INTRODUCTION

To evaluate BRCA1-2 (breast cancer) detection in men with high risk PCa, including the oncological consequences for the patient and family members.

MATERIALS AND METHODS

From January 2023 to December 2024, 52 men (median age 73 years;) with confirmed PCa diagnosis underwent somatic and germline BRCA1 and BRCA2 assessment; 11/52 (21%) patients documented a family history of cancer. Patients were at different clinical stages: high-grade (71% had a Gleason score ≥ 8), locally advanced (54% of cases) and/or metastatic PCa (46% of cases) at initial diagnosis, hormone-sensitive and/or castration-resistant PCa (38.2% of cases) at clinical progression. Formalin-fixed paraffin-embedded (FFPE) tissues and next generation sequencing (NGS) analyses of BRCA genes were evaluated on 52 samples (prostate biopsies or definitive samples) collected at Gravina Hospital (Caltagirone, Italy) from different Sicilian pathology departments. The therapeutic and clinical impact of genetic testing for BRCA somatic and germline mutations was evaluated for patients and their families.

RESULTS

All FFPE cases were successfully genotyped, with a good library and sequencing CQ metrics for all genes of interest; 10/52 (19.2%) patients had somatic or germline BRCA mutations, specifically, 3/52 (5.7%) had somatic and 7/52 (13.5%) had germline mutations. In the seven cases with germline variants, 4/7 (57%) had a family history of PCa or other diseases, while the remaining 3/7 (43%) patients had no hereditary predisposition. All identified genetic variants were related to the BRCA2 gene; after genetic screening of the corresponding relatives, various members of the analysed families carried the mutation identified in the proband, so that cancer prevention and/or active surveillance was possible.

CONCLUSIONS

NGS analysis for BRCA genetic testing using FFPE tissue in the clinical setting of patients with high-grade and/or metastatic PCa appears to be a valuable tool, not only for therapeutic purposes, but also to identify families with genetic predisposition who may be underdiagnosed according to canonical criteria.