Effectiveness and cost-effectiveness of risk-adapted colorectal cancer screening: a randomized controlled trial and modeling analysis

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 3 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. Trial registration: Chinese Clinical Trial Registry (ChiCTR1800015506).