As treatment paradigms for prostate cancer have drastically changed over the past decade and most low-grade cancers are now safely monitored with active surveillance, the need for effective screening tools that adequately risk-stratify patients prior to considering prostate biopsy is more important than ever. Liquid biomarkers 4Kscore® and ExosomeDxTM were developed to identify patients at risk for high-grade prostate cancer (here defined as Gleason grade 2 or higher). Multiparametric magnetic resonance imaging (mpMRI) has also been proposed as an imaging-based screening tool prior to prostate biopsy, however, it is unclear when and how to combine mpMRI with liquid biomarkers.