RAPIDO
Short-course radiotherapy followed by chemotherapy before total mesorectal excision (TME) versus preoperative chemoradiotherapy, TME, and optional adjuvant chemotherapy in locally advanced rectal cancer (RAPIDO): a randomised, open-label, phase 3 trial
Phase 3N = 920NCT01558921
- Population
- Biopsy-proven, newly diagnosed locally advanced rectal adenocarcinoma classified as high risk on pelvic MRI (cT4a/b, extramural vascular invasion, cN2, involved mesorectal fascia or enlarged lateral lymph nodes)
- Design
- Multicentre, open-label, randomised phase 3 trial in 54 centres in seven countries. Experimental group: short-course radiotherapy (5 x 5 Gy) followed by six cycles of CAPOX or nine cycles of FOLFOX4, then total mesorectal excision. Standard-of-care group: chemoradiotherapy (50.0 to 50.4 Gy with capecitabine), total mesorectal excision and, per hospital policy, adjuvant chemotherapy. 920 patients were randomly assigned between June 2011 and June 2016; 912 were eligible (462 and 450). Primary endpoint assessed in the intention-to-treat population.
- Primary endpoint
- Disease-related treatment failure
- Arms
- Standard of care (control, n = 450): Chemoradiotherapy (50.0 to 50.4 Gy with capecitabine), total mesorectal excision, optional adjuvant CAPOX or FOLFOX4
- Short-course radiotherapy then chemotherapy (experimental, n = 462): 5 x 5 Gy radiotherapy, then six cycles of CAPOX or nine cycles of FOLFOX4, then total mesorectal excision
- People
- Bahadoer RR, RAPIDO collaborative investigators
Disease-related treatment failureHR 0.75 (95% CI 0.60–0.95)Δ 36-month Disease-related treatment failure−6.7 pointsΔ Locoregional failure+4 pointsΔ Locoregional recurrence after R0/R1 resection+4 points
Show the numbers
| Endpoint | Analysis | Short-course radiotherapy then chemotherapy | Standard of care | Effect |
|---|---|---|---|---|
| Disease-related treatment failureIntention-to-treat population as stated by the authors; the analysis reported 912 eligible patients (462 and 450) of 920 randomisedFirst occurrence of locoregional failure, distant metastasis, new primary colorectal tumour or treatment-related death | primarymedian follow-up 4.6 yearsBahadoer 2021 | 23.7% at 3 y (19.8–27.6%) | 30.4% at 3 y (26.1–34.6%) | HR 0.75 (95% CI 0.60–0.95)P=0.019Cumulative probability at 3 years after randomisation, in the 912 eligible patients (462 experimental, 450 standard of care). |
| Locoregional failureEligible patients in the 5-year locoregional failure analysis (460 experimental, 446 standard of care)Locoregional failure, including early failure (no resection except for organ preservation, or R2 resection) and locoregional recurrence after R0/R1 resection | long term-updatemedian follow-up 5.6 yearsDijkstra 2023 | 12% | 8% | P=0.0754 of 460 versus 36 of 446 patients. |
| Locoregional recurrence after R0/R1 resectionPatients with an R0 or R1 resection in the 5-year analysis (431 experimental, 428 standard of care)Locoregional recurrence after an R0 or R1 resection | long term-updatemedian follow-up 5.6 yearsDijkstra 2023 | 10% | 6% | P=0.02744 of 431 versus 26 of 428 patients; a breached mesorectum was reported in 9 of 44 versus 1 of 26 recurrences (P=0.048). The abstract concludes that the reduction in disease-related treatment failure and distant metastases remained at 5 years. |
| Endpoint | Analysis | Short-course radiotherapy then chemotherapy | Standard of care | Effect |
|---|---|---|---|---|
| Disease-related treatment failureIntention-to-treat population as stated by the authors; the analysis reported 912 eligible patients (462 and 450) of 920 randomisedFirst occurrence of locoregional failure, distant metastasis, new primary colorectal tumour or treatment-related death | primarymedian follow-up 4.6 yearsBahadoer 2021 | 23.7% at 3 y (19.8–27.6%) | 30.4% at 3 y (26.1–34.6%) | HR 0.75 (95% CI 0.60–0.95)P=0.019Cumulative probability at 3 years after randomisation, in the 912 eligible patients (462 experimental, 450 standard of care). |
| Locoregional failureEligible patients in the 5-year locoregional failure analysis (460 experimental, 446 standard of care)Locoregional failure, including early failure (no resection except for organ preservation, or R2 resection) and locoregional recurrence after R0/R1 resection | long term-updatemedian follow-up 5.6 yearsDijkstra 2023 | 12% | 8% | P=0.0754 of 460 versus 36 of 446 patients. |
| Locoregional recurrence after R0/R1 resectionPatients with an R0 or R1 resection in the 5-year analysis (431 experimental, 428 standard of care)Locoregional recurrence after an R0 or R1 resection | long term-updatemedian follow-up 5.6 yearsDijkstra 2023 | 10% | 6% | P=0.02744 of 431 versus 26 of 428 patients; a breached mesorectum was reported in 9 of 44 versus 1 of 26 recurrences (P=0.048). The abstract concludes that the reduction in disease-related treatment failure and distant metastases remained at 5 years. |
Data table
| Endpoint | HR | 95% CI |
|---|---|---|
| Disease-related treatment failure | 0.75 | 0.6–0.95 |
Appears in
Sources
Bahadoer RR, Dijkstra EA, van Etten B, Marijnen CAM, Putter H, Kranenbarg EM, et al. Short-course radiotherapy followed by chemotherapy before total mesorectal excision (TME) versus preoperative chemoradiotherapy, TME, and optional adjuvant chemotherapy in locally advanced rectal cancer (RAPIDO): a randomised, open-label, phase 3 trial. Lancet Oncol. 2021;22(1):29-42.
Dijkstra EA, Nilsson PJ, Hospers GAP, Bahadoer RR, Meershoek-Klein Kranenbarg E, Roodvoets AGH, et al. Locoregional Failure During and After Short-course Radiotherapy Followed by Chemotherapy and Surgery Compared With Long-course Chemoradiotherapy and Surgery: A 5-Year Follow-up of the RAPIDO Trial. Ann Surg. 2023;278(4):e766-e772.