Clinical Utility of 4Kscore®, ExosomeDx™ and Magnetic Resonance Imaging for the Early Detection of High Grade Prostate Cancer

Purpose: We aimed to evaluate 4Kscore (R) and ExosomeDx (TM) with multi-parametric magnetic resonance imaging in the detection of high grade prostate cancer and number of biopsies avoided. Material and Methods: Patients had 1 liquid biomarker test with or without multiparametric magnetic resonance imaging. High grade prostate cancer was defined as Gleason grade group 2 or greater. The overall number of avoided biopsies (with Gleason grade 1 or less), and number of missed Gleason grade 2 or greater cancer among the biopsied patients, were determined. Results: Of the 783 patients in the overall cohort 419 (53.5%) underwent biopsy. 4Kscore and ExosomeDx scores higher than the manufacturers' cut point were associated with PI-RADS (TM) scores 3 to 5 and Gleason grade 2 or greater prostate cancer. Limiting biopsy to the men with liquid biomarker scores above the manufacturers' cut point would have resulted avoiding 29.5% to 39.9% unnecessary biopsies overall, while missing 4.0% to 4.8% Gleason grade 2 or greater prostate cancer in the biopsy group. Screening algorithms with up-front liquid biomarker testing followed by multiparametric magnetic resonance imaging if the biomarker is above the manufacturers' cut point, then followed by biopsy if the multiparametric magnetic resonance imaging is positive or if 4Kscore 20 or greater or ExosomeDx 19 or greater would have missed 4.8% to 5.6% of Gleason grade 2 or greater prostate cancer in the biopsy group while avoiding 39.4% to 43.0% biopsies and 29.5% to 39.9% multiparametric magnetic resonance imaging overall. Similar algorithms with up-front multiparametric magnetic resonance imaging followed by liquid biomarker testing for negative multiparametric magnetic resonance imaging would have missed 2.4% of Gleason grade 2 or greater prostate cancer in the biopsy group but only avoided 17.2% 19.3% biopsies overall. Conclusions: Screening algorithms with up-front liquid biomarker testing followed by multiparametric magnetic resonance imaging and biopsy at certain biomarker thresholds could reduce unnecessary biopsies, multiparametric magnetic resonance imaging and overdetection of Gleason grade 1 prostate cancer.

Automated summary

Screening algorithms with upfront liquid biomarker testing followed by multiparametric magnetic resonance imaging and biopsy at certain biomarker thresholds could reduce unnecessary biopsies, multiparametric magnetic resonance imaging, and the overdetection of Gleason grade 1 prostate cancer.