Multicenter Evaluation of [-2]Proprostate-Specific Antigen and the Prostate Health Index for Detecting Prostate Cancer

BACKGROUND: Total prostate-specific antigen (tPSA) is flawed for prostate cancer (PCa) detection. [-2]proprostate-specific antigen (p2PSA), a molecular isoform of free PSA (fPSA), shows higher specificity compared with tPSA or percentage of free PSA (%fPSA). The prostate health index (Phi), a measure based on p2PSA and calculated as p2PSA/fPSA X root tPSA, was evaluated in a multicenter study for detecting PCa. METHODS: A total of 1362 patients from 4 different study sites who had tPSA values of 1.6-8.0 if mu g/L (668 patients with PCa, 694 without PCa) underwent >= 10 core biopsies. Serum concentrations of tPSA, fPSA (both calibrated against a WHO reference material), and p2PSA were measured on Access2 or DxI800 analyzers (Beckman Coulter). RESULTS: The percentage ratio of p2PSA to fPSA (%p2PSA) and Phi were significantly higher in all PCa subcohorts (positive initial or repeat biopsy result or negative digital rectal examination) (P < 0.0001) compared with patients without PCa. Phi had the largest area under the ROC curve (AUC) (AUC = 0.74) and provided significantly better clinical performance for predicting PCa compared with %p2PSA (AUG = 0.72, P = 0.018), p2PSA (AUG = 0.63,P < 0.0001), %fPSA (AUC = 0.61) or tPSA (AUG = 0.56). Significantly higher median values of Phi were observed for patients with a Gleason score >= 7 (Phi = 60) compared with a Gleason score <7 (Phi = 53; P = 0.0018). The proportion of aggressive PCa (Gleason score >= 7) increased with the Phi score. CONCLUSIONS: The results of this multicenter study show that Phi, compared with tPSA or %fPSA, demonstrated superior clinical performance in detecting PCa at tPSA 1.6-8.0 mu g/L (i.e., approximately 2-10 mu g/L in traditional calibration) and is better able to detect aggressive PCa. (C) 2012 American Association for Clinical Chemistry