title: Initial prostate biopsy: development and internal validation of a biopsy-specific nomogram based on the prostate cancer antigen 3 assay.
abstract: BACKGROUND
  Urinary prostate cancer antigen 3 (PCA3) assay in combination with established clinical risk factors improves the identification of men at risk of harboring prostate cancer (PCa) at initial biopsy (IBX).
  
  
  OBJECTIVE
  To develop and validate internally the first IBX-specific PCA3-based nomogram that allows an individual assessment of a man's risk of harboring any PCa and high-grade PCa (HGPCa).
  
  
  METHODS
  Clinical and biopsy data including urinary PCA3 score of 692 referred IBX men at risk of PCa were collected within two prospective multi-institutional studies.
  
  
  METHODS
  IBX (≥ 10 biopsy cores) with standard risk factor assessment including prebiopsy urinary PCA3 measurement.
  
  
  METHODS
  PCA3 assay cut-off thresholds were investigated. Regression coefficients of logistic risk factor analyses were used to construct specific sets of PCA3-based nomograms to predict any PCa and HGPCa at IBX. Accuracy estimates for the presence of any PCa and HGPCa were quantified using area under the curve of the receiver operator characteristic analysis and compared with a clinical model. Bootstrap resamples were used for internal validation. Decision curve analyses quantified the clinical net benefit related to the novel PCA3-based IBX nomogram versus the clinical model.
  
  
  CONCLUSIONS
  Any PCa and HGPCa were diagnosed in 46% (n=318) and 20% (n=137), respectively. Age, prostate-specific antigen, digital rectal examination, prostate volume, and PCA3 were independent predictors of PCa at IBX (all p<0.001). The PCA3-based IBX nomograms significantly outperformed the clinical models without PCA3 (all p<0.001). Accuracy was increased by 4.5-7.1% related to PCA3 inclusion. When applying nomogram-derived PCa probability thresholds ≤ 30%, only a few patients with HGPCa (≤ 2%) will be missed while avoiding up to 55% of unnecessary biopsies. External validation of the PCA3-based IBX-specific nomogram is warranted.
  
  
  CONCLUSIONS
  The internally validated PCA3-based IBX-specific nomogram outperforms a clinical prediction model without PCA3 for the prediction of any PCa, leading to the avoidance of unnecessary biopsies while missing only a few cases of HGPCa. Our findings support the concepts of a combination of novel markers with established clinical risk factors and the superiority of decision tools that are specific to a clinical scenario.
authors.affiliation: Department of Urology, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Hansen
authors.forename: Marco
authors.initials: M
authors.lastname: Auprich
authors.forename: Sascha A
authors.initials: SA
authors.lastname: Ahyai
authors.forename: Alexandre
authors.initials: A
authors.lastname: de la Taille
authors.forename: Hendrik
authors.initials: H
authors.lastname: van Poppel
authors.forename: Michael
authors.initials: M
authors.lastname: Marberger
authors.forename: Arnulf
authors.initials: A
authors.lastname: Stenzl
authors.forename: Peter F A
authors.initials: PF
authors.lastname: Mulders
authors.forename: Hartwig
authors.initials: H
authors.lastname: Huland
authors.forename: Margit
authors.initials: M
authors.lastname: Fisch
authors.forename: Clement-Claude
authors.initials: CC
authors.lastname: Abbou
authors.forename: Jack A
authors.initials: JA
authors.lastname: Schalken
authors.forename: Yves
authors.initials: Y
authors.lastname: Fradet
authors.forename: Leonard S
authors.initials: LS
authors.lastname: Marks
authors.forename: William
authors.initials: W
authors.lastname: Ellis
authors.forename: Alan W
authors.initials: AW
authors.lastname: Partin
authors.forename: Karl
authors.initials: K
authors.lastname: Pummer
authors.forename: Markus
authors.initials: M
authors.lastname: Graefen
authors.forename: Alexander
authors.initials: A
authors.lastname: Haese
authors.forename: Jochen
authors.initials: J
authors.lastname: Walz
authors.forename: Alberto
authors.initials: A
authors.lastname: Briganti
authors.forename: Shahrokh F
authors.initials: SF
authors.lastname: Shariat
authors.forename: Felix K
authors.initials: FK
authors.lastname: Chun
mesh_terms: D000367:Age Factors; D000368:Aged; D000951:Antigens, Neoplasm / Q000652:urine*; D015415:Biomarkers / Q000652:urine; D062005:Biopsy, Large-Core Needle; D015331:Cohort Studies; D003661:Decision Support Techniques; D051517:Digital Rectal Examination / Q000706:statistics & numerical data; D006801:Humans; D007610:Kallikreins / Q000097:blood; D008297:Male; D008875:Middle Aged; D049451:Nomograms; D009929:Organ Size; D011446:Prospective Studies; D011467:Prostate / Q000473:pathology*; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000175:diagnosis*; D015203:Reproducibility of Results; D018570:Risk Assessment / Q000379:methods; D012307:Risk Factors
chemical_list: D000951:Antigens, Neoplasm; D015415:Biomarkers; C479341:prostate cancer antigen 3, human; C549870:KLK3 protein, human; D007610:Kallikreins; D017430:Prostate-Specific Antigen