In a multicenter prospective trial, Loeb et al. reported that PHI outperformed its individual components of total, free, and [-2]proPSA for the identification of clinically significant prostate cancer (Gleason ≥ 7; AUCs phi 0.707, percent free prostate-specific antigen 0.661, [-2]proPSA 0.558, prostate specific antigen 0.551) [39]. This evidence concerns the gene KLK3 and Familial prostate cancer.