Background
Combined analysis of two independent phase III RCTs: ASTEC (n=905, UK) and NCIC CTG EN.5 (n=334, Canada). Both enrolled patients with stage I-II endometrial carcinoma of any histology after hysterectomy and staged with bilateral salpingo-oophorectomy ± lymphadenectomy. Both randomized to pelvic EBRT (40–46 Gy) vs no EBRT (VBT allowed in both arms per center practice). Combined analysis powered to detect OS difference. ASTEC also had a separate randomization for lymph node dissection (not addressed here).
Interventions and follow up
Arm A: Pelvic EBRT 40–46 Gy (± VBT per center policy)
Arm B: No pelvic EBRT (observation or VBT alone per center policy)
Primary endpoint: Overall survival (combined analysis)
mFollow up: 58 month
Arm B: No pelvic EBRT (observation or VBT alone per center policy)
Primary endpoint: Overall survival (combined analysis)
mFollow up: 58 month
Results
5-year OS: 84% (EBRT) vs 84% (no EBRT), HR 1.05 (95% CI 0.85–1.29) — not significant
5-year recurrence-free survival: 81% vs 79%, HR 0.93 (95% CI 0.73–1.17) — not significant
Locoregional recurrence (including vaginal): 3% (EBRT) vs 7% (no EBRT) — reduced with EBRT
Distant recurrence: Similar between arms
5-year recurrence-free survival: 81% vs 79%, HR 0.93 (95% CI 0.73–1.17) — not significant
Locoregional recurrence (including vaginal): 3% (EBRT) vs 7% (no EBRT) — reduced with EBRT
Distant recurrence: Similar between arms
Adverse events
Main adverse events: Acute and late bowel toxicity significantly higher in EBRT arm. Late bowel toxicity grade 3+: 3% (EBRT) vs 1% (no EBRT). Urinary toxicity also higher with EBRT. Vaginal brachytherapy use in both arms (per center practice) complicated interpretation.
Conclusions
Adjuvant pelvic EBRT provides no OS benefit in stage I-II endometrial cancer and adds significant bowel and urinary toxicity. Locoregional recurrence reduction with EBRT is modest and mostly at the vaginal cuff — addressable more safely with VBT alone.
Key Limitations
Key Limitations: VBT use in both arms (per center practice) was a major confounding factor — the control arm was not pure observation. Heterogeneous populations (stage I-II, multiple grades and histologies). ASTEC lymphadenectomy arm is separate — results of this combined analysis address EBRT only. No standardized staging. Predates molecular risk classification.
Clinical Context
The ASTEC/EN.5 combined analysis is the largest evidence base against adjuvant pelvic EBRT in stage I-II endometrial cancer. Combined with PORTEC-1 and GOG-99, it confirms no OS benefit from EBRT. Modern guidelines recommend VBT (not EBRT) for most intermediate-risk patients, with pelvic EBRT reserved for high-risk or stage III disease. The PORTEC-2 trial definitively established VBT non-inferiority to EBRT.
References
References: Blake P et al, Lancet 2009 (ASTEC/EN.5 combined)