摘要Background:More efficacious,noninvasive screening methods are needed for advanced colorectal neoplasia.miR-92a is a reliable and reproducible biomarker for early colorectal cancer detection in stool samples.We compared the diagnostic efficacies of miR-92a,immunochemical fecal occult blood testing(FIT),and their combination(FIT+miR-92a)in a prospective multicenter screening trial.Methods:Overall,16,240 participants aged 30-75 years were enrolled between April 1,2021,and December 31,2023.A total of 15,586 participants returned samples available for both FIT and miR-92a tests.All those with positive,and a random selection of those with negative screening tests were recommended to undergo colonoscopy.Follow-ups were performed until participants completed the colonoscopic examination.A total of 1401 screen-positive and 2079 randomly selected screen-negative individuals completed colonoscopies.Primary outcomes included sensitivity,number needed to screen(NNS),Youden index and receiver operating characteristic area under the curve(AUC)for advanced adenomas and colorectal cancer[advanced neoplasia(AN)]for each screening modality in the diagnostic performance analysis.Results:Colonoscopy was performed in 3480 individuals.The colonoscopy compliance rate was 47.8%for screen-positive individuals.The sensitivity of miR-92a vs.FIT for AN was 70.9%vs.54.3%(P<0.001),NNS was 24.7 vs.32.2(P=0.001),Youden index was 47.9%vs.35.0%(P<0.001),AUC was 0.74 vs.0.67(P=0.010).FIT+miR-92a had a sensitivity of 85.4%,an NNS of 20.5,a Youden index of 47.9%and an AUC of 0.74 for AN.Conclusions:For AN screening,miR-92a demonstrated better sensitivity,NNS,Youden index and AUC as compared with FIT.Compared with FIT,using miR-92a appears to be more efficient for population-based screening programs.Screening sensitivity for AN can be further enhanced if conditionally used in combination with FIT.