Background
Phase III RCT (GOG-99). 392 patients with stage IB, IC, IIA, IIB (old FIGO 1988) or occult stage IIIA endometrial carcinoma after comprehensive surgical staging (TAH-BSO + pelvic and paraaortic lymph node dissection ± omentectomy). Randomized to adjuvant pelvic EBRT (50.4 Gy) vs observation. Unlike PORTEC-1, full surgical staging was required, allowing comparison of EBRT benefit in a staged population. Identified the "high-intermediate risk" (HIR) subgroup: ≥2 risk factors (age ≥70, grade 2–3, LVSI, outer 1/3 myometrial invasion) or grade 3 with LVSI and any invasion.
Interventions and follow up
Arm A: Pelvic EBRT 50.4 Gy (adjuvant, after comprehensive surgical staging)
Arm B: Observatio
Primary endpoint: Cumulative recurrence rate, OS
mFollow up: 4 year
Arm B: Observatio
Primary endpoint: Cumulative recurrence rate, OS
mFollow up: 4 year
Results
4-year cumulative recurrence: 3% (EBRT) vs 12% (observation), P<.001
4-year OS: 92% (EBRT) vs 86% (observation), P=.09 — not significant
HIR subgroup 4-year cumulative recurrence: 13% (EBRT) vs 27% (observation) — greatest absolute benefit
Low-intermediate risk recurrence: 1% vs 6% — small absolute benefit
4-year OS: 92% (EBRT) vs 86% (observation), P=.09 — not significant
HIR subgroup 4-year cumulative recurrence: 13% (EBRT) vs 27% (observation) — greatest absolute benefit
Low-intermediate risk recurrence: 1% vs 6% — small absolute benefit
Adverse events
Main adverse events: EBRT was associated with significantly more GI, urinary, and hematologic toxicity vs observation. Grade 3–4 hematologic toxicity: 4.3% (EBRT) vs 0.4%. Grade 3–4 GI toxicity: 3.5% vs 0%.
Conclusions
Pelvic EBRT significantly reduced recurrence after comprehensive surgical staging in stage I-II endometrial cancer but did not improve OS. The HIR subgroup had the greatest absolute recurrence reduction. For low-intermediate risk patients, the absolute benefit of EBRT is small and must be weighed against toxicity.
Key Limitations
Key Limitations: Comprehensive surgical staging was required — selection bias toward surgically staged patients in good performance status. Full lymph node dissection may itself reduce recurrence (therapeutic staging), diluting the apparent RT benefit. The HIR definition has been refined multiple times since this trial. 4-year follow-up is relatively short for endometrial cancer. Vaginal brachytherapy was not systematically used or compared.
Clinical Context
GOG-99 identified the HIR subgroup concept, which became foundational for modern risk stratification in endometrial cancer. Current NCCN guidelines define high-intermediate risk using GOG-99 criteria (modified). VBT (PORTEC-2) is preferred over EBRT for HIR patients after comprehensive staging. High-risk (stage III, high-grade) patients benefit from combined chemo + RT (PORTEC-3, GOG 258).
References
References: Keys HM et al, Gynecol Oncol 2004 (GOG-99)