{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T06:10:59Z","timestamp":1781849459635,"version":"3.54.5"},"reference-count":24,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T00:00:00Z","timestamp":1765238400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background\/Objectives: Although the binarism between type I and II endometrial cancer was dismissed and substituted with molecular classification, histopathological features remain of paramount importance. Hence, analysing survival outcomes according to histological type, our aim is to clarify whether the morphological features of the tumour retain prognostic relevance in the context of advanced disease. Methods: This is a retrospective analysis led within the Thames Valley Cancer Alliance Network. Results: We include 148 FIGO 2009 stage III\u2013IV patients affected by endometrioid endometrial cancer (EEC) G1, G2, and G3, carcinosarcoma (CS), serous carcinoma (SC), and clear cell carcinoma (CCC) of the uterus. Five year overall survival (OS) is distinct among the histological groups (p-value &lt; 0.001), being 73.3% for G2 endometrioid, 49.2% for G3 endometrioid, 8.3% for CS, and 28.4% for SC. The divergence was marked also for 5 year progression-free survival (PFS) (p-value &lt; 0.001) as follows: for G2 endometrioid, was 76.4%; for G3 endometrioid, 52.7%; and for carcinosarcoma, 5.9%. PFS after 18 months for serous carcinoma was 5.7%. The multivariate analysis found G3 endometrioid (HR 2.91, 95% CI 1.20\u20137.11, p-value 0.018), carcinosarcoma (HR 12.15, 95% CI 5.07\u201329.11, p-value &lt; 0.001), and serous carcinoma (HR 4.84, 95% CI 2.16\u201310.83, p-value &lt; 0.001) as independent predictors of poor survival, as well as cervical invasion (HR 1.83, 95% CI 1.10\u20133.05, p-value 0.020) as the only histopathological feature confirmed. Regarding progression-free only carcinosarcoma (HR 14.91, 95% CI 5.28\u201341.11) and serous carcinoma (HR 17.68, 95% CI 6.41\u201348.75) were associated with an increased risk of recurrence. Conclusions: Our findings testify that, beyond the disease stage, histological subtype remains a major determinant of survival outcome. Cervical involvement is associated with a more aggressive disease, possibly correlated to death beyond relapse. Prospective trials involving advanced stage endometrial cancer, stratified by histological subtype and integrated with the molecular classification, are required.<\/jats:p>","DOI":"10.3390\/jcm14248726","type":"journal-article","created":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T16:11:18Z","timestamp":1765383078000},"page":"8726","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Insights from the Pre-Molecular Era in Advanced Endometrial Cancer: Benchmarking Prognostic Indicators in High-Risk Tumours"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-2831-2134","authenticated-orcid":false,"given":"Jacopo","family":"Conforti","sequence":"first","affiliation":[{"name":"Department of Gynaecology Oncology, Churchill Hospital, Oxford University Hospitals, National Health Service (NHS) Foundation Trust, Oxford OX3 7LE, UK"},{"name":"Department of Clinical and Experimental Sciences, University of Brescia, 25136 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-1228-1602","authenticated-orcid":false,"given":"Sabina Ioana","family":"Nistor","sequence":"additional","affiliation":[{"name":"Department of Gynaecology Oncology, Churchill Hospital, Oxford University Hospitals, National Health Service (NHS) Foundation Trust, Oxford OX3 7LE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2818-0966","authenticated-orcid":false,"given":"Negin","family":"Sadeghi","sequence":"additional","affiliation":[{"name":"Nuffield Department of Women\u2019s and Reproductive Health, University of Oxford, Oxford OX2 6GG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1926-5397","authenticated-orcid":false,"given":"Andreas","family":"Zouridis","sequence":"additional","affiliation":[{"name":"Nuffield Department of Women\u2019s and Reproductive Health, University of Oxford, Oxford OX2 6GG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ammara","family":"Kashif","sequence":"additional","affiliation":[{"name":"Nuffield Department of Women\u2019s and Reproductive Health, University of Oxford, Oxford OX2 6GG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7562-3534","authenticated-orcid":false,"given":"Ahmed","family":"Darwish","sequence":"additional","affiliation":[{"name":"Nuffield Department of Women\u2019s and Reproductive Health, University of Oxford, Oxford OX2 6GG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7407-8247","authenticated-orcid":false,"given":"Sarah Louise","family":"Smyth","sequence":"additional","affiliation":[{"name":"Wexham Park Hospital, Frimley Health NHS Foundation Trust, Slough SL2 4HL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7216-3560","authenticated-orcid":false,"given":"Alisha","family":"Sattar","sequence":"additional","affiliation":[{"name":"Nuffield Department of Women\u2019s and Reproductive Health, University of Oxford, Oxford OX2 6GG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8272-8537","authenticated-orcid":false,"given":"Susan","family":"Addley","sequence":"additional","affiliation":[{"name":"University Hospital of Derby and Burton NHS Foundation Trust, Derby DE2 3NE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2801-2786","authenticated-orcid":false,"given":"Christina","family":"Pappa","sequence":"additional","affiliation":[{"name":"Nuffield Department of Women\u2019s and Reproductive Health, University of Oxford, Oxford OX2 6GG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Damato","sequence":"additional","affiliation":[{"name":"Department of Histopathology, Oxford University Hospitals NHS Foundation Trust, Oxford OX3 9DU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4901-1929","authenticated-orcid":false,"given":"Mostafa","family":"Abdalla","sequence":"additional","affiliation":[{"name":"Guy\u2019s and St Thomas\u2019 NHS Foundation Trust, London SE1 9RT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean","family":"Kehoe","sequence":"additional","affiliation":[{"name":"Department of Gynaecology Oncology, Churchill Hospital, Oxford University Hospitals, National Health Service (NHS) Foundation Trust, Oxford OX3 7LE, UK"},{"name":"Nuffield Department of Women\u2019s and Reproductive Health, University of Oxford, Oxford OX2 6GG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4388-0082","authenticated-orcid":false,"given":"Andrea","family":"Giannini","sequence":"additional","affiliation":[{"name":"Unit of Gynecology, Department of Surgical and Medical Sciences and Translational Medicine, Sant\u2019Andrea Hospital, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7065-2432","authenticated-orcid":false,"given":"Federico","family":"Ferrari","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Sciences, University of Brescia, 25136 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3293-5321","authenticated-orcid":false,"given":"Hooman","family":"Soleymani Majd","sequence":"additional","affiliation":[{"name":"Department of Gynaecology Oncology, Churchill Hospital, Oxford University Hospitals, National Health Service (NHS) Foundation Trust, Oxford OX3 7LE, UK"},{"name":"Nuffield Department of Women\u2019s and Reproductive Health, University of Oxford, Oxford OX2 6GG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,9]]},"reference":[{"key":"ref_1","unstructured":"World Cancer Research Fund (2025, October 19). 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