Molecular profile-based adjuvant treatment for women with high-intermediate risk endometrial cancer (PORTEC‑4a)

Cancer research · Endometrial cancer

Individualised adjuvant treatment by molecular integrated risk profile is safe and effective for patients with high‑intermediate risk endometrial cancer; it spared 46 % of patients with a favourable profile from adjuvant treatment, and reduces both overtreatment and undertreatment.

PORTEC‑4a investigated molecular risk‑profile‑based individualised adjuvant treatment for women with high‑intermediate risk endometrial cancer, aiming to reduce both overtreatment and undertreatment while optimising locoregional control. PORTEC‑4a was a randomised, open‑label, phase 3, multicentre, non‑inferiority trial. Women (≥18 years, WHO performance score 0–2) with early‑stage high‑intermediate risk endometrial cancer were eligible. Patients were randomly assigned post‑surgery in a 2:1 ratio to either adjuvant treatment according to their integrated risk profile or to standard vaginal brachytherapy. Adjuvant treatment in the molecular‑profile group depended on the profile: observation for favourable (POLE‑mutated or NSMP‑CTNNB1 wt), brachytherapy for intermediate (MMRd or NSMP‑CTNNB1 mut) and pelvic radiotherapy for unfavourable (p53 abnormal or extensive LVSI or L1CAM overexpression). The primary endpoint was the 5‑year cumulative incidence of vaginal recurrence as first event. The 5‑year cumulative incidence of vaginal recurrence was 4.75 % in the molecular‑profile group versus 1.76 % in the standard group (HR 2.71 [95 % CI 0.79–9.74]). The difference (5.73 %) was below the predefined equivalence margin of 7.70 % (p_non‑inferiority = 0.0005). Secondary analyses in patients with favourable profiles showed 5‑year recurrence of 4.71 % versus 0.79 % (HR 3.79 [0.48–32.95]). Grade 3+ toxicities were similar between groups. Individualised adjuvant treatment was safe and effective, sparing 46 % of patients with favourable profiles from treatment and reducing both overtreatment and undertreatment.

In high‑intermediate risk endometrial cancer, personalised adjuvant therapy guided by molecular profiling can prevent unnecessary treatment while maintaining locoregional control, improving patient outcomes and quality of life.

Evidence level: Számítógépes vagy elméleti. Modellből vagy adatbányászatból származó jel.

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