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Prostate kallikrein markers in diagnosis, risk stratification and prognosis

Nature Reviews Urology volume 6, pages 384–391 (2009)Cite this article

Abstract

The kallikrein, prostate-specific antigen (PSA), is one of the world's most frequently used disease biomarkers. After almost two decades of research and clinical experience, the diagnostic and monitoring limitations of PSA are beginning to be understood. Most physicians are aware of PSA's low specificity for cancer among older men with benign prostatic conditions; fewer are aware of recent data, which show that a prior negative biopsy or a prior PSA value below the threshold for biopsy might compromise the predictive accuracy of PSA even further. Furthermore, a subtle increase in serum PSA level during early middle age is strongly correlated with clinically important prostate cancer. We review current and past reports on the prostate kallikreins PSA and hK2 in relation to pathology and epidemiology.

Key Points

  • A single measurement of serum PSA level during early middle age is a powerful tool for predicting the risk of subsequent prostate cancer development

  • Measuring levels of PSA subforms and of human kallikrein-related peptidase 2, in addition to total PSA, could enhance predictive accuracy in older men

  • PSA dynamics, such as velocity and doubling time, add little to the predictive power of total PSA alone

  • PSA-based screening might prevent about 20% of prostate cancer-related deaths, but is associated with substantial overdiagnosis

  • Currently, nothing can predict if and when a prostatic tumor will progress to life-threatening disease beyond current established predictors such as total PSA, tumor grade and clinical stage

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Acknowledgements

This research was funded by a P50-CA92629 Specialized Program of Research Excellence and a R21-CA127768 phased innovation grant in cancer prognosis and prediction from the National Cancer Institute, Swedish Cancer Society project numbers 3555 and 07-0458, European Union 6th Framework contract LSHC-CT-2004-503011 (P-Mark), and Swedish Research Council (Medicine) project numbers 20095 and 20760. M. F. O'Brien was funded by the Boxer Family Fellowship, supported by The Sidney Kimmel Center for Prostate and Urologic Cancers. We thank Janet Novak of Helix Editing for substantive editing of the manuscript; this work was funded by Memorial Sloan–Kettering Cancer Center.

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Authors and Affiliations

  1. Department of Urology, University Hospital Malmö, Lund University, Sweden

    David Ulmert & Anders S. Bjartell

  2. Department of Clinical Laboratories, Memorial Sloan–Kettering Cancer Center, New York, NY, USA

    Hans Lilja

  3. Department of Surgery, Memorial Sloan–Kettering Cancer Center, New York, NY, USA

    M. Frank O'Brien & Hans Lilja

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Correspondence to Hans Lilja.

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Competing interests

H. Lilja declares that he holds patents for free and complexed PSA (US5501983 [1996], EP540573 [1996], US5912158 [1999], US5939,533 [1999]) and for hK2 (US5614,372 [1997], EP8011164 [1997]). The other authors declare no competing interests.

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Ulmert, D., O'Brien, M., Bjartell, A. et al. Prostate kallikrein markers in diagnosis, risk stratification and prognosis. Nat Rev Urol 6, 384–391 (2009). https://doi.org/10.1038/nrurol.2009.123

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