Prospective validation study of a novel integrated pathway based on clinical features, MRI biomarkers and microRNAs for early detection of prostate cancer

Background: Prostate cancer (PCa) is the most diagnosed cancer in men, with anincreasing need to integrate noninvasive imaging and circulating microRNAs beyondprostate-specific antigen for screening and early detection.Objective: To validate magnetic resonance imaging (MRI) biomarkers and circulatingmicroRNAs as triage tests for patients directed to prostate biopsy, and to test differentdiagnostic pathways to compare their performance on patients' outcome, in terms ofunnecessary biopsy avoidance.Design, setting, and participants: A prospective single-center cohort study, enrollingpatients with PCa suspicion who underwent MRI, MRI-directed fusion biopsy (MRDB),and circulating microRNAs, was conducted. A network-based analysis was used to identify MRI biomarkers and microRNA drivers of clinically significant PCa.Intervention: MRI, MRDB, and blood sampling.Outcome measurements and statistical analysis: The decision curve analysis wasexploited to assess the performance of the proposed diagnostic pathways and to quantify their benefit in terms of biopsy avoidance.Results and limitations: Overall, 261 men were enrolled and underwent MRDB for PCadetection. A total of 178 patients represented the entire cohort: 55 (30.9%) were negativefor PCa, 39 (21.9%) had grade group (GG) 1 PCa, and 84 (47.2%) had GG >1 PCa. The proposed integrated pathway, including clinical data, MRI biomarkers, and microRNAs, provided the best net benefit with a biopsy avoidance rate of about 20% at a low diseaseprobability. The main limitation is the monocentric design in a referral center.Conclusions: The integrated pathway represents a validated model that sees MRIbiomarkers and microRNAs as a prebiopsy triage of patients at a risk for clinically significant PCa. The proposed pathway showed the highest net benefit in terms of unnecessarybiopsy avoidance.