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ObjectivesTo evaluate the performance of mpMRI and the 4Kscore test together for the detection of significant prostate cancer.Material and methodsWe selected a consecutive series of men who were referred for evaluation of prostate cancer at an academic institution and underwent mpMRI and the 4Kscore test. The primary outcome was the presence of Gleason 7 or higher cancer on biopsy of the prostate. We used logistic regression and Decision Curve Analysis to report the discrimination and clinical utility of using mpMRI and the 4Kscore test for prostate cancer detection. We modeled the probability of harboring a Gleason 7 or higher prostate cancer based on the 4Kscore test and mpMRI findings. Finally, we examined various combinations and sequences of mpMRI and the 4Kscore test and assessed the impact on biopsies avoided and cancers missed.ResultsAmong 300 men who underwent a 4Kscore test and mpMRI, 149 (49%) underwent a biopsy. Among those, 73 (49%) had cancer, and 49 (33%) had Gleason 7 cancer. The area under the curve (AUC) for using the 4Kscore test and mpMRI together 0.82 (0.75–0.89) was superior to using the 4Kscore 0.70 (0.62–0.79) or mpMRI 0.74 (0.66–0.81) individually (p = 0.001). Similarly, decision analysis revealed the highest net benefit was achieved using both tests.ConclusionsThe 4Kscore test and mpMRI results provide independent, but complementary, information that enhances the prediction of higher-grade prostate cancer and improves patient’s selection for a prostate biopsy. Prospective trials are required to confirm these findings.