Endometrial Cancer · Radiation · Adjuvant / Postoperative · Evidence cut-off 26 Oct 2026

PORTEC-4a

Can molecular-profile-directed adjuvant treatment reduce overtreatment after surgery while remaining non-inferior for vaginal recurrence?

One underlying study; aliases and follow-up reports consolidated. Primary discipline: Radiation.

Population and eligibility

564 eligible/evaluable patients with high-intermediate-risk endometrial cancer after surgery.

Postoperative high-intermediate-risk endometrial cancer stratified by molecular profile including POLE, MMR, NSMP and p53-abnormal status.

Sample size

564 randomised/evaluable as reported.

Intervention

Profile-directed strategy: observation for favourable profile, vaginal brachytherapy for intermediate profile, pelvic RT for unfavourable profile.

Comparator

Standard vaginal brachytherapy.

Endpoints and results

Primary cumulative vaginal recurrence; prespecified non-inferiority margin 7 percentage points.

5-year vaginal recurrence 4.5% vs 1.6%. HR 2.71 (95% CI 0.79–9.34); upper one-sided confidence bound for absolute difference 5.3%, below 7% margin; p for non-inferiority=0.005.
46% in the molecular-profile group had favourable profiles and were spared adjuvant treatment.
Grade ≥3 treatment-related GU toxicity ~1% vs 2%.

Absolute Effect and outcome visualisation

5-year vaginal recurrence

% with vaginal recurrence by 5 years · 5 years. Bars show source-reported fixed-time percentages.

Molecular strategy

4.5%

Standard brachytherapy

1.6%

Interpretation: Non-inferiority, not superiority. No NNT for superiority. Show the numerically higher recurrence with the treatment-sparing strategy and its prespecified margin.

Toxicity, discontinuation and quality of life

Trial-specific harms: Grade ≥3 GU toxicity ~1% vs 2%; treatment exposure varies by molecular risk group.

Treatment burden/discontinuation: 46% with favourable profile spared adjuvant treatment, reducing radiation visits and exposure.

Quality of life: No numeric QoL difference asserted; reduced treatment exposure is a key patient-centred consideration.

Subgroups, maturity and limitations

Subgroups: Show outcomes by molecular profile from the primary paper; biology and treatment differ by group.

Maturity: Five-year recurrence analysis published in 2026.

Limitations: Wide HR CI and numerically higher recurrence in the molecular strategy arm; non-inferiority does not mean identical risk.

Clinical interpretation

PORTEC-4a supports molecular risk-adapted postoperative treatment that spares adjuvant therapy in a substantial favourable-risk subgroup while meeting its non-inferiority criterion.

Use current regional guidelines, patient fitness, biomarkers, competing risks, alternatives and regulatory status before clinical application. Clinical freshness review and browser-rendered QA remain pending.

Primary sources and registry

Registry: NCT03469674

The Absolute Effect · Updated 26 October 2026 · Never derive NNT from median survival.