Molecular Biomarkers for the Detection of Clinically Significant Prostate Cancer: A Systematic Review and Meta-analysis

CONTEXT: Prostate cancer (PCa) is the second most common type of cancer in men. Individualized risk stratification is crucial to adjust decision-making. A variety of molecular biomarkers have been developed in order to identify patients at risk of clinically significant PCa (csPCa) defined by the most common PCa risk stratification systems. OBJECTIVE: The present study aims to examine the effectiveness (diagnostic accuracy) of blood or urine-based PCa biomarkers to identify patients at high risk of csPCa. EVIDENCE ACQUISITION: A systematic review of the literature was conducted. Medline and EMBASE were searched from inception to March 2021. Randomized or nonrandomized clinical trials, and cohort and case-control studies were eligible for inclusion. Risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. Pooled estimates of sensitivity, specificity, and area under the curve were obtained. EVIDENCE SYNTHESIS: Sixty-five studies (N = 34 287) were included. Not all studies included prostate-specific antigen-selected patients. The pooled data showed that the Prostate Health Index (PHI), with any cutoff point between 15 and 30, had sensitivity of 0.95–1.00 and specificity of 0.14–0.33 for csPCa detection. The pooled estimates for SelectMDx test sensitivity and specificity were 0.84 and 0.49, respectively. CONCLUSIONS: The PHI test has a high diagnostic accuracy rate for csPCa detection, and its incorporation in the diagnostic process could reduce unnecessary biopsies. However, there is a lack of evidence on patient-important outcomes and thus more research is needed. PATIENT SUMMARY: It has been possible to verify that the application of biomarkers could help detect prostate cancer (PCa) patients with a higher risk of poorer evolution. The Prostate Health Index shows an ability to identify 95–100 for every 100 patients suffering from clinically significant PCa who take the test, preventing unnecessary biopsies in 14–33% of men without PCa or insignificant PCa.