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Volume 14
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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

Insights from the Pre-Molecular Era in Advanced Endometrial Cancer: Benchmarking Prognostic Indicators in High-Risk Tumours

by
Jacopo Conforti
1,2,
Sabina Ioana Nistor
1,
Negin Sadeghi
3,
Andreas Zouridis
3,
Ammara Kashif
3,
Ahmed Darwish
3,
Sarah Louise Smyth
4,
Alisha Sattar
3,
Susan Addley
5,
Christina Pappa
3,
Stephen Damato
6,
Mostafa Abdalla
7,
Sean Kehoe
1,3,
Andrea Giannini
8,
Federico Ferrari
2 and
Hooman Soleymani Majd
1,3,*
1
Department of Gynaecology Oncology, Churchill Hospital, Oxford University Hospitals, National Health Service (NHS) Foundation Trust, Oxford OX3 7LE, UK
2
Department of Clinical and Experimental Sciences, University of Brescia, 25136 Brescia, Italy
3
Nuffield Department of Women’s and Reproductive Health, University of Oxford, Oxford OX2 6GG, UK
4
Wexham Park Hospital, Frimley Health NHS Foundation Trust, Slough SL2 4HL, UK
5
University Hospital of Derby and Burton NHS Foundation Trust, Derby DE2 3NE, UK
6
Department of Histopathology, Oxford University Hospitals NHS Foundation Trust, Oxford OX3 9DU, UK
7
Guy’s and St Thomas’ NHS Foundation Trust, London SE1 9RT, UK
8
Unit of Gynecology, Department of Surgical and Medical Sciences and Translational Medicine, Sant’Andrea Hospital, Sapienza University of Rome, 00185 Rome, Italy
*
Author to whom correspondence should be addressed.
J. Clin. Med. 2025, 14(24), 8726; https://doi.org/10.3390/jcm14248726 (registering DOI)
Submission received: 9 November 2025 / Revised: 26 November 2025 / Accepted: 8 December 2025 / Published: 9 December 2025
(This article belongs to the Special Issue Risk Prediction for Gynecological Cancer)
Versions Notes

Abstract

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–IV 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 < 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 < 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 1.20–7.11, p-value 0.018), carcinosarcoma (HR 12.15, 95% CI 5.07–29.11, p-value < 0.001), and serous carcinoma (HR 4.84, 95% CI 2.16–10.83, p-value < 0.001) as independent predictors of poor survival, as well as cervical invasion (HR 1.83, 95% CI 1.10–3.05, p-value 0.020) as the only histopathological feature confirmed. Regarding progression-free only carcinosarcoma (HR 14.91, 95% CI 5.28–41.11) and serous carcinoma (HR 17.68, 95% CI 6.41–48.75) 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.
Keywords: endometrial cancer; advance stage; endometrioid endometrial cancer; carcinosarcoma; serous carcinoma; clear cell carcinoma; molecular mutation endometrial cancer; advance stage; endometrioid endometrial cancer; carcinosarcoma; serous carcinoma; clear cell carcinoma; molecular mutation

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MDPI and ACS Style

Conforti, J.; Nistor, S.I.; Sadeghi, N.; Zouridis, A.; Kashif, A.; Darwish, A.; Smyth, S.L.; Sattar, A.; Addley, S.; Pappa, C.; et al. Insights from the Pre-Molecular Era in Advanced Endometrial Cancer: Benchmarking Prognostic Indicators in High-Risk Tumours. J. Clin. Med. 2025, 14, 8726. https://doi.org/10.3390/jcm14248726

AMA Style

Conforti J, Nistor SI, Sadeghi N, Zouridis A, Kashif A, Darwish A, Smyth SL, Sattar A, Addley S, Pappa C, et al. Insights from the Pre-Molecular Era in Advanced Endometrial Cancer: Benchmarking Prognostic Indicators in High-Risk Tumours. Journal of Clinical Medicine. 2025; 14(24):8726. https://doi.org/10.3390/jcm14248726

Chicago/Turabian Style

Conforti, Jacopo, Sabina Ioana Nistor, Negin Sadeghi, Andreas Zouridis, Ammara Kashif, Ahmed Darwish, Sarah Louise Smyth, Alisha Sattar, Susan Addley, Christina Pappa, and et al. 2025. "Insights from the Pre-Molecular Era in Advanced Endometrial Cancer: Benchmarking Prognostic Indicators in High-Risk Tumours" Journal of Clinical Medicine 14, no. 24: 8726. https://doi.org/10.3390/jcm14248726

APA Style

Conforti, J., Nistor, S. I., Sadeghi, N., Zouridis, A., Kashif, A., Darwish, A., Smyth, S. L., Sattar, A., Addley, S., Pappa, C., Damato, S., Abdalla, M., Kehoe, S., Giannini, A., Ferrari, F., & Soleymani Majd, H. (2025). Insights from the Pre-Molecular Era in Advanced Endometrial Cancer: Benchmarking Prognostic Indicators in High-Risk Tumours. Journal of Clinical Medicine, 14(24), 8726. https://doi.org/10.3390/jcm14248726

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