title: External validation of urinary PCA3-based nomograms to individually predict prostate biopsy outcome.
abstract: BACKGROUND
  Prior to safely adopting risk stratification tools, their performance must be tested in an external patient cohort.
  
  
  OBJECTIVE
  To assess accuracy and generalizability of previously reported, internally validated, prebiopsy prostate cancer antigen 3 (PCA3) gene-based nomograms when applied to a large, external, European cohort of men at risk of prostate cancer (PCa).
  
  
  METHODS
  Biopsy data, including urinary PCA3 score, were available for 621 men at risk of PCa who were participating in a European multi-institutional study.
  
  
  METHODS
  All patients underwent a ≥10-core prostate biopsy. Biopsy indication was based on suspicious digital rectal examination, persistently elevated prostate-specific antigen level (2.5-10 ng/ml) and/or suspicious histology (atypical small acinar proliferation of the prostate, >/= two cores affected by high-grade prostatic intraepithelial neoplasia in first set of biopsies).
  
  
  METHODS
  PCA3 scores were assessed using the Progensa assay (Gen-Probe Inc, San Diego, CA, USA). According to the previously reported nomograms, different PCA3 score codings were used. The probability of a positive biopsy was calculated using previously published logistic regression coefficients. Predicted outcomes were compared to the actual biopsy results. Accuracy was calculated using the area under the curve as a measure of discrimination; calibration was explored graphically.
  
  
  CONCLUSIONS
  Biopsy-confirmed PCa was detected in 255 (41.1%) men. Median PCA3 score of biopsy-negative versus biopsy-positive men was 20 versus 48 in the total cohort, 17 versus 47 at initial biopsy, and 37 versus 53 at repeat biopsy (all p≤0.002). External validation of all four previously reported PCA3-based nomograms demonstrated equally high accuracy (0.73-0.75) and excellent calibration. The main limitations of the study reside in its early detection setting, referral scenario, and participation of only tertiary-care centers.
  
  
  CONCLUSIONS
  In accordance with the original publication, previously developed PCA3-based nomograms achieved high accuracy and sufficient calibration. These novel nomograms represent robust tools and are thus generalizable to European men at risk of harboring PCa. Consequently, in presence of a PCA3 score, these nomograms may be safely used to assist clinicians when prostate biopsy is contemplated.
authors.affiliation: Department of Urology, Medical University Graz, Austria. marco.auprich@medunigraz.at
authors.forename: Marco
authors.initials: M
authors.lastname: Auprich
authors.forename: Alexander
authors.initials: A
authors.lastname: Haese
authors.forename: Jochen
authors.initials: J
authors.lastname: Walz
authors.forename: Karl
authors.initials: K
authors.lastname: Pummer
authors.forename: Alexandre
authors.initials: A
authors.lastname: de la Taille
authors.forename: Markus
authors.initials: M
authors.lastname: Graefen
authors.forename: Theo
authors.initials: T
authors.lastname: de Reijke
authors.forename: Margit
authors.initials: M
authors.lastname: Fisch
authors.forename: Paul
authors.initials: P
authors.lastname: Kil
authors.forename: Paolo
authors.initials: P
authors.lastname: Gontero
authors.forename: Jacques
authors.initials: J
authors.lastname: Irani
authors.forename: Felix K-H
authors.initials: FK
authors.lastname: Chun
mesh_terms: D000951:Antigens, Neoplasm / Q000652:urine*; D014408:Biomarkers, Tumor / Q000652:urine*; D001706:Biopsy; D006801:Humans; D008297:Male; D049451:Nomograms; D011237:Predictive Value of Tests; D011467:Prostate / Q000473:pathology; D019048:Prostatic Intraepithelial Neoplasia / Q000453:epidemiology / Q000473:pathology / Q000652:urine; D011471:Prostatic Neoplasms / Q000453:epidemiology / Q000473:pathology / Q000652:urine; D015203:Reproducibility of Results; D012307:Risk Factors
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; C479341:prostate cancer antigen 3, human