title: Multicenter evaluation of [-2]proprostate-specific antigen and the prostate health index for detecting prostate cancer.
abstract: 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 × √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 μg/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 (AUC = 0.72, P = 0.018), p2PSA (AUC = 0.63, P < 0.0001), %fPSA (AUC = 0.61) or tPSA (AUC = 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 μg/L (i.e., approximately 2-10 μg/L in traditional calibration) and is better able to detect aggressive PCa.
authors.affiliation: Department of Urology, Charité-Universitätsmedizin Berlin, Berlin, Germany. carsten.stephan@charite.de
authors.forename: Carsten
authors.initials: C
authors.lastname: Stephan
authors.forename: Sébastien
authors.initials: S
authors.lastname: Vincendeau
authors.forename: Alain
authors.initials: A
authors.lastname: Houlgatte
authors.forename: Henning
authors.initials: H
authors.lastname: Cammann
authors.forename: Klaus
authors.initials: K
authors.lastname: Jung
authors.forename: Axel
authors.initials: A
authors.lastname: Semjonow
mesh_terms: D001706:Biopsy; D016022:Case-Control Studies; D006801:Humans; D008297:Male; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000473:pathology; D012372:ROC Curve; D012680:Sensitivity and Specificity
chemical_list: D017430:Prostate-Specific Antigen