RAPIDO: short-course radiotherapy followed by chemotherapy before surgery for high-risk locally advanced rectal cancer
Giving all treatment before surgery, with a week of radiotherapy followed by four to five months of chemotherapy, halved distant metastases and doubled the complete response rate compared with standard chemoradiation in high-risk rectal cancer.
Overview
Phase 3 trial of 912 patients with high-risk locally advanced rectal adenocarcinoma randomised to short-course radiotherapy (5 x 5 Gy) followed by six cycles of CAPOX or nine of FOLFOX then total mesorectal excision, or standard long-course chemoradiotherapy, surgery and optional adjuvant chemotherapy.
Disease-related treatment failure at three years was 23.7 versus 30.4 percent, distant metastases 20.0 versus 26.8 percent and pathological complete response 28 versus 14 percent; longer follow-up showed more locoregional failures in the experimental arm.
- Three-year disease-related treatment failure 23.7 percent vs 30.4 percent; hazard ratio 0.75.
- Pathological complete response 28 percent vs 14 percent.
Total neoadjuvant therapy is now a standard for high-risk rectal cancer, improving compliance with chemotherapy and enabling organ preservation, though the locoregional recurrence signal favours long-course chemoradiation in some patients.
- Five-year locoregional failure was higher with the experimental arm (10 vs 6 percent).
- No overall survival difference.