title: Prostate-specific antigen (PSA) isoform p2PSA significantly improves the prediction of prostate cancer at initial extended prostate biopsies in patients with total PSA between 2.0 and 10 ng/ml: results of a prospective study in a clinical setting.
abstract: BACKGROUND
  Total prostate-specific antigen (tPSA), ratio of free PSA (fPSA) to tPSA (%fPSA), and PSA density (PSAD) testing have a very low accuracy in the detection of prostate cancer (PCa). There is an urgent need for more accurate biomarkers.
  
  
  OBJECTIVE
  To compare the diagnostic accuracy of PSA isoform p2PSA and its derivatives in determining the presence of PCa at initial biopsy with the accuracy of other predictors in patients with tPSA 2.0-10 ng/ml.
  
  
  METHODS
  We conducted an observational prospective study in a real clinical setting of consecutive men with tPSA 2.0-10 ng/ml and negative digital rectal examination who were scheduled for prostate biopsy at a tertiary academic center.
  
  
  METHODS
  Outpatient transrectal ultrasound-guided prostate biopsies were performed according to a standardized institutional saturation scheme (18-22 cores).
  
  
  METHODS
  We determined the diagnostic accuracy of serum tPSA, %fPSA, PSAD, p2PSA, %p2PSA [(p2PSA/fPSA)×100] and the Beckman Coulter Prostate Health Index (phi; [p2PSA/fPSA×√tPSA]).
  
  
  CONCLUSIONS
  Overall, 107 of 268 patients (39.9%) were diagnosed with PCa at extended prostate biopsies. Statistically significant differences between patients with and without PCa were observed for age, prostate and transition zone volume, PSAD, %p2PSA, and phi (all p values<0.05). In univariate accuracy analysis, phi and %p2PSA were the most accurate predictors of PCa (area under the curve: 75.6% and 75.7%, respectively), followed by transition zone volume (66%), prostate volume (65%), patient age (63%), PSAD (61%), %fPSA (58%), and tPSA (53%). In multivariate accuracy analyses, both phi (+11%) and %p2PSA (+10%) significantly improved the accuracy of established predictors in determining the presence of PCa at biopsy (p<0.001). Although %p2PSA and phi were significantly associated with Gleason score (Spearman ρ: 0.303 and 0.387, respectively; p ≤ 0.002), they did not improve the prediction of Gleason score ≥7 PCa in multivariable accuracy analyses (p > 0.05).
  
  
  CONCLUSIONS
  In patients with a tPSA between 2.0 and 10 ng/ml, %p2PSA and phi are the strongest predictors of PCa at initial extended biopsies and are significantly more accurate than the currently used tests (tPSA, %fPSA, and PSAD) in determining the presence of PCa at biopsy.
authors.affiliation: Department of Urology, San Raffaele Turro, Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Guazzoni
authors.forename: Luciano
authors.initials: L
authors.lastname: Nava
authors.forename: Massimo
authors.initials: M
authors.lastname: Lazzeri
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Scattoni
authors.forename: Giovanni
authors.initials: G
authors.lastname: Lughezzani
authors.forename: Carmen
authors.initials: C
authors.lastname: Maccagnano
authors.forename: Fernanda
authors.initials: F
authors.lastname: Dorigatti
authors.forename: Ferruccio
authors.initials: F
authors.lastname: Ceriotti
authors.forename: Marina
authors.initials: M
authors.lastname: Pontillo
authors.forename: Vittorio
authors.initials: V
authors.lastname: Bini
authors.forename: Massimo
authors.initials: M
authors.lastname: Freschi
authors.forename: Francesco
authors.initials: F
authors.lastname: Montorsi
authors.forename: Patrizio
authors.initials: P
authors.lastname: Rigatti
mesh_terms: D000046:Academic Medical Centers; D000368:Aged; D001706:Biopsy; D006305:Health Status Indicators; D006801:Humans; D007558:Italy; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011379:Prognosis; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000276:immunology / Q000473:pathology; D012372:ROC Curve; D018570:Risk Assessment; D012307:Risk Factors; D018084:Ultrasonography, Interventional
chemical_list: D017430:Prostate-Specific Antigen