The aim of this study was to investigate whether the robust integration of expression data from urinary extracellular vesicle RNA (EV-RNA) with urine proteomic metabolites can accurately predict PCa biopsy outcome. Urine samples were analyzed by mass spectrometry and NanoString gene-expression analysis. As a result, four classifiers were generated: ‘MassSpec’ (CE-MS proteomics), ‘EV-RNA’, ‘SoC’ (standard of care) and ‘ExoSpec’. The best prediction for Gs³3+4 at initial biopsy (AUC=0.83, 95% CI:0.77-0.88) was achieved by applying ‘ExoSpec’ classifier and he outperformed other predictive classifiers. In addition, the results showed that the performance of ‘ExoSpec’ could reduce unnecessary biopsies by 30%.