Adjuvant chemoradiotherapy versus radiotherapy alone in women with high-risk endometrial cancer (PORTEC-3) - 10-year clinical outcomes and post-hoc analysis by molecular classification

Sep 23, 2026

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Adjuvant chemoradiotherapy was evaluated against pelvic radiotherapy alone in the randomized PORTEC-3 phase 3 trial for women with high-risk endometrial cancer. The 10-year analysis assessed overall survival and recurrence-free survival, with additional post-hoc stratification by molecular tumor classification. Among 660 evaluable patients across 103 centers, chemoradiotherapy improved 10-year overall survival and recurrence-free survival versus radiotherapy alone, with the largest clinically relevant benefit in p53-abnormal tumors. Molecular subgroups such as MMRd and POLEmut showed no clear benefit, while NSMP effects varied by oestrogen-receptor status.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages12

Reading Time30 min

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Summary

Background

Methods

Findings

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Funding

Introduction

Articles LancetOncol 2025; 26: 1370–81 Published Online September 5, 2025 [https://doi.org/10.1016/](https://doi.org/10.1016/)[ ](https://doi.org/10.1016/)[S1470-2045](S1470-2045)([25](25))[00379-1](00379-1)[ ](00379-1)Department of Radiation Oncology, Leiden University Medical Centre, Leiden, Netherlands (C C B Post MD, S M de Boer MD, Prof RA Nout MD, Prof C L Creutzberg MD); Department of Clinical Oncology, Barts Health NHS Trust, London, UK (M E Powell MD); Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia (Prof L Mileshkin MD); Department of Surgical Sciences and Gynaecology, Città della Salute and S Anna Hospital, Turin, Italy (Prof D Katsaros MD); Department of Gynaecologic Oncology, University of Sherbrooke, Sherbrooke, QC, Canada (Prof P Bessette MD); Department of Cancer Medicine and Gynaecological Tumours Translational Research Lab, Gustave Roussy Cancer Centre, INSERM U981, Université Paris Saclay, Villejuif, France (A Leary MD); Department of Medical Oncology, Radboudumc, Nijmegen, Netherlands (P B Ottevanger MD); Department of Clinical Oncology, University College Hospital London, London, UK (M McCormack MD); Department of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia (P Khaw MD); Department of Radiation Oncology, Azienda Socio Sanitaria Territoriale, Lecco, Italy (R D’Amico MD); Department of Radiation Adjuvant chemoradiotherapy versus radiotherapy alone in women with high-risk endometrial cancer (PORTEC-3): 10-year clinical outcomes and post-hoc analysis by molecular classification from a randomised phase 3 trial Cathalijne C B Post, Stephanie M de Boer, Melanie E Powell, Linda Mileshkin, Dionyssios Katsaros, Paul Bessette, Alexandra Leary, Petronella B Ottevanger, Mary McCormack, Pearly Khaw, Romerai D’Amico, Anthony Fyles, Cyrus Chargari, Henry C Kitchener, Viet Do, Andrea Lissoni, Diane Provencher, Catherine Genestie, Hans W Nijman, Karen Whitmarsh, Ina MJürgenliemk-Schulz, Amanda Feeney, Ludy C H W Lutgens, Jeanette Bouma, Alicia Leon-Castillo, Remi A Nout, Hein Putter, Tjalling Bosse, Carien L Creutzberg Summary Background The PORTEC-3 trial investigated the benefit of chemoradiotherapy versus pelvic radiotherapy alone for women with high-risk endometrial cancer. We present the preplanned long-term analysis of the randomised PORTEC-3 trial with a post-hoc analysis including molecular classification of the tumours. Methods PORTEC-3 was an open-label, multicentre, randomised, international phase 3 trial. Women were eligible if they had high-risk endometrial cancer (either International Federation of Gynecology and Obstetrics 2009 stage I, grade 3, with deep myometrial invasion and/or lymphovascular space invasion; stage II–III; or stage I–III with serous or clear-cell histology), were aged 18 years or older, and had a WHO performance score of 0–2. Participants were randomly assigned (1:1) to receive pelvic radiotherapy (48·6 Gyin 1·8 Gy fractions) or chemoradiotherapy (radiotherapy combined with two cycles of cisplatin 50 mg/m² intravenously in weeks one and four, followed by four cycles of carboplatin area-under-the-curve 5 and paclitaxel 175 mg/m² intravenously at 3-week intervals) . Randomisation was done by use of biased-coin minimisation with stratification for participating centre, lymphadenectomy, stage, and histological type. We report the primary outcomes of overall survival and recurrence-free survival at 10 years. We also report primary outcomes by molecular subgroup in a post-hoc analysis. Survival was analysed in the intention-to-treat population. The study is [registered with ClinicalTrials.gov](registered with ClinicalTrials.gov) (NCT00411138) and is now complete. Findings Between Nov 23, 2006, and Dec 20, 2013, 660 eligible and evaluable patients recruited at 103 centres in six clinical trial groups across seven countries were randomly assigned to chemoradiotherapy (n=330) or radiotherapy alone

FAQs

What was the main question of the PORTEC-3 trial described in this article?

Whether adjuvant chemoradiotherapy improves outcomes compared with radiotherapy alone for women with high-risk endometrial cancer, with long-term and molecularly informed analyses at 10 years.

How were overall survival and recurrence-free survival assessed at 10 years?

The study reported primary outcomes of overall survival and recurrence-free survival at 10 years, including both intention-to-treat results and post-hoc molecular subgroup analyses.

Which molecular subgroup showed the most clinically relevant benefit from chemoradiotherapy?

p53 abnormal tumors showed the largest clinically relevant improvement, with higher 10-year overall survival and recurrence-free survival versus radiotherapy alone.

Sep 23, 2026

Uploaded by Ben