title: Predictive value of four kallikrein markers for pathologically insignificant compared with aggressive prostate cancer in radical prostatectomy specimens: results from the European Randomized Study of Screening for Prostate Cancer section Rotterdam.
abstract: BACKGROUND
  Treatment decisions can be difficult in men with low-risk prostate cancer (PCa).
  
  
  OBJECTIVE
  To evaluate the ability of a panel of four kallikrein markers in blood-total prostate-specific antigen (PSA), free PSA, intact PSA, and kallikrein-related peptidase 2-to distinguish between pathologically insignificant and aggressive disease on pathologic examination of radical prostatectomy (RP) specimens as well as to calculate the number of avoidable surgeries.
  
  
  METHODS
  The cohort comprised 392 screened men participating in rounds 1 and 2 of the Rotterdam arm of the European Randomized Study of Screening for Prostate Cancer. Patients were diagnosed with PCa because of an elevated PSA ≥3.0 ng/ml and were treated with RP between 1994 and 2004.
  
  
  METHODS
  We calculated the accuracy (area under the curve [AUC]) of statistical models to predict pathologically aggressive PCa (pT3-T4, extracapsular extension, tumor volume >0.5cm(3), or any Gleason grade ≥4) based on clinical predictors (age, stage, PSA, biopsy findings) with and without levels of four kallikrein markers in blood.
  
  
  CONCLUSIONS
  A total of 261 patients (67%) had significant disease on pathologic evaluation of the RP specimen. While the clinical model had good accuracy in predicting aggressive disease, reflected in a corrected AUC of 0.81, the four kallikrein markers enhanced the base model, with an AUC of 0.84 (p < 0.0005). The model retained its ability in patients with low-risk and very-low-risk disease and in comparison with the Steyerberg nomogram, a published prediction model. Clinical application of the model incorporating the kallikrein markers would reduce rates of surgery by 135 of 1000 patients overall and 110 of 334 patients with pathologically insignificant disease. A limitation of the present study is that clinicians may be hesitant to make recommendations against active treatment on the basis of a statistical model.
  
  
  CONCLUSIONS
  Our study provided proof of principle that predictions based on levels of four kallikrein markers in blood distinguish between pathologically insignificant and aggressive disease after RP with good accuracy. In the future, clinical use of the model could potentially reduce rates of immediate unnecessary active treatment.
authors.affiliation: Department of Surgery (Urology Service), Memorial Sloan-Kettering Cancer Center, New York, NY, USA; Department of Urology, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
authors.forename: Sigrid
authors.initials: S
authors.lastname: Carlsson
authors.forename: Alexandra
authors.initials: A
authors.lastname: Maschino
authors.forename: Fritz
authors.initials: F
authors.lastname: Schröder
authors.forename: Chris
authors.initials: C
authors.lastname: Bangma
authors.forename: Ewout W
authors.initials: EW
authors.lastname: Steyerberg
authors.forename: Theo
authors.initials: T
authors.lastname: van der Kwast
authors.forename: Geert
authors.initials: G
authors.lastname: van Leenders
authors.forename: Andrew
authors.initials: A
authors.lastname: Vickers
authors.forename: Hans
authors.initials: H
authors.lastname: Lilja
authors.forename: Monique J
authors.initials: MJ
authors.lastname: Roobol
mesh_terms: D000368:Aged; D019540:Area Under Curve; D001706:Biopsy; D003661:Decision Support Techniques; D005060:Europe; D006801:Humans; D007610:Kallikreins / Q000097:blood*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D049451:Nomograms; D011237:Predictive Value of Tests; D017430:Prostate-Specific Antigen / Q000097:blood*; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000097:blood* / Q000473:pathology / Q000601:surgery*; D018570:Risk Assessment; D012307:Risk Factors; D020840:Tissue Kallikreins / Q000097:blood*; D047368:Tumor Burden; D019564:Unnecessary Procedures; D015854:Up-Regulation
chemical_list: C549870:KLK3 protein, human; D007610:Kallikreins; D020840:Tissue Kallikreins; D017430:Prostate-Specific Antigen
keywords: Kallikrein-related peptidases; Mass screening; Prostate-specific antigen/blood; Prostatic neoplasms; Radical prostatectomy