Background
Phase III RCT (EORTC 22861). 110 patients with locally advanced anal canal carcinoma (T3–T4 or any N+). Randomized to RT alone vs CRT (5-FU + mitomycin C + RT). RT: 45 Gy in 5 weeks + 15 Gy boost (external beam or brachytherapy) after 6-week gap. CRT: same RT + 5-FU 750 mg/m²/d continuous infusion days 1–5 and 36–40 + mitomycin C 15 mg/m² day 1. Key trial establishing CRT benefit in locally advanced (T3–T4/N+) anal cancer.
Interventions and follow up
Arm A: RT alone (45 Gy + 15 Gy boost)
Arm B: CRT — same RT + 5-FU (days 1–5 and 36–40) + mitomycin C (day 1)
Primary endpoint: Complete response, locoregional control
mFollow up: Median 52 month
Arm B: CRT — same RT + 5-FU (days 1–5 and 36–40) + mitomycin C (day 1)
Primary endpoint: Complete response, locoregional control
mFollow up: Median 52 month
Results
Complete response: 54% (RT alone) vs 80% (CRT), P=.02
5-year locoregional control: 50% (RT alone) vs 68% (CRT), P=.02
5-year colostomy-free survival: 40% (RT alone) vs 72% (CRT), P=.002
5-year OS: 52% (RT alone) vs 65% (CRT), P=.17 — not significant
5-year locoregional control: 50% (RT alone) vs 68% (CRT), P=.02
5-year colostomy-free survival: 40% (RT alone) vs 72% (CRT), P=.002
5-year OS: 52% (RT alone) vs 65% (CRT), P=.17 — not significant
Adverse events
Main adverse events: Acute grade 3–4 toxicity higher in CRT arm (late toxicity similar). No treatment-related deaths.
Conclusions
CRT with 5-FU and mitomycin C significantly improved complete response, locoregional control, and colostomy-free survival compared with RT alone in locally advanced anal cancer, with a trend toward improved OS.
Key Limitations
Key Limitations: Small sample size (110 patients) limits statistical power for OS analysis. Predominantly T3–T4 and node-positive patients — less applicable to early-stage disease. A 6-week gap was mandated between initial RT and boost, which is no longer standard practice. Predates PET staging and IMRT.
Clinical Context
Together with the UKCCR trial, the EORTC 22861 trial provided the evidence base for concurrent CRT as definitive treatment for anal cancer. The results are most relevant for locally advanced (T3–T4/N+) tumors. Modern guidelines (NCCN, ESMO) recommend definitive 5-FU + MMC + IMRT at 50.4–54 Gy for T2–T4 anal cancer.
References