Biomarkers for prostate cancer detection

Purpose: The limitations of prostate specific antigen as a biomarker for prostate cancer screening, characterized by low sensitivity for acceptable false-positive rates, are well known. New markers that differentiate indolent from aggressive cancers to decrease potential the over treatment of prostate cancer are needed. We reviewed current and potential biomarkers for prostate cancer detection. Materials and Methods: A literature search was performed to identify established and emerging biomarkers for prostate cancer detection. Recent suggested guidelines by the Early Detection Research Network for phases of biomarker studies were interpreted for use in prostate cancer and the existing status of marker studies were reviewed with respect to these phases of study. Results: Advances in high throughput bench research, including high dimensional genomic, proteomic and autoantibody signatures, have the potential to improve the operating characteristics of prostate specific antigen but they are undergoing reproducibility and multicenter validation studies. None of the prostate specific antigen derivatives or isoforms, such as prostate specific antigen density, velocity or percent complexed prostate specific antigen, improve operating characteristics enough to likely replace prostate specific antigen. Prostate stem cell antigen, alpha-methyl coenzyme-A racemase, PCA3, early prostate cancer antigen, human kallikrein 2 and hepsin are promising markers that are currently undergoing validation. Conclusions: The process of discovering novel biomarkers to replace or augment the existing best marker, prostate specific antigen, requires standardized phases of evaluation and validation. Several biomarkers are currently on the cusp of initial validation studies.