title: Preoperative prostate-specific antigen isoform p2PSA ≤ 22.5 pg/ml predicts advanced prostate cancer in patients undergoing radical prostatectomy.
abstract: BACKGROUND
  The prediction value of prostate-specific antigen (PSA) isoform [-2]proPSA (p2PSA) for detecting advanced prostate cancer (PCa) remains unclear. Our objective was to evaluate the additional clinical utility of p2PSA compared with total PSA (tPSA), free PSA (fPSA), and preoperative Gleason score (Gls) in predicting locally advanced PCa (pT3/T4) with high-accuracy discrimination. The aim was to develop a novel classification based on p2PSA and preoperative Gls for predicting advanced PCa.
  
  
  METHODS
  In 208 consecutive men diagnosed with clinically localized PCa who underwent radical prostatectomy, we determined the predictive and discriminatory accuracy of serum tPSA, fPSA, percentage of fPSA to tPSA, p2PSA, p2PSA density, percentage of p2PSA to fPSA, and the Prostate Health Index. The cutoff level of p2PSA with best accuracy was estimated. The novel classification was developed by analyzing the interaction between p2PSA and Gls in predicting pathologic outcomes using a chi-square automatic interaction detection analysis. Decision curve analysis was applied to test the clinical consequences of using the novel classification.
  
  
  RESULTS
  On univariate analyses, p2PSA, p2PSA density, percentage of p2PSA to fPSA, and Prostate Health Index were accurate but were not independent predictors by multivariate analysis. The p2PSA cutoff level of 22.5 pg/ml showed the best accuracy level for predicting and discriminating advanced diseases (area under the curve [AUC] = 0.725, sensitivity = 51.4%, specificity = 81.8%). By chi-square automatic interaction detection, univariate and multivariate analysis, a p2PSA level > 22.5 pg/ml was significantly associated with an increased frequency and risk of advanced disease. In patients with a p2PSA level ≤ 22.5 pg/ml, 91.8% of Gleason sum 6 PCa was organ confined. The combination of p2PSA and Gls enhanced slightly but significantly the predictive and discriminatory accuracy for advanced disease (0.6%-3.6%).
  
  
  CONCLUSIONS
  The p2PSA cutoff level of 22.5 pg/ml can accurately discriminate between organ-confined and advanced PCa. The additional use of p2PSA enhanced slightly the predictive accuracy for advanced PCa (pT3/pT4) and has limited additional predictive value in identifying aggressive PCa (Gls > 7a).
authors.affiliation: Department of Urology, University Hospital of Cologne, Cologne, Germany. Electronic address: okyaz.eminaga@uk-koeln.de.
authors.forename: Okyaz
authors.initials: O
authors.lastname: Eminaga
authors.affiliation: Prostate Center, Department of Urology, University Hospital Muenster, Albert-Schweitzer-Campus 1, Muenster, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Bögemann
authors.affiliation: Department of Medical Informatics, University Muenster, Muenster, Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Breil
authors.affiliation: Prostate Center, Gerhard-Domagk Institute for Pathology, University Hospital Muenster, Muenster, Germany.
authors.forename: Ulf
authors.initials: U
authors.lastname: Titze
authors.affiliation: Prostate Center, Gerhard-Domagk Institute for Pathology, University Hospital Muenster, Muenster, Germany.
authors.forename: Fabian
authors.initials: F
authors.lastname: Wötzel
authors.affiliation: Institute of Pathology, Saarbrücken-Rastpfuhl, Saarbrücken, Germany.
authors.forename: Elke
authors.initials: E
authors.lastname: Eltze
authors.affiliation: Institute of Pathology and Cytology, Schüttorf, Germany.
authors.forename: Olaf
authors.initials: O
authors.lastname: Bettendorf
authors.affiliation: Prostate Center, Department of Urology, University Hospital Muenster, Albert-Schweitzer-Campus 1, Muenster, Germany.
authors.forename: Axel
authors.initials: A
authors.lastname: Semjonow
mesh_terms: D000328:Adult; D000368:Aged; D006801:Humans; D007610:Kallikreins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D057234:Preoperative Period; D011379:Prognosis; D017430:Prostate-Specific Antigen / Q000097:blood*; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000097:blood* / Q000473:pathology / Q000601:surgery; D020033:Protein Isoforms
chemical_list: D020033:Protein Isoforms; C549870:KLK3 protein, human; D007610:Kallikreins; D017430:Prostate-Specific Antigen
keywords: Discrimination; Predictive tools; ProPSA; Prostate cancer; [−2]proPSA; cMDX; p2PSA; p2PSA threshold level 22.5pg/ml