radiopharmaceutical therapy.

Most relevant for: Patients with metastatic castration-resistant prostate cancer being considered for or undergoing Lu-PSMA-617 radioligand therapy.

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