Toxicity, health-related quality of life and sexuality after molecular profile-based adjuvant treatment in high-intermediate risk endometrial cancer, PORTEC-4a

PORTEC-4a was the first to incorporate molecular-integrated profile-guided adjuvant treatment in early-stage high-intermediate-risk endometrial cancer (EC), demonstrating non-inferiority. Here, adverse events (AE), health-related quality of life (HRQoL) and sexual health are reported. 564 patients were randomised to molecular-based adjuvant treatment ( n = 367) or standard vaginal brachytherapy (VBT, n = 197). In the molecular-profile arm, patients underwent observation, VBT or pelvic radiotherapy according to molecular-integrated profile. HRQoL and sexual functioning were assessed with EORTC QLQ-C30 and EN24 modules and compared with age-matched normative data. Median follow-up was 58.1 months; 523 (92.7%) patients were evaluable. Grade 1–2 AEs were less frequent in the molecular-profile arm at treatment completion compared with the standard arm (28.3% vs. 45.2%, p < 0.01), without differences in grade 3–4 AEs ( p = 0.46). Throughout follow-up, treatment-related grade 3–4 AEs were rare (1% vs. 2%). HRQoL remained comparable to normative data over time. Sexual interest/activity was similar between arms, but lower than normative values. 75.5% of patients reported ≥1 reason for sexual inactivity; disease-related sexual inactivity decreased from 24.2% to 9.2% at 3 years. Molecular-guided adjuvant treatment for patients with high-intermediate riskEC is associated with low toxicity, preserved HRQoL and slightly reduced sexual activity due to personal factors (no partner, sex not important in their relationship or partner-related medical issues) rather than their own illness.

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Publication Details

Journal
British Journal of Cancer
Published
2026-11-11
DOI
https://doi.org/10.1038/s41416-026-03642-4
Primary Topic
Endometrial and Cervical Cancer Treatments
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article
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article

Toxicity, health-related quality of life and sexuality after molecular profile-based adjuvant treatment in high-intermediate risk endometrial cancer, PORTEC-4a

Katrien Vandecasteele, Anne Sophie V M van den Heerik, Jannet C. Beukema, Remi A. Nout et al.
British Journal of Cancer
Endometrial and Cervical Cancer Treatments
article

Toxicity, health-related quality of life and sexuality after molecular profile-based adjuvant treatment in high-intermediate risk endometrial cancer, PORTEC-4a

Katrien Vandecasteele, Anne Sophie V M van den Heerik, Jannet C. Beukema, Remi A. Nout, Karen W. Verhoeven-Adema, Cathalijne Post, Stephanie M. de Boer, Dorine S.J. Tseng, Charles Gillham, Stefan Kommoss, Hans W. Nijman, Jan Willem Mens, Jeltsje S. Cnossen, Filip Frühauf, Marie A.D. Haverkort, Cyrus Chargari, Hein Putter, Carien L. Creutzberg, Nanda Horeweg, Bastiaan G. Wortman, Vincent T.H.B.M. Smit, Henrike G. Westerveld, Friederike L.A. Koppe, Marlies E. Nowee, Nienke Kuijsters, Maria A.A. de Jong
article en

Abstract

PORTEC-4a was the first to incorporate molecular-integrated profile-guided adjuvant treatment in early-stage high-intermediate-risk endometrial cancer (EC), demonstrating non-inferiority. Here, adverse events (AE), health-related quality of life (HRQoL) and sexual health are reported. 564 patients were randomised to molecular-based adjuvant treatment ( n = 367) or standard vaginal brachytherapy (VBT, n = 197). In the molecular-profile arm, patients underwent observation, VBT or pelvic radiotherapy according to molecular-integrated profile. HRQoL and sexual functioning were assessed with EORTC QLQ-C30 and EN24 modules and compared with age-matched normative data. Median follow-up was 58.1 months; 523 (92.7%) patients were evaluable. Grade 1–2 AEs were less frequent in the molecular-profile arm at treatment completion compared with the standard arm (28.3% vs. 45.2%, p < 0.01), without differences in grade 3–4 AEs ( p = 0.46). Throughout follow-up, treatment-related grade 3–4 AEs were rare (1% vs. 2%). HRQoL remained comparable to normative data over time. Sexual interest/activity was similar between arms, but lower than normative values. 75.5% of patients reported ≥1 reason for sexual inactivity; disease-related sexual inactivity decreased from 24.2% to 9.2% at 3 years. Molecular-guided adjuvant treatment for patients with high-intermediate riskEC is associated with low toxicity, preserved HRQoL and slightly reduced sexual activity due to personal factors (no partner, sex not important in their relationship or partner-related medical issues) rather than their own illness.

British Journal of Cancer
University Medical Center Groningen (NL), Charles University (CZ), Leiden University Medical Center (NL), Ghent University Hospital (BE), Catharina Ziekenhuis (NL), Institut Gustave Roussy (FR), Erasmus MC (NL), The Netherlands Cancer Institute (NL), University Medical Center Utrecht (NL), Cancer Trials Ireland (IE), St. Luke's Hospital (IE), University Children's Hospital Tübingen (DE), Instituut Verbeeten (NL), Netherlands Comprehensive Cancer Organisation (NL), Radiotherapiegroep (NL), Erasmus MC Cancer Institute (NL), Amsterdam University Medical Centers (NL), Radiotherapeutisch Instituut Friesland (NL), General University Hospital in Prague (CZ), University of Amsterdam (NL)
Endometrial and Cervical Cancer Treatments
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