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.