BERKELEY, CA (UroToday.com) - The introduction of PSA testing has radically altered how prostate cancer (PCa) is diagnosed and managed. However, controversy still exists regarding both the utility of PSA screening for reducing PCa mortality and the risks associated with PCa over-diagnosis. Furthermore, there is the problem of the heterogeneous nature of PCa foci and problem of adequately sampling and assessing foci of poor prognosis tumors.
Additional markers are therefor urgently required to supplement or replace the PSA test and improve the specificity of PCa detection and prognosis. Multiplex urine-based assays could provide the answer and have the advantage of potentially sampling PCa material from multiple tumor foci within individual prostates and providing both diagnostic and prognostic biomarkers.[1, 2, 3, 4]
It has been demonstrated that post-DRE urine samples are a rich source of biomarkers for PCa. Urine can be obtained in any urology clinic and does not require any change in routine clinical practices. Thus, post-DRE urine could be the best compromise between a minimally invasive technique and obtaining sufficient material for a correct diagnosis. However, to properly assess and validate promising urine candidates there need to be large prospective studies of urine biomarkers using robust and standardized methods for urine collection, storage, harvest and analysis of DNA, RNA, miRNA, protein, and metabolites.
Therefore, a future goal is the development of a low cost, point of care, multiplexed, urine-based detection test for PCa which could be incorporated seamlessly into routine clinical practice to better determine which patients should undergo biopsy, and to highlight those patients that have a high risk of PCa metastasis/CRPC, and which therefore require treatment at the earliest possible point in time (see Figure 1).
|Figure 1. Current and future improvement in the PCa diagnostic scheme|
In summary, the future of urine-based PCa biomarkers looks promising. Of course many of these biomarkers are at early stages of development. It remains for us to validate the many exciting candidate biomarkers that have been discovered and to discover novel markers that will help to:
- identify those men with indolent PCa, i.e, those who will not be affected by disease in their lifetimes and who do not need treatment,
- minimize the number of unnecessary PBs,
- identify men with aggressive disease, distinguishing between who will benefit from local therapy and those who are likely to fail local therapy and require adjuvant intervention, and
- find markers that may serve as surrogate end points for clinical progression or survival.
This article reviews the biomarkers for the non-invasive testing of PCa in urine, including transcriptional profiling, DNA methylation, metabolomics, and proteomics.
The article is open access and can be downloaded at www.mdpi.com/1422-0067/14/6/12620/pdf.
- Laxman B, Morris DS, Yu J, Siddiqui J, Cao J, Mehra R, Lonigro RJ, Tsodikov A, Wei JT, Tomlins SA, Chinnaiyan AM. A first-generation multiplex biomarker analysis of urine for the early detection of prostate cancer. Cancer Res. 2008, 68, 645–649.
- Rigau M, Ortega I, Mir MC, Ballesteros C, Garcia M, Llauradó M, Colás E, Pedrola N, Montes M, Sequeiros T, Ertekin T, Majem B, Planas J, Ruiz A, Abal M, Sánchez A, Morote J, Reventós J, Doll A. A Three-Gene panel on urine increases PSA specificity in the detection of prostate cancer. Prostate 2011, 71, 1736–1745.
- Payne SR, Serth J, Schostak M, Kamradt J, Strauss A, Thelen P, Model F, Day JK, Liebenberg V, Morotti A, Yamamura S, Lograsso J, Sledziewski A, Semjonow A. DNA methylation biomarkers of prostate cancer: Confirmation of candidates and evidence urine is the most sensitive body fluid for non-invasive detection. Prostate 2009, 69, 1257–1269.
- Tomlins SA, Aubin SM, Siddiqui J, Lonigro RJ, Sefton-Miller L, Miick S, Williamsen S, Hodge P, Meinke J, Blase A, Penabella Y, Day JR, Varambally R, Han B, Wood D, Wang L, Sanda MG, Rubin MA, Rhodes DR, Hollenbeck B, Sakamoto K, Silberstein JL, Fradet Y, Amberson JB, Meyers S, Palanisamy N, Rittenhouse H, Wei JT, Groskopf J, Chinnaiyan AM. Urine TMPRSS2:ERG fusion transcript stratifies prostate cancer risk in men with elevated serum PSA. Sci. Transl. Med. 2011, 3, 94ra72.
Andreas Doll as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.
Research Unit in Biomedicine and Translational Oncology, Vall d'Hebron Research Institute and Hospital and Autonomous University of Barcelona, 08035 Barcelona, Spain