# Short-course radiotherapy followed by chemotherapy before total mesorectal excision versus preoperative chemoradiotherapy in locally advanced rectal cancer (RAPIDO)

Source: https://onco.cc/key-papers/paper-bahadoer-rapido-short-course-radiotherapy-lancet-oncol-2021/  
OnCo record `paper-bahadoer-rapido-short-course-radiotherapy-lancet-oncol-2021` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Moving all the chemotherapy in front of the operation, after one week of radiotherapy, cut three-year treatment failure from 30.4 to 23.7 percent in high-risk rectal cancer.

## Summary

RAPIDO recruited from 54 centres in the Netherlands, Sweden, Spain, Slovenia, Denmark, Norway and the United States. Patients aged 18 or older with biopsy-proven, newly diagnosed, primary locally advanced rectal adenocarcinoma classified as high risk on pelvic MRI (cT4a or cT4b, extramural vascular invasion, cN2, involved mesorectal fascia, or enlarged lateral lymph nodes) were randomised 1:1. The experimental group received short-course radiotherapy (5 x 5 Gy over a maximum of eight days) followed by six cycles of CAPOX or nine of FOLFOX4 and then total mesorectal excision; the standard of care group received 28 daily fractions of 1.8 Gy to 50.4 Gy or 25 of 2.0 Gy to 50.0 Gy with concomitant capecitabine, then total mesorectal excision and, where hospital policy stipulated, adjuvant chemotherapy.

The primary endpoint was three-year disease-related treatment failure, defined as the first occurrence of locoregional failure, distant metastasis, new primary colorectal tumour or treatment-related death.

## Fields

- Kind: Key paper
- Last checked: 2026-09-24
- Tags: colorectal-evidence
- Journal: The Lancet Oncology
- Year: 2021
- DOI: 10.1016/S1470-2045(20)30555-6
- Authors: Bahadoer RR, Dijkstra EA, van Etten B, et al.
- Findings: 912 eligible patients (462 experimental, 450 standard of care); median follow-up 4.6 years.; Three-year disease-related treatment failure 23.7 percent (95 percent CI 19.8 to 27.6) against 30.4 percent (26.1 to 34.6): hazard ratio 0.75 (0.60 to 0.95, p=0.019).; Grade 3 or higher diarrhoea during preoperative therapy in 81 of 460 (18 percent) experimental patients against 41 of 441 (9 percent) standard-of-care patients.; Four treatment-related deaths in each group.
- What it means: The first total neoadjuvant therapy trial to change practice in high-risk rectal cancer, and the schedule that makes organ preservation possible by giving the tumour months rather than weeks to respond.
- Caveats: Longer follow-up showed more locoregional recurrence in the experimental arm, which the authors attributed in part to the surgery and pathology; the balance between distant and local control is still argued.; Adjuvant chemotherapy in the control arm depended on hospital policy, so the comparator was not uniform.; More grade 3 diarrhoea during preoperative treatment.

## Sources

- Lancet Oncol 2021: https://doi.org/10.1016/S1470-2045(20)30555-6
- PubMed: https://pubmed.ncbi.nlm.nih.gov/33301740/

## Connected records

- key papers: [Neoadjuvant chemotherapy with FOLFIRINOX and preoperative chemoradiotherapy for patients with locally advanced rectal cancer (UNICANCER-PRODIGE 23)](https://onco.cc/key-papers/paper-conroy-prodige-23-neoadjuvant-folfirinox-rectal-lancet-oncol-2021/), [Organ preservation in patients with rectal adenocarcinoma treated with total neoadjuvant therapy (OPRA)](https://onco.cc/key-papers/paper-garcia-aguilar-opra-organ-preservation-jco-2022/), [Rectal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up](https://onco.cc/key-papers/paper-esmo-rectal-cancer-guideline-ann-oncol-2017/)
- cancers: [Colorectal cancer](https://onco.cc/cancers/colorectal/), [Rectal cancer](https://onco.cc/cancers/rectal-cancer/)
- fronts: [Chemotherapy](https://onco.cc/fronts/chemotherapy/), [Radiation Therapy](https://onco.cc/fronts/radiation/), [Surgery & Interventional](https://onco.cc/fronts/surgery/)
- terms: [Chemoradiation (chemoradiotherapy, CRT)](https://onco.cc/terms/chemoradiation/), [Radiotherapy](https://onco.cc/terms/radiotherapy/), [Total mesorectal excision (TME)](https://onco.cc/terms/total-mesorectal-excision/), [Total neoadjuvant therapy (TNT, rectal cancer)](https://onco.cc/terms/total-neoadjuvant-therapy/)
- technologies: [IMRT / IGRT (modern external beam)](https://onco.cc/technologies/imrt-igrt/), [MRI](https://onco.cc/technologies/mri/)
- drugs: [Capecitabine](https://onco.cc/drugs/capecitabine/), [CAPOX (capecitabine, oxaliplatin)](https://onco.cc/drugs/capox/), [FOLFOX (5-FU, leucovorin, oxaliplatin)](https://onco.cc/drugs/folfox/), [Oxaliplatin](https://onco.cc/drugs/oxaliplatin/)
- trials: [RAPIDO](https://onco.cc/trials/rapido/)
- people: [Cornelis J. H. van de Velde](https://onco.cc/people/cornelis-van-de-velde/)
- bottlenecks: [Surgery and radiotherapy cure most, get least](https://onco.cc/bottlenecks/b-surgery-radiation-innovation/)
- journals: [The Lancet Oncology](https://onco.cc/journals/lancet-oncology/)
- roadmaps: [Colorectal cancer roadmap: from the adenoma-carcinoma sequence and the first screening trials to total mesorectal excision, oxaliplatin, RAS testing, immunotherapy for mismatch repair-deficient disease, ctDNA-guided treatment and organ preservation](https://onco.cc/roadmaps/colorectal-roadmap/)
- ideas: [Randomise organ preservation against surgery in mismatch repair-proficient rectal cancer, with bowel function as a co-primary endpoint](https://onco.cc/ideas/idea-crc-organ-preservation-randomised-in-pmmr-rectal/)

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