Background
Phase III RCT (PORTEC-2). 427 patients with high-intermediate risk (HIR) stage I-IIA endometrial carcinoma after TAH-BSO (lymph node dissection not required). HIR defined as: age ≥60 with grade 1–2 and deep myometrial invasion or LVSI; any age with grade 3 and <50% myometrial invasion. Randomized to pelvic EBRT (46 Gy in 23 fractions) vs vaginal brachytherapy (VBT) alone (HDR: 3 fractions of 7 Gy or 5 fractions of 5.6 Gy; or LDR equivalent). Designed to test VBT non-inferiority to EBRT for vaginal recurrence control with better QoL. Long-term 10-year update published (Wortman Br J Cancer 2018).
Interventions and follow up
Arm A: Pelvic EBRT 46 Gy in 23 fractio
Arm B: Vaginal brachytherapy (VBT) alone — HDR 3×7 Gy or 5×5.6 Gy or LDR equivalent
Primary endpoint: Vaginal recurrence (non-inferiority)
mFollow up: 45 months (primary); 10 years (Wortman 2018)
Arm B: Vaginal brachytherapy (VBT) alone — HDR 3×7 Gy or 5×5.6 Gy or LDR equivalent
Primary endpoint: Vaginal recurrence (non-inferiority)
mFollow up: 45 months (primary); 10 years (Wortman 2018)
Results
5-year vaginal recurrence: 1.8% (EBRT) vs 1.8% (VBT) — non-inferiority confirmed, P=.74
5-year locoregional recurrence: 2.1% (EBRT) vs 5.1% (VBT), P=.17 — NS (mostly pelvic node failures)
5-year distant metastasis: 8.3% (EBRT) vs 5.7% (VBT) — NS
5-year OS: 84.8% (EBRT) vs 85.3% (VBT) — equivalent
10-year vaginal recurrence: 2.0% vs 3.2% — maintained equivalence
5-year locoregional recurrence: 2.1% (EBRT) vs 5.1% (VBT), P=.17 — NS (mostly pelvic node failures)
5-year distant metastasis: 8.3% (EBRT) vs 5.7% (VBT) — NS
5-year OS: 84.8% (EBRT) vs 85.3% (VBT) — equivalent
10-year vaginal recurrence: 2.0% vs 3.2% — maintained equivalence
Adverse events
Main adverse events: Acute grade 1–2 bowel toxicity: 53.8% (EBRT) vs 12.6% (VBT), P<.001. Grade ≥2 late bowel toxicity: significantly higher with EBRT. Patient-reported QoL (diarrhea, fecal leakage): significantly worse with EBRT. Urinary toxicity: higher with EBRT. Vaginal toxicity slightly higher with VBT (brachytherapy-related).
Conclusions
VBT is non-inferior to pelvic EBRT for vaginal recurrence control in high-intermediate risk endometrial cancer, with significantly better bowel toxicity and quality of life, establishing VBT as the preferred adjuvant treatment over EBRT for this risk group.
Key Limitations
Key Limitations: No lymph node dissection required — some patients had occult nodal disease (partially explaining the higher pelvic recurrence rate with VBT: 3% vs 0.4%). The non-inferiority margin for vaginal recurrence was generous (5%). No chemotherapy arm — the role of adjuvant chemotherapy in HIR disease was not addressed (GOG 249 addressed this). Predates molecular risk stratification — POLE and MMR status were not incorporated.
Clinical Context
PORTEC-2 fundamentally changed practice: VBT is now the standard adjuvant treatment for high-intermediate risk stage I-IIA endometrial cancer at most centers worldwide. Pelvic EBRT is reserved for stage III disease or high-risk histologies (serous, clear cell) per PORTEC-3, GOG 258. Modern PORTEC-4 incorporates molecular risk stratification to further personalize adjuvant therapy.