摘要Background:Risk-adapted colorectal cancer(CRC)screening has the potential to balance effectiveness with resource demands,yet evidence comparing it with established methods remains limited.This study aims to compare outcomes of risk-adapted CRC screening with colonoscopy and fecal immunochemical test(FIT)strategies.Methods:We adopted a hybrid methodology combining real-world data from a population-based CRC screening randomized controlled trial(TARGET-C)with projections from a validated Markov-based microsimulation model(MIMIC-CRC).The TARGET-C trial enrolled 19,582 participants aged 50-74 years from 6 centers in China,randomized in a 1:2:2 ratio into three groups.After applying the exclusion criteria,the final analysis included 3883 participants in the one-time colonoscopy group,7793 in the annual FIT group,and 7697 in the risk-adapted screening group.In the latter group,screening allocation was determined by a composite risk score incorporating age,sex,family history of CRC,smoking status,and body mass index,with high-risk participants referred for colonoscopy and low-risk participants for FIT.The primary outcome was detection rates of advanced neoplasm(CRC and advanced adenoma)over 4 rounds.Secondary outcomes included screening participation,colonoscopy demand,and costs from a societal perspective.Long-term effectiveness and cost-effectiveness were modeled over 15 years using MIMIC-CRC.Results:Across 4 rounds,overall participation rates(attending at least one screening round)were 42.3%(colonoscopy),99.8%(FIT),and 92.5%(risk-adapted).Detection rates of advanced neoplasms were 2.8%,2.3%,and 2.6%,respectively,with no significant differences(P>0.05).Colonoscopies needed to detect 1 advanced neoplasm were 15.4,7.9,and 9.3,respectively.From a societal perspective,the cost for detecting 1 advanced neoplasm was 15,341,21,754,and 24,300 Chinese Yuan,respectively.Over 15 years,risk-adapted screening reduced incidence by 16.7%and mortality by 21.5%compared with no screening,slightly less effective than colonoscopy(24.6%and 24.8%,respectively).Under observed real-world adherence,colonoscopy was the most cost-effective;under perfect full adherence,risk-adapted screening was the most cost-effective.Conclusions:In this population-based CRC screening trial,risk-adapted screening,colonoscopy,and FIT demonstrated comparable effectiveness,but differed in participation rates,resource utilization,and cost-effectiveness.Risk-adapted screening could serve as a complementary approach to established strategies,particularly when health resources are limited.