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This study aims to compare outcomes of risk-adapted CRC screening with colonoscopy and fecal immunochemical test (FIT) strategies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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\u201374\u00a0years 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\u00a0years using MIMIC-CRC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      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 (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&gt;\u20090.05). 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\u00a0years, 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.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration<\/jats:title>\n                    <jats:p>Chinese Clinical Trial Registry (ChiCTR1800015506).<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s40779-025-00671-7","type":"journal-article","created":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T04:12:28Z","timestamp":1763957548000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Effectiveness and cost-effectiveness of risk-adapted colorectal cancer screening: a randomized controlled trial and modeling analysis"],"prefix":"10.1016","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6171-1162","authenticated-orcid":false,"given":"Hong-Da","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ju-Fang","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue-Yang","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling-Bin","family":"Du","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xian-Zhen","family":"Liao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong-Hua","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong-Biao","family":"Ying","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-Fang","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shi-Peng","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hai-Fan","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun-Xin","family":"Kong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fu-Rong","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia-Hui","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen-Yu","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hermann","family":"Brenner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Dai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","published-online":{"date-parts":[[2025,11,24]]},"reference":[{"issue":"3","key":"671_CR1","first-page":"229","volume":"74","author":"F Bray","year":"2024","unstructured":"Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, et al. 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