Background
Phase III RCT (n=515) of newly diagnosed, treatment-naïve cT4 or fixed cT3 rectal cancer, comparing short-course radiotherapy with consolidation chemotherapy vs long-course chemoradiotherapy.
Interventions and follow up
Arm A: RT 5×5 Gy (25 Gy) over 5 days, then 3 courses FOLFOX4, then surgery 10–11 weeks from start of RT
Arm B: chemoradiotherapy 28×1.8 Gy (50.4 Gy) over 5.5 weeks with bolus 5-FU 325 mg/m2/day + leucovorin 20 mg/m2/day D1–5 and 29–33, plus oxaliplatin 50 mg/m2 weekly ×5; surgery 10–11 weeks from start of RT
Primary endpoint: R0 resection rate
Median follow up: 35 months (R0); 7 years (survival update)
Arm B: chemoradiotherapy 28×1.8 Gy (50.4 Gy) over 5.5 weeks with bolus 5-FU 325 mg/m2/day + leucovorin 20 mg/m2/day D1–5 and 29–33, plus oxaliplatin 50 mg/m2 weekly ×5; surgery 10–11 weeks from start of RT
Primary endpoint: R0 resection rate
Median follow up: 35 months (R0); 7 years (survival update)
Results
R0 resection rate: 77% vs 71%, arm A vs B; P=.07
pCR: 16% vs 12%; P=.17
3-yr OS: 73% vs 65%; P=.046
3-yr DFS: 53% vs 52%; P=.85
8-yr OS: 49% vs 49%; HR 0.90, 95% CI 0.70–1.15; P=.38
8-yr DFS: 43% vs 41%; HR 0.95, 95% CI 0.75–1.19; P=.65
pCR: 16% vs 12%; P=.17
3-yr OS: 73% vs 65%; P=.046
3-yr DFS: 53% vs 52%; P=.85
8-yr OS: 49% vs 49%; HR 0.90, 95% CI 0.70–1.15; P=.38
8-yr DFS: 43% vs 41%; HR 0.95, 95% CI 0.75–1.19; P=.65
Adverse events
Acute grade 3–4: 11% vs 9%, arm A vs B (lower with short-course)
Late toxicity: similar between arms; no excess surgical morbidity
Late toxicity: similar between arms; no excess surgical morbidity
Conclusions
There was no difference in local efficacy between short-course RT with consolidation chemotherapy and long-course chemoradiotherapy in cT4 or fixed cT3 rectal cancer. The early 3-year OS advantage for short-course was not maintained at 8 years.
Key Limitations
R0 resection (primary endpoint) was not significantly different. The 3-year OS difference was likely a chance finding, as it disappeared on the 8-year update. Open-label design and heterogeneous advanced/fixed tumors.
Clinical Context
Supports short-course RT with consolidation chemotherapy as an equivalent option to long-course chemoradiotherapy for advanced/fixed rectal cancer, informing total neoadjuvant therapy strategies under ASCO/ESMO guidance. Long-term update: Cisel B et al, Ann Oncol, 2019, PMID: 31192355.