All this being considered, our preliminary data suggested that the presence of high-risk prostate cancer mutations (regarding ATM, BRCA1, and BRCA2 genes) might be the starting point for identifying a subset of patients who may benefit from systemic treatment and local radiotherapy in combination strategies since the first clinical and radiological evidence of metastatic, castrate-sensitive PC. This evidence concerns the gene BRCA1 and pachyonychia congenita.