Project 2 - Validation and clinical utility of a multiplex urine biomarker for identification of clinically significant prostate cancer

The long-term goal of this proposal is to enable accurate, large-scale, non-invasive detection of clinically significant prostate cancer (csPCa; Grade Group [GG]≥2), changing the current clinical approach both for those without known PCa and those already diagnosed with lower risk, clinically indolent disease. In this proposal, we will evaluate the clinical utility of a novel urine-based biomarker (MyProstateScore2 [MPS2]) for detection of csPCa through a prospective, randomized utility trial. Additionally, through large scale analysis of urine specimens in men on active surveillance, we will optimize this test for detection of csPCa in men thought to have indolent disease. We will achieve these goals through the implementation of two specific aims. In Aim 1, we will conduct a prospective, multicenter, randomized clinical utility trial in men with elevated prostate-specific antigen (PSA) presenting to the University of Michigan and our collaborating site, the Karmanos Cancer Institute, to evaluate the impact of a MPS2 biomarker-based testing approach versus a standard-of-care MRI-based approach to prostate biopsy for csPCa detection. We hypothesize that reflexive MPS2 testing at initial diagnosis will be non-inferior to an MRI-based approach with regards to csPCa detection, with reduced unnecessary biopsies and MRI use. In Aim 2, we will utilize urine samples from prospectively collected active surveillance cohorts at the University of Michigan and the Canary Prostate Active Surveillance Study (PASS) to identify patients likely to harbor or subsequently develop csPCa. We hypothesize MPS2 testing will result in substantial improvement in discriminative ability for csPCa detection compared to existing molecular or imaging strategies. The successful completion of this project will generate a novel, non-invasive urine-based biomarker with demonstrated clinical utility that is capable of rapid clinical scalability, yielding an essential, desired tool for PCa early detection.