The Role of Biomarkers and Genetics in the Diagnosis of Prostate Cancer

Context: Given the pitfalls of prostate-specific antigen (PSA) testing for screening men with asymptomatic prostate cancer (PCa), a number of novel biomarkers have recently been studied that potentially decrease false-positive PSA results and unnecessary biopsies. Objective: To review the literature on biomarkers with potential diagnostic utility for PCa by guiding the decision for initial or repeat biopsies in patients with elevated PSA. Evidence acquisition: We conducted a systematic literature review of human clinical studies on diagnostic biomarkers reporting clinicopathologic outcomes. A comprehensive search was performed in the Medline, Scopus, and Web of Science databases for articles from January 2005 through June 2015. Evidence synthesis: For men presenting with elevated PSA, especially in the 4-10 ng/ml range, who are considered for initial prostate biopsy, two serum-based assays, the Prostate Health Index and the four-kallikrein panel, can help identify patients with an increased risk of significant cancer on biopsy. In the setting of a prior negative biopsy but elevated PSA, urine-based assays detecting prostate cancer antigen 3 and/or transmembrane protease, serine2:v-ets avian erythroblastosis virus E26 oncogene homolog fusion transcript help predict the risk of high-grade cancer on subsequent biopsy. In cases with elevated PSA and an initial negative biopsy, epigenetic analysis can predict cancer diagnosis on subsequent biopsies. The combination of these novel biomarkers with existing nomograms and risk calculators leads to increased predictive accuracy and avoids unnecessary biopsies. Conclusions: Rapid strides have been made in the discovery of novel biomarkers for guiding biopsy decisions in men suspected of harboring PCa. Although some of them have been approved for specific clinical settings, most of them still await rigorously designed prospective validation studies. Patient summary: Novel urine-, serum-, and tissue-based biomarkers have been validated for guiding decisions on prostate biopsy in asymptomatic men with elevated prostate-specific antigen. Further exploration in this field may help expand their diagnostic and prognostic roles for prostate cancer. This review summarizes some of the emerging biomarkers for aiding the diagnosis of prostate cancer in men with elevated prostate-specific antigen. Further discovery of promising biomarkers and exploration of their diagnostic and prognostic roles may encourage widespread clinical use.