title: A Four-kallikrein Panel Predicts High-grade Cancer on Biopsy: Independent Validation in a Community Cohort.
abstract: BACKGROUND
  A statistical model based on four kallikrein markers (total prostate-specific antigen [tPSA], free PSA [fPSA], intact PSA, and human kallikrein-related peptidase 2) in blood can predict risk of Gleason score ≥7 (high-grade) cancer at prostate biopsy.
  
  
  OBJECTIVE
  To determine the value of this model in predicting high-grade cancer at biopsy in a community-based setting in which referral criteria included percentage of fPSA to tPSA (%fPSA).
  
  
  METHODS
  We evaluated the model, with or without adding blood levels of microseminoprotein-β (MSMB) in a cohort of 749 men referred for prostate biopsy due to elevated PSA (≥3 ng/ml), low %fPSA (<20%), or suspicious digital rectal examination at Skåne University Hospital, Malmö, Sweden.
  
  
  METHODS
  The kallikrein markers, with or without MSMB levels, measured in cryopreserved anticoagulated blood were combined with age in a published statistical model (Prostate Testing for Cancer and Treatment [ProtecT]) to predict high-grade cancer at biopsy. Predictive accuracy was compared with a base model.
  
  
  CONCLUSIONS
  The %fPSA was low (median: 17; interquartile range: 13-22) in this cohort because this marker was used as a referral criterion. The ProtecT model improved discrimination over age and PSA for high-grade cancer (0.777 vs 0.720; p=0.002). At one illustrative cut point, use of the panel would reduce the number of biopsies by 236 per 1000 and detect 195 of 208 (94%) but delay diagnosis of 13 of 208 high-grade cancers. MSMB levels in blood did not improve the accuracy of the panel (p=0.2).
  
  
  CONCLUSIONS
  The kallikrein model is predictive of high-grade cancer if criteria for biopsy referral also include %fPSA, and it can reduce unnecessary biopsies without missing an undue number of tumors.
  
  
  RESULTS
  We evaluated a published model to predict biopsy outcome in men biopsied due to low percentage of free to total prostate-specific antigen. The model helps reduce unnecessary biopsies without missing an undue number of high-grade cancers.
authors.affiliation: Department of Urology, University Hospital Ruhr-University Bochum, Marien Hospital Herne, Herne, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Braun
authors.affiliation: Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Sjoberg
authors.affiliation: Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Vickers
authors.affiliation: Departments of Laboratory Medicine, Medicine (Genitourinary Oncology), and Surgery (Urology), Memorial Sloan Kettering Cancer Center, New York, NY, USA; Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK; Department of Translational Medicine, Lund University, Malmö, Sweden. Electronic address: liljah@mskcc.org.
authors.forename: Hans
authors.initials: H
authors.lastname: Lilja
authors.affiliation: Department of Translational Medicine, Lund University, Malmö, Sweden.
authors.forename: Anders S
authors.initials: AS
authors.lastname: Bjartell
mesh_terms: D000368:Aged; D019540:Area Under Curve; D001706:Biopsy; D051517:Digital Rectal Examination; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007610:Kallikreins / Q000097:blood*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D011237:Predictive Value of Tests; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000097:blood* / Q000201:enzymology / Q000473:pathology; D029584:Prostatic Secretory Proteins / Q000097:blood; D012372:ROC Curve; D015203:Reproducibility of Results; D013548:Sweden; D019564:Unnecessary Procedures
chemical_list: D029584:Prostatic Secretory Proteins; C043076:beta-microseminoprotein; C000595667:KLK2 protein, human; C549870:KLK3 protein, human; D007610:Kallikreins; D017430:Prostate-Specific Antigen
keywords: Biopsy; Four-kallikrein panel; Prostate cancer; Prostate-specific antigen