Practical tricks and recommendations on BRCA1/2 testing in prostate cancer: From therapy to cancer prevention

Prostate cancer (PC) is the most frequently diagnosed cancer among men in the Western World. When it is diagnosed and treated at localized stages, it has a 97 % 5-yr cancer-specific survival compared to 30 % in the metastatic setting. Recently, inhibitors of the Poly(ADP-ribose) polymerase (PARPi) were shown to be effective treatments for metastatic PC harbouring defects in the homologous recombination mechanism of DNA repair (HRR), mainly in the BRCA1/2 genes. The BRCA1/2 pathogenetic variants are currently used, in clinical setting, as predictive markers for PARP-i therapy eligibility in patients with metastatic castration-resistant PC (mCRPC). BRCA1/2 pathogenetic variants are also responsible for inherited cancer predisposition syndromes when they are detected in the germinal setting. For this reason, it is of paramount importance that germline genetic testing be triggered following the identification of BRCA somatic variants in order to implement appropriate prevention pathways for subjects with high cancer risk. To date, there are no standardised protocols for this dual path of personalized therapy and prevention through the identification of subjects at high risk of cancer. AIFET and SIURO in this paper analyse the critical points of this dual path and propose a working model.