# Randomise organ preservation against surgery in mismatch repair-proficient rectal cancer, with bowel function as a co-primary endpoint

Source: https://onco.cc/ideas/idea-crc-organ-preservation-randomised-in-pmmr-rectal/  
OnCo record `idea-crc-organ-preservation-randomised-in-pmmr-rectal` (Idea). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Half of rectal cancer patients given all their chemotherapy and radiotherapy first can keep their rectum. Nobody has ever randomised that against having the operation, so the trade-off between avoiding a stoma and the risk of the cancer regrowing is still guesswork.

## Summary

Habr-Gama watched 71 of 265 patients whose rectal cancers vanished after chemoradiotherapy and reported ten-year overall survival of 97.7 percent across the series; OPRA made the strategy plannable, with three-year survival free of total mesorectal excision of 53 percent after consolidation chemotherapy and disease-free survival matching the 75 percent historical rate. In mismatch repair-deficient disease the question has been answered emphatically: every one of 49 rectal cancers treated with six months of dostarlimab had a clinical complete response, 82 of 103 patients across both Cercek cohorts avoided surgery, and two-year recurrence-free survival was 92 percent.

For the mismatch repair-proficient 90 percent, the evidence remains single-arm or historically controlled. OPRA's comparison is against historical data; regrowth continues beyond three years; and the assumption that salvage surgery after regrowth costs nothing rests on subgroup comparisons within the same non-randomised cohort. Meanwhile the thing patients actually weigh, long-term bowel, urinary and sexual function after watch and wait against after total mesorectal excision, has never been a primary endpoint.

## Fields

- Kind: Idea
- Last checked: 2026-09-24
- Tags: colorectal-evidence
- Hypothesis: In mismatch repair-proficient locally advanced rectal cancer with a clinical complete response after total neoadjuvant therapy, watch and wait is non-inferior to immediate total mesorectal excision for five-year disease-free survival and superior for patient-reported bowel function at two years.
- Rationale: Organ preservation is already offered outside trials on the strength of OPRA and the international watch-and-wait registry, so the randomised comparison is becoming harder to run each year; and the function benefit that justifies the strategy has never been measured against the comparator it replaces.
- Proposed test: A randomised non-inferiority trial in patients with a clinical complete response after total neoadjuvant therapy, stratified by response assessment method, with five-year disease-free survival and two-year patient-reported bowel function as co-primary endpoints, MRI and endoscopic restaging centrally reviewed, and stoma-free survival, local regrowth and salvage resection rates reported as secondary outcomes. JANUS and the running total neoadjuvant therapy trials supply the platform.
- Maturity: being-tested-at-scale
- Actor: research

## Sources

- Garcia-Aguilar et al.: OPRA (J Clin Oncol 2022): https://europepmc.org/article/MED/35483010
- Cercek et al.: nonoperative management of mismatch repair-deficient tumours (N Engl J Med 2025): https://europepmc.org/article/MED/40293177
- ClinicalTrials.gov NCT05610163: https://clinicaltrials.gov/study/NCT05610163

## Connected records

- 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/), [Surgery roadmap: radical operations → less surgery → no surgery when a drug has done the work](https://onco.cc/roadmaps/surgery-roadmap/)
- cancers: [Colorectal cancer](https://onco.cc/cancers/colorectal/), [Rectal cancer](https://onco.cc/cancers/rectal-cancer/)
- fronts: [Radiation Therapy](https://onco.cc/fronts/radiation/), [Surgery & Interventional](https://onco.cc/fronts/surgery/)
- terms: [Clinical complete response (cCR)](https://onco.cc/terms/clinical-complete-response/), [Organ preservation (watch-and-wait, bladder-sparing, larynx preservation)](https://onco.cc/terms/organ-preservation/), [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/), [Robotic & minimally invasive surgery](https://onco.cc/technologies/robotic-surgery/)
- drugs: [Capecitabine](https://onco.cc/drugs/capecitabine/), [CAPOX (capecitabine, oxaliplatin)](https://onco.cc/drugs/capox/), [Dostarlimab](https://onco.cc/drugs/dostarlimab/), [FOLFOX (5-FU, leucovorin, oxaliplatin)](https://onco.cc/drugs/folfox/)
- trials: [AZUR-1](https://onco.cc/trials/azur-1/), [OPRA](https://onco.cc/trials/opra/), [PRODIGE 23](https://onco.cc/trials/prodige-23/), [RAPIDO](https://onco.cc/trials/rapido/)
- people: [Andrea Cercek](https://onco.cc/people/andrea-cercek/), [Angelita Habr-Gama](https://onco.cc/people/angelita-habr-gama/), [Julio Garcia-Aguilar](https://onco.cc/people/julio-garcia-aguilar/)
- bottlenecks: [Surgery and radiotherapy cure most, get least](https://onco.cc/bottlenecks/b-surgery-radiation-innovation/), [Toxicity and quality of life are undervalued](https://onco.cc/bottlenecks/b-toxicity-qol/), [Trial design, endpoints and cost](https://onco.cc/bottlenecks/b-trial-design/)
- key papers: [Nonoperative management of mismatch repair-deficient tumors](https://onco.cc/key-papers/paper-cercek-nonoperative-management-mismatch-repair-deficient-tumours-nejm-2025/), [Operative versus nonoperative treatment for stage 0 distal rectal cancer following chemoradiation therapy: long-term results](https://onco.cc/key-papers/paper-habr-gama-nonoperative-stage-0-rectal-ann-surg-2004/), [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/), [Short-course radiotherapy followed by chemotherapy before total mesorectal excision versus preoperative chemoradiotherapy in locally advanced rectal cancer (RAPIDO)](https://onco.cc/key-papers/paper-bahadoer-rapido-short-course-radiotherapy-lancet-oncol-2021/)

---
JSON: https://onco.cc/api/v1/entities/idea-crc-organ-preservation-randomised-in-pmmr-rectal.json