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Molecular subtyping has improved biological classification, but sequencing-based workflows are not always available before treatment or at the population scale. We developed a survival-informed computed tomography (CT) phenotyping framework that combines CT foundation-model representations with PyRadiomics descriptors of tumor shape, intensity, and texture. Across 4 nonoverlapping cohorts, including SYSU6H cohort 1 (\n                    <jats:italic toggle=\"yes\">N<\/jats:italic>\n                    = 902), SYSU6H cohort 2 (\n                    <jats:italic toggle=\"yes\">N<\/jats:italic>\n                    = 3,267), external Ningbo cohort 1 (\n                    <jats:italic toggle=\"yes\">N<\/jats:italic>\n                    = 509), and SYSU6HNAT neoadjuvant-treatment cohort (\n                    <jats:italic toggle=\"yes\">N<\/jats:italic>\n                    = 709), fused CT features were selected and integrated to derive survival-informed CT imaging phenotypes, followed by evaluation of survival, adjusted prognostic associations, molecular correlates, phenotype assignment, and treatment response. The fused representation identified 2 survival-informed imaging phenotypes with marked survival differences. Compared with CT-S1, CT-S2 was associated with worse disease-free survival and overall survival (disease-free survival hazard ratio = 11.16, 95% confidence interval 9.19 to 13.55; overall survival hazard ratio = 14.29, 95% confidence interval 10.83 to 18.85; both\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    &lt; 0.0001) and remained associated with outcomes after adjustment for clinicopathologic variables and measured tumor size. CT-S2 was enriched for consensus molecular subtype 4-like composition and stromal\/extracellular matrix programs, suggesting transcriptomic and microenvironment-associated correlates linked to the adverse imaging phenotype. A flexible phenotype-assignment model reproduced prognostic separation in internal and external cohorts, and assigned phenotypes were associated with survival and pathological response in SYSU6HNAT. These findings suggest that integrated CT phenotyping may provide a noninvasive approach for identifying survival-informed colorectal cancer imaging phenotypes with exploratory molecular correlates, supporting further independent validation.\n                  <\/jats:p>","DOI":"10.34133\/research.1435","type":"journal-article","created":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T02:38:32Z","timestamp":1787884712000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark_01","source":"Crossref","is-referenced-by-count":0,"title":["Integrated CT Foundation Model and Radiomic Features Define Clinically and Biologically Distinct Colorectal Cancer Subtypes"],"prefix":"10.34133","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8894-7973","authenticated-orcid":false,"given":"Du","family":"Cai","sequence":"first","affiliation":[{"name":"Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, \rSun Yat-sen University, Guangzhou, P. R. China."},{"name":"Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, \rSun Yat-sen University, Guangzhou, P. R. China."},{"name":"Biomedical Innovation Center, The Sixth Affiliated Hospital, \rSun Yat-sen University, Guangzhou, P. R. China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoning","family":"Qi","sequence":"additional","affiliation":[{"name":"Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, \rSun Yat-sen University, Guangzhou, P. R. China."},{"name":"Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, \rSun Yat-sen University, Guangzhou, P. R. China."},{"name":"Biomedical Innovation Center, The Sixth Affiliated Hospital, \rSun Yat-sen University, Guangzhou, P. R. China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiuxia","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Radiology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, \rSun Yat-sen University Cancer Center, Guangzhou 510060, P. R. China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yibin","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Colorectal Surgery, \rNingbo Medical Center Lihuili Hospital (Affiliated Lihuili Hospital of Ningbo University), Ningbo 315000, P. R. China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenghang","family":"Li","sequence":"additional","affiliation":[{"name":"Artificial Intelligence Thrust, \rThe Hong Kong University of Science and Technology, Guangzhou, P. R. China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuling","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, \rSun Yat-sen University, Guangzhou, P. R. China."},{"name":"Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, \rSun Yat-sen University, Guangzhou, P. R. China."},{"name":"Biomedical Innovation Center, The Sixth Affiliated Hospital, \rSun Yat-sen University, Guangzhou, P. R. China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinmeng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, \rThe First Hospital of Jilin University, Changchun, P. R. China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rende","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, \rSun Yat-sen University, Guangzhou, P. R. China."},{"name":"Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, \rSun Yat-sen University, Guangzhou, P. R. China."},{"name":"Biomedical Innovation Center, The Sixth Affiliated Hospital, \rSun Yat-sen University, Guangzhou, P. R. China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjun","family":"Mao","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, The Affiliated Wuxi People\u2019s Hospital of Nanjing Medical University, Wuxi People\u2019s Hospital, Wuxi Medical Center, \rNanjing Medical University, Wuxi 214023, P. R. China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojian","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, \rSun Yat-sen University, Guangzhou, P. R. China."},{"name":"Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, \rSun Yat-sen University, Guangzhou, P. R. China."},{"name":"Biomedical Innovation Center, The Sixth Affiliated Hospital, \rSun Yat-sen University, Guangzhou, P. R. China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yize","family":"Mao","sequence":"additional","affiliation":[{"name":"Department of Pancreatobiliary Surgery, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, \rSun Yat-sen University Cancer Center, Guangzhou 510060, P. R. 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