From the Desk of the Associate Editor: Blood-based and Urinary Prostate Cancer Biomarkers: A Review and Comparison of Novel Biomarkers for Detection and Treatment Decisions 

PSA screening has allowed for the detection of prostate cancer at curable clinical stages, and accordingly, there has been a reduction in prostate cancer-specific mortality in the PSA era.  Criticisms of PSA based screening and its utilization for decision making regarding biopsy have focused on its sensitivity, and lack of specificity for prostate cancer.  Use of PSA alone can lead to unnecessary initial and repeat biopsies, and to the detection of indolent prostate cancer, all of which cause health and economic burdens.

Development of more specific non-invasive tests for prostate cancer has occurred for decades, with an early milestone being the FDA approval of %free PSA in 1998. More recently, with an increased understanding of the natural history of localized prostate cancer, and with improvements in biotechnology there has been a flurry of interest and progress in the development of additional tests.  In the March 2017 issue of Prostate Cancer and Prostatic Diseases, Hendriks and co-authors from the Radboud University Medical Center in the Netherlands performed a thoughtful review of the use of blood and urine based biomarkers for the detection of prostate cancer and for decision making in active surveillance.  Their review covers the Prostate Health Index and 4K Score blood tests, as well as the PCA3, ExoDX Prostate, and SelectMDX urine based tests, and the combined serum and blood Mi-Prostate Score. 

Further, the June and September 2017 issues of Prostate Cancer and Prostatic Diseases contain two original articles by Tosoian et. al., and one by Heidegger et. al., describing the utility of serum based Prostate Health Index testing and PCA3 urinary testing in making decisions regarding diagnostic biopsies and for helping inform decisions for men considering active surveillance. 

What is clear from these studies is that virtually all of the commercially available tests described provide more accuracy than PSA in the detection of prostate cancer and clinically significant disease.  These findings strongly suggest that utilization of additional testing (with percent free PSA or one of these newer tests) should be standard practice for men with PSA under 10ng/ml and negative digital rectal exam considering initial biopsy.  Moreover, for men diagnosed with prostate cancer and considering surveillance, high scores on some of these tests (i.e. Prostate Health Index levels >55) should prompt increased levels of caution as these men often have extra-prostatic extension, seminal vesicle involvement, or upgrading at radical prostatectomy. 

Finally, these and other studies suggest that serum or urine testing may work as a useful adjunct even in the era of multi-parametric prostate MRI.  Unfortunately, it is not clear as to which test is ideal for a given clinical context.  As Hendriks and colleagues state in their review, there are limited head-to-head comparisons of these tests and thus, while likely benefitting greatly overlapping populations, it may never be determined if certain sub-groups of men are ideal candidates for a particular test.  Utilization of an individual test will likely come down to cost, availability, and the ease at which the test can be performed.  Regardless, it is encouraging to see significant progress in our ability to guide men who may be at risk for prostate cancer.   

Written by: Ashley Evan Ross, MD, PhD

Read the Full-Text Article Blood-based and Urinary Prostate Cancer Biomarkers: A Review and Comparison of Novel Biomarkers for Detection and Treatment Decisions

Use of the Prostate Health Index for detection of prostate cancer: results from a large academic practice
ProPSA and the Prostate Health Index as predictive markers for aggressiveness in low-risk prostate cancer—results from an international multi-center study
Longitudinal assessment of urinary PCA3 for predicting prostate cancer grade reclassification in favorable-risk men during active surveillance
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