title: Serum isoform [-2]proPSA derivatives significantly improve prediction of prostate cancer at initial biopsy in a total PSA range of 2-10 ng/ml: a multicentric European study.
abstract: BACKGROUND
  Strategies to reduce prostate-specific antigen (PSA)-driven prostate cancer (PCa) overdiagnosis and overtreatment seem to be necessary.
  
  
  OBJECTIVE
  To test the accuracy of serum isoform [-2]proPSA (p2PSA) and its derivatives, percentage of p2PSA to free PSA (fPSA; %p2PSA) and the Prostate Health Index (PHI)-called index tests-in discriminating between patients with and without PCa.
  
  
  METHODS
  This was an observational, prospective cohort study of patients from five European urologic centers with a total PSA (tPSA) range of 2-10 ng/ml who were subjected to initial prostate biopsy for suspected PCa.
  
  
  METHODS
  The primary end point was to evaluate the specificity, sensitivity, and diagnostic accuracy of index tests in determining the presence of PCa at prostate biopsy in comparison to tPSA, fPSA, and percentage of fPSA to tPSA (%fPSA) (standard tests) and the number of prostate biopsies that could be spared using these tests. Multivariable logistic regression models were complemented by predictive accuracy analysis and decision curve analysis.
  
  
  CONCLUSIONS
  Of >646 patients, PCa was diagnosed in 264 (40.1%). Median tPSA (5.7 vs 5.8 ng/ml; p=0.942) and p2PSA (15.0 vs 14.7 pg/ml) did not differ between groups; conversely, median fPSA (0.7 vs 1 ng/ml; p<0.001), %fPSA (0.14 vs 0.17; p<0.001), %p2PSA (2.1 vs 1.6; p<0.001), and PHI (48.2 vs 38; p<0.001) did differ significantly between men with and without PCa. In multivariable logistic regression models, p2PSA, %p2PSA, and PHI significantly increased the accuracy of the base multivariable model by 6.4%, 5.6%, and 6.4%, respectively (all p<0.001). At a PHI cut-off of 27.6, a total of 100 (15.5%) biopsies could have been avoided. The main limitation is that cases were selected on the basis of their initial tPSA values.
  
  
  CONCLUSIONS
  In patients with a tPSA range of 2-10 ng/ml, %p2PSA and PHI are the strongest predictors of PCa at initial biopsy and are significantly more accurate than tPSA and %fPSA.
authors: Department of Urology, Ospedale San Raffaele Turro, San Raffaele Scientific Institute, Milan, Italy. lazzeri.maximus@gmail.com
authors: Massimo
authors: M
authors: Lazzeri
authors: Alexander
authors: A
authors: Haese
authors: Alexandre
authors: A
authors: de la Taille
authors: Joan
authors: J
authors: Palou Redorta
authors: Thomas
authors: T
authors: McNicholas
authors: Giovanni
authors: G
authors: Lughezzani
authors: Vincenzo
authors: V
authors: Scattoni
authors: Vittorio
authors: V
authors: Bini
authors: Massimo
authors: M
authors: Freschi
authors: Amy
authors: A
authors: Sussman
authors: Bijan
authors: B
authors: Ghaleh
authors: Philippe
authors: P
authors: Le Corvoisier
authors: Josep
authors: J
authors: Alberola Bou
authors: Salvador
authors: S
authors: Esquena Fernández
authors: Markus
authors: M
authors: Graefen
authors: Giorgio
authors: G
authors: Guazzoni
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis*; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D001706:Biopsy; D015331:Cohort Studies; D003951:Diagnostic Errors; D006801:Humans; D007610:Kallikreins / Q000097:blood*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D011446:Prospective Studies; D011467:Prostate / Q000473:pathology; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000097:blood / Q000175:diagnosis*; D011498:Protein Precursors / Q000097:blood*; D012372:ROC Curve
chemical_list: C583834:(-2)pro-prostate-specific antigen, human; D014408:Biomarkers, Tumor; D011498:Protein Precursors; C549870:KLK3 protein, human; D007610:Kallikreins; D017430:Prostate-Specific Antigen