title: Clinical performance of serum isoform [-2]proPSA (p2PSA), and its derivatives %p2PSA and the Prostate Health Index, in men aged <60 years: results from a multicentric European study.
abstract: OBJECTIVE
  To test the hypothesis that [-2]proPSA (p2PSA) and its derivatives are more accurate than total prostate-specific antigen (tPSA), free prostate-specific antigen (fPSA) and fPSA as percentage of tPSA (%fPSA) in detecting prostate cancer (PCa) in men aged <60 years.
  
  
  METHODS
  The analysis consisted of a nested case-control study from the PRO- PSA Multicentric European Study (PROMEtheuS) project. The primary outcomes were measures of sensibility, specificity and accuracy of serum p2PSA, p2PSA as percentage of fPSA (%p2PSA) and Beckman Coulter prostate health index (PHI) in men aged <60 years who had undergone a prostate biopsy. The potential reduction in the number of unnecessary biopsies and the characteristics of the potentially missed PCa cases were reported as secondary outcomes. Multivariate logistic regression models were complemented by predictive accuracy and decision-curve analyses.
  
  
  RESULTS
  Of the 1036 patients enrolled in the PROMEtheus project, 238 (22.9%) were aged < 60 years. PCa was found in 67 subjects (28.1%); p2PSA, %p2PSA and PHI values were significantly higher (P < 0.001) among these subjects, while no differences were found in tPSA, fPSA and %fPSA values. On univariate analysis, %p2PSA (area under the curve [AUC]: 0.704) and PHI (AUC: 0.7) were the most accurate predictors, and these significantly outperformed tPSA (AUC: 0.549), fPSA (AUC: 0.511) and %fPSA (AUC: 0.557) in the prediction of PCa at biopsy (P ≤ 0.001). In multivariate logistic regression models, %p2PSA and PHI achieved independent predictor status and significantly increased the accuracy of multivariate models by 6.3 and 7.6%, respectively (P ≤ 0.05).
  
  
  CONCLUSIONS
  PHI and %p2PSA are more accurate than the reference standard tests in predicting PCa in young men.
authors.affiliation: Department of Urology, San Raffaele Turro, Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Fossati
authors.affiliation: Department of Urology, Humanitas Clinical and Research Center, Humanitas University, Milan, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Lazzeri
authors.affiliation: Martini-Clinic Prostate Cancer Centre, University Clinic Hamburg, Eppendorf Hamburg, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Haese
authors.affiliation: South Bedfordshire and Hertfordshire Urological Cancer Centre, Lister Hospital, Stevenage, UK.
authors.forename: Thomas
authors.identifier: http://orcid.org/0000-0001-9971-8765
authors.initials: T
authors.lastname: McNicholas
authors.affiliation: Department of Urology, APHP Mondor Hospital, Créteil, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: de la Taille
authors.affiliation: Department of Urology, Humanitas Clinical and Research Center, Humanitas University, Milan, Italy.
authors.forename: Nicolò Maria
authors.initials: NM
authors.lastname: Buffi
authors.affiliation: Department of Urology, Humanitas Clinical and Research Center, Humanitas University, Milan, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Lughezzani
authors.affiliation: Department of Urology, San Raffaele Turro, Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Giulio Maria
authors.initials: GM
authors.lastname: Gadda
authors.affiliation: Department of Urology, San Raffaele Turro, Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Giuliana
authors.initials: G
authors.lastname: Lista
authors.affiliation: Department of Urology, San Raffaele Turro, Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Larcher
authors.affiliation: Department of Urology, San Raffaele Turro, Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Abrate
authors.affiliation: Department of Urology, San Raffaele Turro, Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Mistretta
authors.affiliation: Department of Internal Medicine, University of Perugia, Perugia, Italy.
authors.forename: Vittorio
authors.initials: V
authors.lastname: Bini
authors.affiliation: Urological Oncology Section of the Department of Urology and Radiology Department, Fundació Puigvert, Barcelona, Spain.
authors.forename: Joan Palou
authors.initials: JP
authors.lastname: Redorta
authors.affiliation: Martini-Clinic Prostate Cancer Centre, University Clinic Hamburg, Eppendorf Hamburg, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Graefen
authors.affiliation: Department of Urology, Humanitas Clinical and Research Center, Humanitas University, Milan, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Guazzoni
mesh_terms: D000367:Age Factors; D016022:Case-Control Studies; D006305:Health Status Indicators; D006801:Humans; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D011237:Predictive Value of Tests; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000453:epidemiology; D020033:Protein Isoforms; D012372:ROC Curve
chemical_list: D020033:Protein Isoforms; D017430:Prostate-Specific Antigen
keywords: PSA; p2PSA; predictive models; prostate biopsy; prostate health index; young men