{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:09:52Z","timestamp":1785409792022,"version":"3.56.0"},"posted":{"date-parts":[[2026,7,14]]},"group-title":"Oncology","reference-count":42,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T00:00:00Z","timestamp":1783987200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Cancer Early Detection Advanced Research Center, Oregon Health and Science University","award":["Full 2024-1960"],"award-info":[{"award-number":["Full 2024-1960"]}]},{"award":["U01 CA253913"],"award-info":[{"award-number":["U01 CA253913"]}],"id":[{"id":"https:\/\/ror.org\/040gcmg81","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,7,14]]},"abstract":"<jats:title>Summary<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Colorectal cancer (CRC) screening strategies such as colonoscopy and fecal immunochemical testing (FIT) reduce CRC mortality through both early detection and prevention via precursor lesion removal. Multicancer early detection (MCED) blood tests offer the potential to detect multiple cancers with a single assay but provide little opportunity for cancer prevention. Whether the ability to detect multiple cancers can offset the loss of CRC prevention remains unclear.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We used microsimulation to compare MCED and guideline-recommended CRC screening strategies. CRC outcomes were simulated using CRC-SPIN v3.0 and non-CRC cancers using MCEDsim, calibrated to SEER incidence data. Assuming optimistic MCED preclinical sensitivity equal to published case-control estimates, we compared life-years gained and late-stage disease outcomes for annual FIT, decennial colonoscopy, and MCED-only strategies across a range of preclinical durations and survival benefit assumptions.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Relative to no screening, colonoscopy and FIT reduced late-stage diagnoses by 26% and 25%, respectively, versus 20%\u201332% for annual MCED screening. Across assumptions, MCED-only strategies generated 33%\u201351% as many life-years gained as colonoscopy.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Currently available MCED tests are unlikely to be effective replacements for guideline-recommended CRC screening, which derives substantial benefit from the detection and removal of precursor lesions. MCED screening may provide additional benefit as a supplement to recommended CRC screening.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.07.10.26357782","type":"posted-content","created":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T16:40:15Z","timestamp":1784047215000},"source":"Crossref","is-referenced-by-count":0,"title":["Should Multi-Cancer Early Detection Testing Replace Guideline-Recommended Colorectal Cancer Screening? A Comparative Modeling Analysis"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-7853-7240","authenticated-orcid":false,"given":"Ishfaq","family":"Ahmad","sequence":"first","affiliation":[{"name":"Cancer Early Detection Advanced Research Center, Oregon Health and Science University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolyn M.","family":"Rutter","sequence":"additional","affiliation":[{"name":"Division of Public Health Sciences, Fred Hutchinson Cancer Center"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris E.","family":"Maerzluft","sequence":"additional","affiliation":[{"name":"Division of Public Health Sciences, Fred Hutchinson Cancer Center"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel","family":"Dengos","sequence":"additional","affiliation":[{"name":"Cancer Early Detection Advanced Research Center, Oregon Health and Science University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kemal C.","family":"Gogebakan","sequence":"additional","affiliation":[{"name":"Division of Public Health Sciences, Fred Hutchinson Cancer Center"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane M.","family":"Lange","sequence":"additional","affiliation":[{"name":"Cancer Early Detection Advanced Research Center, Oregon Health and Science University"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026071701251012000_2026.07.10.26357782v1.1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21772"},{"key":"2026071701251012000_2026.07.10.26357782v1.2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2021.6238"},{"key":"2026071701251012000_2026.07.10.26357782v1.3","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2017.05.013"},{"issue":"10","key":"2026071701251012000_2026.07.10.26357782v1.4","doi-asserted-by":"crossref","first-page":"3024","DOI":"10.1007\/s10620-019-05661-z","article-title":"Low Sensitivity of Fecal Immunochemical Tests (FIT) for Detection of Sessile Serrated Adenomas\/Polyps Confirmed Over Clinical Setting, Geography, and FIT System","volume":"64","year":"2019","journal-title":"Dig Dis Sci"},{"key":"2026071701251012000_2026.07.10.26357782v1.5","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-019-05569-8"},{"issue":"1","key":"2026071701251012000_2026.07.10.26357782v1.6","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.cgh.2010.09.013","article-title":"Prevalence and Variable Detection of Proximal Colon Serrated Polyps During Screening Colonoscopy","volume":"9","year":"2011","journal-title":"Clinical Gastroenterology and Hepatology"},{"issue":"1","key":"2026071701251012000_2026.07.10.26357782v1.7","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1186\/s12876-025-03679-4","article-title":"One in three adenomas could be missed by white-light colonoscopy \u2013 findings from a systematic review and meta-analysis","volume":"25","year":"2025","journal-title":"BMC Gastroenterol"},{"key":"2026071701251012000_2026.07.10.26357782v1.8","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1301969"},{"issue":"20","key":"2026071701251012000_2026.07.10.26357782v1.9","doi-asserted-by":"crossref","first-page":"5953","DOI":"10.7150\/jca.46661","article-title":"Colonoscopic screening is associated with reduced Colorectal Cancer incidence and mortality: a systematic review and meta-analysis","volume":"11","year":"2020","journal-title":"J Cancer"},{"key":"2026071701251012000_2026.07.10.26357782v1.10","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2021.5746"},{"issue":"1","key":"2026071701251012000_2026.07.10.26357782v1.11","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1001\/jama.2025.7515","article-title":"Clinical Validation of a Circulating Tumor DNA\u2013Based Blood Test to Screen for Colorectal Cancer","volume":"334","year":"2025","journal-title":"JAMA"},{"key":"2026071701251012000_2026.07.10.26357782v1.12","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2304714"},{"key":"2026071701251012000_2026.07.10.26357782v1.13","doi-asserted-by":"crossref","unstructured":"Meester RGS , Piscitello AJ , Duimstra JA , Liang PS , Shaukat A , Levin TR . 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Safety and performance results from PATHFINDER 2, a registrational study of a multi-cancer early detection (MCED) test in an intended-use population. J Clin Oncol. 2026 Jun;44(17 suppl). Available from: https:\/\/ascopubs.org\/doi\/10.1200\/JCO.2026.44.17_suppl.LBA10509.","DOI":"10.1200\/JCO.2026.44.17_suppl.LBA10509"},{"key":"2026071701251012000_2026.07.10.26357782v1.17","unstructured":"Diehl F , others. Performance of a Multi-Analyte, Multi-Cancer Early Detection (MCED) Blood Test in a Prospectively Collected Cohort. In: Proceedings of the American Association for Cancer Research (AACR) Annual Meeting 2024. 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