Prostate specific antigen (PSA) and digital rectal exam (DRE) have low specificity for the detection of prostate cancer (PCa) and poorly predict the presence of aggressive disease. Urine is readily available, non-invasive, and represents a promising source of biomarkers for early detection and prediction of PCa prognosis. The goal of this review is to identify promising biomarkers for urine-based PCa, examine trends, and outline potential pitfalls.
Pubmed® and Web of Science® database searches of peer-reviewed literature on urine-based testing in PCa were performed. Original studies on this subject, as well as a small number of reviews, were analyzed including the strengths and weaknesses. We provide a comprehensive review of urine-based testing for PCa that covers the technical aspects including the methodology of urine collection, as well as recent developments in biomarkers spanning the fields of genomics, epigenetics, transcriptomics, proteomics, and metabolomics.
The process of urine collection is subject to variability, which may result in conflicting clinical results. Detecting PCa in urine is technically feasible as demonstrated by numerous “proof-of principle” studies, but few markers have been validated in multiple large sample sets. Biomarker development using urine has been accelerating in recent years, with numerous studies identifying DNA, RNA, protein, and metabolite-based biomarkers in the urine. Advanced clinical studies have identified PCA3 and TMPRSS2:ERG fusion transcripts as promising RNA markers for cancer detection and possibly prognosis. DNA methylation analysis of multiple genes improves specificity, and represents a promising platform for the development of clinical-grade assays.
Urine-based testing is non-invasive and represents a rich source of novel biomarkers for PCa. Although urine demonstrates promise in detecting cancer, the ability to identify aggressive subsets of PCa needs further development.