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The current gold standard of combined pathological and molecular profiling is costly, hampering implementation. Here we developed HECTOR (histopathology-based endometrial cancer tailored outcome risk), a multimodal deep learning prognostic model using hematoxylin and eosin-stained, whole-slide images and tumor stage as input, on 2,072 patients from eight EC cohorts including the PORTEC-1\/-2\/-3 randomized trials. HECTOR demonstrated C-indices in internal (<jats:italic>n<\/jats:italic>\u2009=\u2009353) and two external (<jats:italic>n<\/jats:italic>\u2009=\u2009160 and<jats:italic>n<\/jats:italic>\u2009=\u2009151) test sets of 0.789, 0.828 and 0.815, respectively, outperforming the current gold standard, and identified patients with markedly different outcomes (10-year distant recurrence-free probabilities of 97.0%, 77.7% and 58.1% for HECTOR low-, intermediate- and high-risk groups, respectively, by Kaplan\u2013Meier analysis). HECTOR also predicted adjuvant chemotherapy benefit better than current methods. Morphological and genomic feature extraction identified correlates of HECTOR risk groups, some with therapeutic potential. HECTOR improves on the current gold standard and may help delivery of personalized treatment in EC.<\/jats:p>","DOI":"10.1038\/s41591-024-02993-w","type":"journal-article","created":{"date-parts":[[2024,5,24]],"date-time":"2024-05-24T10:01:31Z","timestamp":1716544891000},"page":"1962-1973","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":109,"title":["Prediction of recurrence risk in endometrial cancer with multimodal deep learning"],"prefix":"10.1038","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8195-5735","authenticated-orcid":false,"given":"Sarah","family":"Volinsky-Fremond","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8581-4753","authenticated-orcid":false,"given":"Nanda","family":"Horeweg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonali","family":"Andani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7811-0280","authenticated-orcid":false,"given":"Jurriaan","family":"Barkey Wolf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maxime W.","family":"Lafarge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cor D.","family":"de Kroon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gitte","family":"\u00d8rtoft","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Estrid","family":"H\u00f8gdall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8666-3731","authenticated-orcid":false,"given":"Jouke","family":"Dijkstra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan J.","family":"Jobsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ludy C. 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N.H. declares having received research grants from the DCS and Varian (paid to the institution) unrelated to the present study. C.D.d.K. declares KWF and ZonMW grants unrelated to the project. A.L. received funded research unrelated to the present study from AZ, Clovis, GSK, MSD, Ability, Zentalis, Agenus, Lovance, Sanofi, Roche, OSEimmuno and BMS, is an advisory board member or consultant for AZ, Clovis, GSK, MSD, Merck Serono, Ability, Zentalis, Agenus and Blueprint, and received honoraria and compensation for expenses from AZ, Clovis and GSK. R.A.N. declared research grants unrelated to the present study to the institution from Elekta, Varian, Accuray and Sensius, and is an advisory board member of MSD. M.d.B. received grants from the DCS, the European Research Council, Health Holland, Mendus, BioNovion, Aduro Biotech, Vicinivax, Genmab and IMMIOS (all paid to the institute) unrelated to the present study, received nonfinancial support from BioNTech, Surflay Nanotec and Merck Sharp & Dohme, and is a stock option holder in Sairopa. D.C. is on an advisory board of MSD, received research funding unrelated to the project of HalioDx and Veracyte (to TransSCOT consortium), is a spouse of an Amgen employee, is affiliated to the Wellcome Centre for Human Genetics and National Institute for Health and Care Research (NIHR) Oxford Biomedical Research Centre (BRC), and received funding from Oxford NIHR Comprehensive BRC and a Cancer Research UK (CRUK) Advanced Clinician Scientist Fellowship (C26642\/A27963). C.L.C. received grants from the DCS for the PORTEC-1,-2,-3,-4a, RAINBO trials and research grant for translational work on PORTEC unrelated to the present study, and has leadership roles in and is chair of GCIG Endometrial Cancer Committee. V.H.K. declared being an invited speaker for Sharing Progress in Cancer Care and Indica Labs, is on the advisory board of Takeda and sponsored research agreements with Roche and IAG, all unrelated to the present study. T.B. received grants unrelated to this work by the DCS. The other authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}