# Nonoperative management of mismatch repair-deficient tumors

Source: https://onco.cc/key-papers/paper-cercek-nonoperative-management-mismatch-repair-deficient-tumours-nejm-2025/  
OnCo record `paper-cercek-nonoperative-management-mismatch-repair-deficient-tumours-nejm-2025` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

The extension of the rectal dostarlimab result to every organ: 49 of 49 rectal cancers and 35 of 54 other early-stage mismatch repair-deficient cancers disappeared on six months of one drug, and 82 patients avoided surgery altogether.

## Summary

Cercek, Foote, Rousseau and colleagues conducted a phase 2 study in which patients with stage I, II or III mismatch repair-deficient solid tumours amenable to curative-intent surgery were treated with neoadjuvant dostarlimab, a PD-1 blocking agent, for six months. Response was assessed in two cohorts: cohort 1 had mismatch repair-deficient locally advanced rectal cancer and cohort 2 had mismatch repair-deficient non-rectal solid tumours. Patients with a clinical complete response could elect non-operative management; those with residual disease were to undergo resection. The primary end point, assessed in cohort 1, was a sustained clinical complete response at 12 months.

The option of curative resection was not compromised during or after treatment in any patient, which is the safety claim that makes the strategy defensible outside a trial.

## Fields

- Kind: Key paper
- Last checked: 2026-09-24
- Tags: colorectal-evidence
- Journal: New England Journal of Medicine
- Year: 2025
- DOI: 10.1056/NEJMoa2404512
- Authors: Cercek A, Foote MB, Rousseau B, et al.
- Findings: All 49 patients in cohort 1 who completed treatment had a clinical complete response and elected non-operative management; 37 had a sustained clinical complete response at 12 months, meeting the efficacy criterion.; In cohort 2, 35 of 54 patients who completed treatment had a clinical complete response and 33 elected non-operative management.; Across both cohorts, 84 of 103 patients who completed treatment had a clinical complete response and 82 did not undergo surgery.; Recurrence-free survival at two years 92 percent (95 percent CI 86 to 99) among all 117 patients, at a median 20.0 months of follow-up for recurrence.; 95 percent of patients had reversible grade 1 or 2 adverse events (60 percent) or none (35 percent).
- What it means: For mismatch repair-deficient rectal cancer, six months of a single antibody now replaces chemotherapy, radiotherapy and an operation, and the same appears to be true for early-stage mismatch repair-deficient cancers of other organs.
- Caveats: Single-arm phase 2 with no randomised comparison against chemoradiotherapy and surgery; AZUR-1 is the registrational multicentre version.; Median follow-up for recurrence is 20 months, short for an organ-preservation strategy.; Applies only to the mismatch repair-deficient minority, and depends on high-quality restaging by endoscopy and MRI that not every centre can provide.

## Sources

- N Engl J Med 2025: https://doi.org/10.1056/NEJMoa2404512
- PubMed: https://pubmed.ncbi.nlm.nih.gov/40293177/
- Europe PMC full text (PMC12661660): https://europepmc.org/article/MED/40293177

## Connected records

- key papers: [Dostarlimab alone cures mismatch-repair-deficient rectal cancer without surgery or radiotherapy](https://onco.cc/key-papers/paper-cercek-dmmr-rectal-nejm-2022/), [NICHE-2: a single dose of ipilimumab and two of nivolumab before surgery clears dMMR colon cancer in most patients](https://onco.cc/key-papers/paper-niche-2-neoadjuvant-colon-nejm-2024/), [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/)
- cancers: [Colorectal cancer](https://onco.cc/cancers/colorectal/), [Mismatch-repair deficient (MSI-high) colorectal cancer](https://onco.cc/cancers/msi-high-colorectal/), [Rectal cancer](https://onco.cc/cancers/rectal-cancer/)
- fronts: [Immunotherapy](https://onco.cc/fronts/immunotherapy/), [Surgery & Interventional](https://onco.cc/fronts/surgery/)
- technologies: [Immune checkpoint inhibitors](https://onco.cc/technologies/checkpoint-inhibitor/)
- targets: [Mismatch repair proteins (MLH1, MSH2, MSH6, PMS2)](https://onco.cc/targets/mmr/), [PD-1](https://onco.cc/targets/pd1/)
- drugs: [Dostarlimab](https://onco.cc/drugs/dostarlimab/)
- companies: [GSK](https://onco.cc/companies/gsk/)
- institutions: [Memorial Sloan Kettering Cancer Center](https://onco.cc/institutions/mskcc/)
- terms: [Clinical complete response (cCR)](https://onco.cc/terms/clinical-complete-response/), [Complete response](https://onco.cc/terms/complete-response/), [Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR)](https://onco.cc/terms/msi/), [Organ preservation (watch-and-wait, bladder-sparing, larynx preservation)](https://onco.cc/terms/organ-preservation/)
- trials: [AZUR-1](https://onco.cc/trials/azur-1/)
- people: [Andrea Cercek](https://onco.cc/people/andrea-cercek/)
- 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/)
- journals: [New England Journal of Medicine](https://onco.cc/journals/nejm/)
- 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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