title: Evaluation of prostate-specific antigen isoform p2PSA and its derivates, %p2PSA, prostate health index and prostate dimension-adjusted related index in the detection of prostate cancer at first biopsy: an exploratory, prospective study.
abstract: OBJECTIVE
  To confirm the accuracy of serum proPSA (p2PSA) and its derivatives, percentage of p2PSA to free PSA (%p2PSA) and Prostate Health Index (PHI) and to test the value of prostate dimension-adjusted related index p2PSA density (p2PSAD), %p2PSA density (%p2PSAD) and PHI density (PHID) in discriminating between patients with and without prostate cancer (PCa).
  
  
  METHODS
  This is a prospective cohort study of 275 patients with a total PSA (tPSA) of 2-10 ng/ml who underwent initial prostate biopsy. Multivariate logistic regression models were complemented by predictive accuracy analysis.
  
  
  RESULTS
  PCa was diagnosed in 31.2% of subjects. Median tPSA did not differ between groups, while PSA density (PSAD), percent free PSA (%fPSA), p2PSA, %p2PSA, PHI, p2PSAD, %p2PSAD and PHID (all p < 0.05) were different between men with and without PCa. Univariate accuracy analysis showed p2PSAD (area under the receiver-operating characteristic curve [AUC]: 0.71), %p2PSAD (AUC: 0.76) and PHID (AUC: 0.77) to be the most accurate predictors of PCa at biopsy, significantly outperforming tPSA (AUC: 0.54), PSAD (AUC: 0.68) and %fPSA (AUC: 0.59) (p ≤ 0.001). At multivariate logistic regression models, p2PSAD and PHID signiﬁcantly increased the accuracy of the basal multivariate model (all p < 0.01). At 90% specificity, sensitivity for p2PSAD, %p2PSAD and PHID were 33.7, 43 and 40.7%, respectively. Spearman's rho coefficient analysis demonstrated a significant relationship between Gleason score, %p2PSA (r = 0.216, p = 0.046), PHI (r = 0.223, p = 0.039) and %p2PSAD (r = 0.205, p = 0.05).
  
  
  CONCLUSIONS
  Considering patients suited for initial prostate biopsy by a tPSA range of 2-10 ng/ml, PSA isoforms were confirmed to be strong predictors of PCa. The prostate dimension-adjusted PSA isoforms have been shown to differentiate between patients with or without PCa, with an AUC of 0.71-0.77, p2PSAD offering a gain in accuracy with respect to tPSA, %fPSA and PSAD.
authors.affiliation: Department of Urology, University of Perugia, Perugia, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Mearini
authors.forename: Carla
authors.initials: C
authors.lastname: Ferri
authors.forename: Massimo
authors.initials: M
authors.lastname: Lazzeri
authors.forename: Vittorio
authors.initials: V
authors.lastname: Bini
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Nunzi
authors.forename: Doriana
authors.initials: D
authors.lastname: Fiorini
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Costantini
authors.forename: Gianluca Carlo
authors.initials: GC
authors.lastname: Manasse
authors.forename: Massimo
authors.initials: M
authors.lastname: Porena
mesh_terms: D000368:Aged; D019540:Area Under Curve; D001706:Biopsy; D016009:Chi-Square Distribution; D006304:Health Status; D006305:Health Status Indicators; D006801:Humans; D007118:Immunoassay; D007610:Kallikreins / Q000097:blood*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000097:blood* / Q000000981:diagnostic imaging / Q000473:pathology*; D020033:Protein Isoforms; D012372:ROC Curve; D014463:Ultrasonography
chemical_list: D020033:Protein Isoforms; C549870:KLK3 protein, human; D007610:Kallikreins; D017430:Prostate-Specific Antigen