An appraisal of genetic testing for prostate cancer susceptibility

Abstract Most criteria for genetic testing for prostate cancer susceptibility require a prior diagnosis of prostate cancer, in particular cases with metastatic disease are selected. Advances in the field are expected to improve outcomes through tailored treatments for men with advanced prostate cancer with germline pathogenic variants, although these are not currently offered in the curative setting. A better understanding of the value of genetic testing for prostate cancer susceptibility in screening, for early detection and prevention is necessary. We review and summarize the literature describing germline pathogenic variants in genes associated with increased prostate cancer risk and aggressivity. Important questions include: what is our ability to screen for and prevent prostate cancer in a man with a germline pathogenic variant and how does knowledge of a germline pathogenic variant influence treatment of men with nonmetastatic disease, with hormone-resistant disease and with metastatic disease? The frequency of germline pathogenic variants in prostate cancer is well described, according to personal and family history of cancer and by stage and grade of disease. The role of these genes in aggressive prostate cancer is also discussed. It is timely to consider whether or not genetic testing should be offered to all men with prostate cancer. The goals of testing are to facilitate screening for early cancers in unaffected high-risk men and to prevent advanced disease in men with cancer.