The Prostate Health Index Selectively Identifies Clinically Significant Prostate Cancer

PURPOSE: The Prostate Health Index (phi) is a new test combining total, free and -2proPSA into a single score. It was recently approved by the FDA and is now commercially available in the U.S., Europe and Australia. We investigate whether phi improves specificity for detecting clinically significant prostate cancer and can help reduce prostate cancer over diagnosis. MATERIALS AND METHODS: From a multicenter prospective trial we identified 658 men age 50 years or older with prostate specific antigen 4 to 10 ng/ml and normal digital rectal examination who underwent prostate biopsy. In this population we compared the performance of prostate specific antigen, % free prostate specific antigen, -2proPSA and phi to predict biopsy results and, specifically, the presence of clinically significant prostate cancer using multiple criteria. RESULTS: The Prostate Health Index was significantly higher in men with Gleason 7 or greater and "Epstein significant" cancer. On receiver operating characteristic analysis phi had the highest AUC for overall prostate cancer (AUCs phi 0.708, percent free prostate specific antigen 0.648, -2proPSA 0.550 and prostate specific antigen 0.516), Gleason 7 or greater (AUCs phi 0.707, percent free prostate specific antigen 0.661, -2proPSA 0.558, prostate specific antigen 0.551) and significant prostate cancer (AUCs phi 0.698, percent free prostate specific antigen 0.654, -2proPSA 0.550, prostate specific antigen 0.549). At the 90% sensitivity cut point for phi (a score less than 28.6) 30.1% of patients could have been spared an unnecessary biopsy for benign disease or insignificant prostate cancer compared to 21.7% using percent free prostate specific antigen. CONCLUSIONS: The new phi test outperforms its individual components of total, free and -2proPSA for the identification of clinically significant prostate cancer. Phi may be useful as part of a multivariable approach to reduce prostate biopsies and over diagnosis.