BERKELEY, CA (UroToday.com) - Recently, the U.S. Preventive Services Task Force (USPSTF) recommended against Prostate Specific Antigen (PSA)-based screening for prostate cancer. This recommendation was due, in part, to the lack of a demonstrated utility of PSA-based screening to detect clinically significant tumors when serum PSA values fall into the low but detectable range of 2.5–4.0 ng/ml. Among other consequences, this recommendation reinforced the need to develop, validate, and determine the utility of other serum and/or urine transcript and protein markers as diagnostic markers for PCa.
To this end, several markers have been recently identified and tested, including prostate-specific membrane antigen (PSMA), hepsin, a-methylacyl-coenzyme A racemase (AMACR), telomerase, the serine protease TMPRSS2, d-catenin, and a prostate-specific non-coding RNA called PCA3 (formerly called DD3). When used alone or in combination with serum PSA, all demonstrate variable utilities as diagnostic or prognostic prostate cancer markers.[1, 2, 3, 4] Taken together, these studies show that additional serum biomarkers would be very valuable to distinguish among prostatic diseases in men exhibiting low but detectable serum PSA.
The studies described in our publication were intended to determine whether cytokine and/or chemokine serum proteins could be identified that might augment or replace serum PSA as a diagnostic marker for prostate cancer. We reported that the combined use of serum Eotaxin (CCL11) levels with serum PSA or PCPTRC risk analysis increases the diagnostic utility of all of these measures to detect prostate cancer, even among men exhibiting low but detectable serum PSA. Other studies have demonstrated the utility of ‘adding’ PCA3 and TMPRSS2/ERG urine transcript levels to serum PSA levels or PCPTRC risk analysis to improve prostate cancer diagnosis.
Clearly, there is a need to continue to identify and validate serum, plasma, and urine biomarkers that can be used in combination to identify men at high risk for harboring clinically significant prostate tumors. In this way, initial screening tools can be developed and tested that enable clinicians to make sound recommendations for the use of secondary diagnostic tools, such as ultrasound and needle biopsy, to accurately detect clinically significant prostate tumors.
- Cazares LH, Drake RR, Esquela-Kirscher A, Lance RS, Semmes OJ, Troyer DA. Molecular pathology of prostate cancer. Cancer Biomark. 2010;9(1-6):441-59.
- Martin NE, Mucci LA, Loda M, Depinho RA. Prognostic determinants in prostate cancer. Cancer J. 2011;17(6):429-37. PMCID: 3240856.
- Netto GJ, Cheng L. Emerging critical role of molecular testing in diagnostic genitourinary pathology. Arch Pathol Lab Med. 2012;136(4):372-90.
- Salami SS, Schmidt F, Laxman B, Regan MM, Rickman DS, Scherr D, et al. Combining urinary detection of TMPRSS2:ERG and PCA3 with serum PSA to predict diagnosis of prostate cancer. Urol Oncol. 2011. PMCID: 3210917.
- Tomlins SA, Aubin SM, Siddiqui J, Lonigro RJ, Sefton-Miller L, Miick S, et al. Urine TMPRSS2:ERG fusion transcript stratifies prostate cancer risk in men with elevated serum PSA. Sci Transl Med. 2011;3(94):94ra72. PMCID: 3245713.
Jill A. Macoska, PhD 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.
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