Tumor markers in prostate cancer I: blood-based markers

Abstract

The introduction of total prostate specific antigen (total PSA) testing in blood has revolutionized the detection and management of men with prostate cancer (PCa). The objective of this review was to discuss the challenges of PCa biomarker research, definition of the type of PCa biomarkers, the statistical considerations for biomarker discovery and validation, and to review the literature regarding total PSA velocity and novel blood-based biomarkers.

Methods: An English-language literature review of the Medline database (1990 to August 2010) of published data on blood-based biomarkers and PCa was undertaken.

Results: The inherent biological variability of total PSA levels affects the interpretation of any single result. Men who will eventually develop PCa have increased total PSA levels years or decades before the cancer is diagnosed. Total PSA velocity improves predictiveness of total PSA only marginally, limiting its value for PCa screening and prognostication. The combination of PSA molecular forms and other biomarkers improve PCa detection substantially. Several novel blood-based biomarkers such as human glandular kallikrein 2 (hK2), urokinase plasminogen activator (uPA) and its receptor (uPAR), transforming growth factor-beta 1 (TGF-β1); interleukin-6 (IL-6) and its receptor (IL-6R) may help PCa diagnosis, staging, prognostication, and monitoring. Panels of biomarkers that capture the biologic potential of PCa are in the process of being validated for PCa prognostication.

Conclusions: PSA is a strong prognostic marker for long-term risk of clinically relevant cancer. However, there is a need for novel biomarkers that aid clinical decision making about biopsy and initial treatment. There is no doubt that progress will continue based on the integrated collaboration of researchers, clinicians and biomedical firms.

Figure 1

Modification of the structured phase-approach to the systematic discovery, evaluation, and validation of biomarkers[2, 3]