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A cohort decision model incorporated clinical trial inputs, real-world adherence to initial testing and follow-up colonoscopy, and CRC progression assumptions to estimate detection, stage shifts, and CRC-related outcomes. Results indicate ng mt-sDNA improves completion and earlier detection while offsetting higher test and follow-up costs through prevention and averted CRC treatment 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Cancer Screening: Integrating Real-World Adherence, Detection, and Prevention in a Cohort-Based Modeling Analysis  \nA. Mark Fendrick 1, *, Derek W. Ebner 2, Michael Dore 3, Chris Estes 4, Gustavus Aranda 4 and Mohammad Dehghani 5  \nAcademic Editor: Michael Osseis  \nReceived: 19 November 2025  \nRevised: 12 December 2025  \nAccepted: 17 December 2025  \nPublished: 20 December 2025  \nCopyright: © 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license.  \n1 Division of General Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA  \n2 Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55902, USA  \n3 Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA  \n4 Exact Sciences Corporation, Madison, WI 53719, USA  \n5 Department of Mechanical and Industrial Engineering, Northeastern University, Boston, MA 02115, USA  \n* Correspondence: [amfen@med.umich.edu](amfen@med.umich.edu)  \nAbstract  \nBackground/Objectives: Modeling analyses for colorectal cancer (CRC) screening focusing solely on the costs of screening do not fully capture the value of screening programs. We evaluated the clinical and economic effects of CRC stool-based screening tests, including impacts on cancer-related outcomes. Methods: A cohort-based decision-analytic costestimator model estimated outcomes for a single round of screening with next-generation multi-target stool DNA (ng mt-sDNA) test or fecal immunochemical test (FIT) from a US payer perspective. Undiagnosed cancers were assumed to become symptomatic (and detected) within 10 years. Clinical assumptions, advanced precancerous lesion and CRC prevalence, and test performance inputs were from clinical trial data. Adherence rates for initial screening and follow-up colonoscopy after a positive result were from realworld data. Input costs included the screening tests, follow-up colonoscopy (with and without polypectomy), and CRC treatment. Results: Compared with FIT, more individuals completed ng mt-sDNA (321,000 vs. 713,000, respectively), leading to the detection of more CRC cases (436 with FIT vs. 2235 with ng mt-sDNA), more advanced precancerous lesions, and more CRC at earlier stages. The cost of screening per patient screened was USD 801 for ng mt-sDNA and USD 124 for FIT. Follow-up colonoscopy cost was USD 149 million with ng mt-sDNA versus USD 22 million with FIT, whereas CRC treatment costs were lower for ng mt-sDNA (USD 1423 million versus USD 1474 million, respectively) . When accounting for both direct and CRC averted costs, the total cost of screening and treatment was USD 1383 million with ng mt-sDNA versus USD 1427 million with FIT. Conclusions: Higher screening costs with ng mt-sDNA versus FIT are counterbalanced by savings realized from enhanced CRC prevention and earlier detection due to the superior test performance and better adherence with ng mt-sDNA.  \nKeywords: colorectal cancer; cost; screening; stool test; adherence; sensitivity; specificity  \n1. Introduction  \nColorectal cancer (CRC) is the third most commonly diagnosed cancer and the second leading cause of cancer-related deaths in the United States, accounting for an estimated  \n154,000 new cases and 52,900 deaths in 2025 [1] . Despite being largely preventable through screening and removal of precancerous lesions, CRC continues to impose a substantial public health burden. Screening enables both early detection and cancer prevention by identifying advanced precancerous lesions (APLs) and early stage malignancies when curative treatment is more likely [2] .  \nThe U.S. Preventive Services Task Force (USPSTF) recommends multiple CRC screening strategies for average-risk adults, including colonoscopy every 10 years, annual fecal immunochemical testing (FIT), and triennial stool DNA–b","cbCaijHow7U1LFoF","https://ap.wps.com/l/cbCaijHow7U1LFoF","pdf",374646,11,"English","# Introduction\n# Materials and Methods\n## Model Overview","[{\"question\":\"Why is value of CRC screening beyond cost important in this analysis?\",\"answer\":\"The study addresses that cost-only modeling does not capture the full value of screening programs, including clinical and economic effects on cancer-related outcomes.\"},{\"question\":\"What compares the two stool-based tests in the model?\",\"answer\":\"The model simulates one screening round for average-risk individuals using ng mt-sDNA or FIT from a US payer perspective, estimating detection and prevention effects alongside costs.\"},{\"question\":\"How does the analysis handle real-world screening behavior?\",\"answer\":\"Adherence for initial screening and follow-up colonoscopy after a positive result comes from real-world data, rather than assuming ideal uptake.\"}]","Value of Stool-Based Colorectal Cancer Screening - Integrating Real-World Adherence, Detection, and Prevention in a Cohort-Based Modeling Analysis | PDF",1790761526,28]