Background
Phase III RCT (Trans-Tasman Radiation Oncology Group). 326 patients with cT3N0-2 rectal cancer, ≤12 cm from anal verge. Randomized 1:1 to short-course preoperative RT (SCRT: 25 Gy/5 fx, surgery in 1 week) versus long-course CRT (LCCRT: 50.4 Gy/28 fx + 5-FU continuous infusion, surgery in 4–6 weeks). Primary endpoint: local recurrence at 3 years.
Interventions and follow up
Arm A: SCRT: 25 Gy in 5 fractions → TME within 7 day
Arm B: LCCRT: 50.4 Gy in 28 fractions + 5-FU 225 mg/m²/day CI → TME at 4–6 week
Primary endpoint: Local recurrence rate at 3 year
mFollow up: 5.9 year
Arm B: LCCRT: 50.4 Gy in 28 fractions + 5-FU 225 mg/m²/day CI → TME at 4–6 week
Primary endpoint: Local recurrence rate at 3 year
mFollow up: 5.9 year
Results
3-yr local recurrence: 7.5% (SCRT) vs 4.4% (LCCRT), P=.24 — non-inferior
5-yr OS: 74% vs 70%, P=.62 — no difference
pCR: 0.7% (SCRT) vs 15% (LCCRT), P<.001
Sphincter preservation: No significant difference
5-yr OS: 74% vs 70%, P=.62 — no difference
pCR: 0.7% (SCRT) vs 15% (LCCRT), P<.001
Sphincter preservation: No significant difference
Adverse events
Main adverse events: Grade ≥3 acute toxicity: 29% (LCCRT) vs 9% (SCRT), P<.001. LCCRT higher acute toxicity but similar late toxicity.
Conclusions
Short-course RT was non-inferior to long-course CRT for local recurrence (7.5% vs 4.4%) and OS at 3 years. LCCRT achieves substantially higher pCR rates (15% vs 0.7%), making it preferred when downstaging or organ preservation is the goal. Both approaches are valid; patient-specific goals determine choice.
Key Limitations
Key Limitations: Non-inferiority margin was pre-specified at 10% — within the bound but with wide confidence intervals. SCRT followed by immediate surgery cannot achieve downstaging or sphincter preservation at the same rate as LCCRT. The pCR disparity (15% vs 0.7%) limits applicability of SCRT when organ preservation or watch-and-wait is desired. This trial was not designed for SCRT followed by delayed surgery (interval RT strategy now being studied in RAPIDO-like designs).
Clinical Context
Ngan confirmed that SCRT and LCCRT are equivalent for local control in patients with T3N0-2 disease not requiring downstaging. SCRT is preferred for convenience and lower acute toxicity when downstaging is not needed. LCCRT remains standard when downstaging, sphincter preservation, or organ preservation (watch-and-wait) is the goal. Stockholm III further compared SCRT with delayed surgery, which achieves downstaging comparable to LCCRT.
References
References: Ngan SY et al, J Clin Oncol 2012