title: Reducing unnecessary biopsy during prostate cancer screening using a four-kallikrein panel: an independent replication.
abstract: OBJECTIVE
  We previously reported that a panel of four kallikrein forms in blood-total, free, and intact prostate-specific antigen (PSA) and kallikrein-related peptidase 2 (hK2)-can reduce unnecessary biopsy in previously unscreened men with elevated total PSA. We aimed to replicate our findings in a large, independent, representative, population-based cohort.
  
  
  METHODS
  The study cohort included 2,914 previously unscreened men undergoing biopsy as a result of elevated PSA (> or = 3 ng/mL) in the European Randomized Study of Screening for Prostate Cancer, Rotterdam, with 807 prostate cancers (28%) detected. The cohort was randomly divided 1:3 into a training and validation set. Levels of kallikrein markers were compared with biopsy outcome.
  
  
  RESULTS
  Addition of free PSA, intact PSA, and hK2 to a model containing total PSA and age improved the area under the curve from 0.64 to 0.76 and 0.70 to 0.78 for models without and with digital rectal examination results, respectively (P < .001 for both). Application of the panel to 1,000 men with elevated PSA would reduce the number of biopsies by 513 and miss 54 of 177 low-grade cancers and 12 of 100 high-grade cancers. Findings were robust to sensitivity analysis.
  
  
  CONCLUSIONS
  We have replicated our previously published finding that a panel of four kallikreins can predict the result of biopsy for prostate cancer in men with elevated PSA. Use of this panel would dramatically reduce biopsy rates. A small number of men with cancer would be advised against immediate biopsy, but these men would have predominately low-stage, low-grade disease.
authors.affiliation: Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. vickersa@mskcc.org
authors.forename: Andrew
authors.initials: A
authors.lastname: Vickers
authors.forename: Angel
authors.initials: A
authors.lastname: Cronin
authors.forename: Monique
authors.initials: M
authors.lastname: Roobol
authors.forename: Caroline
authors.initials: C
authors.lastname: Savage
authors.forename: Mari
authors.initials: M
authors.lastname: Peltola
authors.forename: Kim
authors.initials: K
authors.lastname: Pettersson
authors.forename: Peter T
authors.initials: PT
authors.lastname: Scardino
authors.forename: Fritz
authors.initials: F
authors.lastname: Schröder
authors.forename: Hans
authors.initials: H
authors.lastname: Lilja
mesh_terms: D000368:Aged; D001706:Biopsy; D015331:Cohort Studies; D055088:Early Detection of Cancer / Q000379:methods; D006801:Humans; D007610:Kallikreins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000097:blood* / Q000473:pathology
chemical_list: D007610:Kallikreins; D017430:Prostate-Specific Antigen