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RAPIDO
In high-risk locally advanced rectal cancer, does short-course radiotherapy followed by chemotherapy reduce treatment failure compared with standard long-course chemoradiotherapy?
Population
920 patients with high-risk locally advanced rectal cancer
3-year disease-related treatment failure
23.7% vs 30.4%
Absolute reduction 6.7 points; NNT 15
Pathologic complete response
≈28% vs 14%
Large increase with the experimental strategy
Grade ≥3 diarrhoea
18% vs 9%
Absolute increase 9 points; NNH 12
Absolute Effect
NNT: 15, based on 3-year disease-related treatment failure. The early disease-control advantage was clinically meaningful.
NNH: 12, based on grade ≥3 diarrhoea. Gastrointestinal toxicity increased with the intensified pathway.
Critical interpretation
RAPIDO is an important total-neoadjuvant-treatment trial, but the early reduction in treatment failure should not be equated automatically with an overall survival advantage. Longer follow-up identified a local-regional recurrence trade-off, illustrating why absolute effects must be revisited at mature time horizons.
Current-practice context · reviewed 14 October 2026
RAPIDO established a total-neoadjuvant strategy with short-course RT followed by chemotherapy as an effective way to reduce early disease-related treatment failure in MRI-defined high-risk rectal cancer, but longer follow-up showed increased locoregional recurrence. TNT is now an important standard for high-risk locally advanced rectal cancer, yet the exact sequence should be selected using MRI risk, response goals, sphincter/organ-preservation plans and current guideline evidence.
Current guideline guidance ↗