Blood and urine biomarkers in prostate cancer: Are we ready for reflex testing in men with an elevated prostate-specific antigen?

Abstract

Objective There is no consensus on the role of biomarkers in determining the utility of prostate biopsy in men with elevated prostate-specific antigen (PSA). There are numerous biomarkers such as prostate health index, 4Kscore, prostate cancer antigen 3, ExoDX, SelectMDx, and Mi-Prostate Score that may be useful in this decision-making process. However, it is unclear whether any of these tests are accurate and cost-effective enough to warrant being a widespread reflex test following an elevated PSA. Our goal was to report on the clinical utility of these blood and urine biomarkers in prostate cancer screening. Methods We performed a systematic review of studies published between January 2000 and October 2020 to report the available parameters and cost-effectiveness of the aforementioned diagnostic tests. We focus on the negative predictive value, the area under the curve, and the decision curve analysis in comparing reflexive tests due to their relevance in evaluating diagnostic screening tests. Results Overall, the biomarkers are roughly equivalent in predictive accuracy. Each test has additional clinical utility to the current diagnostic standard of care, but the added benefit is not substantial to justify using the test reflexively after an elevated PSA. Conclusions Our findings suggest these biomarkers should not be used in binary fashion and should be understood in the context of pre-existing risk predictors, patient's ethnicity, cost of the test, patient life-expectancy, and patient goals. There are more recent diagnostic tools such as multi-parametric magnetic resonance imaging, polygenic single-nucleotide panels, IsoPSA, and miR Sentinel tests that are promising in the realm of prostate cancer screening and need to be investigated further to be considered a consensus reflexive test in the setting of prostate cancer screening.

Native Mass Spectrometry Quantitation of α2-3-Linked N-Acetylneuraminic Acid Content of Prostate-Specific Antigen: An Accurate Liquid Biopsy for Clinically Significant Prostate Cancer

“…This is consistent with studies that have shown that serum PSA levels do not distinguish between low-grade and clinically significant PCa. − , Several other diagnostic biomarkers have been developed to improve the prediction of clinically significant PCa. Some of these include PHI, 4Kscore, and the ExoDx IntelliScore. ,− Recent reviews of these methods concluded that while all these tests have clinical utility, they do not add substantially in diagnostic value and are relatively costly to perform. , For example, the AUCs for each of these tests are 0.652, 0.67, and 0.73, respectively. In contrast, the newly developed %α23PSA assay, if used after PSA, would enable clinical laboratories to reduce unnecessary biopsies by 85% if implemented in the diagnostic pathway of localized PCa.…”

“…14,50−52 Recent reviews of these methods concluded that while all these tests have clinical utility, they do not add substantially in diagnostic value and are relatively costly to perform. 17,50 For example, the AUCs for each of these tests are 0.652, 31 0.67, 32 and 0.73, 51 respectively. In contrast, the newly developed %α23PSA assay, if used after PSA, would enable clinical laboratories to reduce unnecessary biopsies by 85% if implemented in the diagnostic pathway of localized PCa.…”

Economic evaluation of prostate cancer risk assessment methods: A cost‐effectiveness analysis using population data

“…Many biomarkers (e.g., 4 K score, prostate health index, Progensa PCA3 38–40 ) can be used as a RAT in this model. In the base case, we used the characteristics of SelectMDx, a urine‐based molecular biomarker, 41 for the RAT strategy as an illustrative example to demonstrate the functionality of our model and to make our findings comparable to previous economic evaluation studies 19,20,28 .…”

A meta-analysis for the diagnostic accuracy of SelectMDx in prostate cancer

“…SelectMDx is a novel urine-based risk score, which combines urinary biomarkers homeobox C6 (HOXC6) and distal-less homeobox 1 (DLX1) with traditional clinical factors such as age, PSA, digital rectal examination (DRE), prostate volume, and family history of PCa to assess the probability of risk of suffering clinical significant PCa (Gleason score � 7 or Grade group � 2) [17][18][19]. This risk score could reach a sensitivity of 96% and a specificity of 53% in the validation cohort [20].…”