The comprehensive analysis of 339 men found that the combination of prostate-specific antigen density (PSAD) and the Prostate Imaging Reporting and Data System (PI-RADS) improves the performance of the PI-RADS protocol in prostate cancer diagnosis in biopsy-naïve patients and can help in the risk decision-making process before prostate biopsy. This evidence concerns the gene KLK3 and Familial prostate cancer.