title: Multicenter European external validation of a prostate health index-based nomogram for predicting prostate cancer at extended biopsy.
abstract: BACKGROUND
  External validation of a prediction tool is mandatory to assess the tool's accuracy and generalizability within different patient cohorts.
  
  
  OBJECTIVE
  To externally validate a previously developed Prostate Health Index (PHI)-based nomogram for predicting the presence of prostate cancer (PCa) at biopsy.
  
  
  METHODS
  The study population consisted of 883 patients who were scheduled for a prostate biopsy at one of five European tertiary care centers. Total prostate-specific antigen (tPSA), free prostate-specific antigen (fPSA), and [-2]pro-prostate-specific antigen (p2PSA) levels were determined. The fPSA-to-tPSA ratio (%fPSA), p2PSA, and PHI ([p2PSA / fPSA] × √tPSA) were calculated.
  
  
  METHODS
  Extended initial and repeat prostate biopsy.
  
  
  METHODS
  Logistic regression models were fitted to test the predictors of PCa and to determine their predictive accuracy. A calibration plot was used to evaluate the extent of overestimation or underestimation between nomogram predictions and observed PCa rate. Decision curve analysis (DCA) provided an estimate of the net benefit obtained by using the PHI-based nomogram.
  
  
  CONCLUSIONS
  Of 833 patients, 365 (41.3%) were diagnosed with PCa at extended prostate biopsy. In accuracy analyses, PHI was the most informative predictor of PCa (0.68), outperforming tPSA (0.51) and %fPSA (0.64). The predictive accuracy of the previously developed nomogram was 75.2% (95% confidence interval, 71.4-78.1). Calibration of the nomogram was good in patients at a low to intermediate predicted probability of PCa, while calibration was suboptimal, with a tendency to overestimate the presence of PCa, in high-risk patients. Finally, DCA demonstrated that the use of the PHI-based nomogram resulted in the highest net benefit. The main limitation of the study is the fact that only Caucasian patients were included.
  
  
  CONCLUSIONS
  At external validation, the previously developed PHI-based nomogram confirmed its ability to determine the presence of PCa at biopsy. These findings provide further evidence supporting the potential role of the nomogram in the biopsy decision pathway for European men with suspected PCa.
  
  
  RESULTS
  In the current study, we externally validated a Prostate Health Index-based nomogram to predict the presence of prostate cancer (PCa) at biopsy. This tool may help clinicians determine the need for a prostate biopsy in European patients with suspected PCa.
authors.affiliation: Department of Urology, San Raffaele Turro, Vita-Salute San Raffaele University, Milan, Italy. Electronic address: lughezzani.giovanni@hsr.it.
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: Massimo
authors.initials: M
authors.lastname: Lazzeri
authors.affiliation: Martini-Clinic Prostate Cancer Center, University Clinic Hamburg, Eppendorf Hamburg, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Haese
authors.affiliation: South Bedfordshire & Hertfordshire Urological Cancer Centre, Lister Hospital, Stevenage, UK.
authors.forename: Thomas
authors.initials: T
authors.lastname: McNicholas
authors.affiliation: Department of Urology, INSERM U955Eq07 APHP Mondor Hospital, Créteil, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: de la Taille
authors.affiliation: Department of Urology, San Raffaele Turro, Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Nicolò Maria
authors.initials: NM
authors.lastname: Buffi
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, 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: Alessandro
authors.initials: A
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: Urologic Oncology Section of the Department of Urology and Radiology Department, Fundació Puigvert, Cartagena, Barcelona, Spain.
authors.forename: Joan
authors.initials: J
authors.lastname: Palou Redorta
authors.affiliation: Martini-Clinic Prostate Cancer Center, University Clinic Hamburg, Eppendorf Hamburg, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Graefen
authors.affiliation: Department of Urology, San Raffaele Turro, Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Guazzoni
mesh_terms: D000368:Aged; D001706:Biopsy; D003661:Decision Support Techniques; D005060:Europe / Q000453:epidemiology; D006304:Health Status; D006305:Health Status Indicators; D006801:Humans; D007610:Kallikreins / Q000097:blood*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D049451:Nomograms; D018579:Patient Selection; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000097:blood* / Q000208:ethnology / Q000473:pathology*; D011498:Protein Precursors / Q000097:blood*; D015203:Reproducibility of Results; D012307:Risk Factors; D062606:Tertiary Care Centers; D044465:White People
chemical_list: C583834:(-2)pro-prostate-specific antigen, human; D011498:Protein Precursors; C549870:KLK3 protein, human; D007610:Kallikreins; D017430:Prostate-Specific Antigen
keywords: External validation; Nomogram; Prostate Health Index; Prostate biopsy; Prostate cancer