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 Journal Article


Authors: Carlsson, S.; Maschino, A.; Schroder, F.; Bangma, C.; Steyerberg, E. W.; van der Kwast, T.; van Leenders, G.; Vickers, A.; Lilja, H.; Roobol, M. J.
Article 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. Design, setting, and participants 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. Outcome measurements and statistical analysis We calculated the accuracy (area under the curve [AUC]) of statistical models to predict pathologically aggressive PCa (pT3-T4, extracapsular extension, tumor volume >0.5 cm3, or any Gleason grade ≥4) based on clinical predictors (age, stage, PSA, biopsy findings) with and without levels of four kallikrein markers in blood. Results and limitations 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. © 2013 European Association of Urology.
Keywords: mass screening; prostatic neoplasms; radical prostatectomy; kallikrein-related peptidases; prostate-specific antigen/blood
Journal Title: European Urology
Volume: 64
Issue: 5
ISSN: 0302-2838
Publisher: Elsevier Science, Inc.  
Date Published: 2013-11-01
Start Page: 693
End Page: 699
Language: English
DOI: 10.1016/j.eururo.2013.04.040
PROVIDER: scopus
PMCID: PMC3786059
PUBMED: 23683475
DOI/URL:
Notes: --- - Cited By (since 1996):1 - "Export Date: 1 November 2013" - "CODEN: EUURA" - "Source: Scopus"
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MSK Authors
  1. Hans Gosta Lilja
    286 Lilja
  2. Andrew J Vickers
    560 Vickers