A newer report of this study has been published: Nonoperative Management of Mismatch Repair-Deficient Tumors (2025)
About 5 to 10 percent of rectal cancers have a genetic feature called "mismatch repair deficiency" (dMMR or MSI-H). In this small study, instead of chemotherapy, radiotherapy and surgery, patients first received only 6 months of the immunotherapy drug dostarlimab, given into a vein every 3 weeks. In all of the first 12 patients, the tumour disappeared completely on examination and scans, and none of them needed surgery or radiotherapy; no serious side effects were seen. This means keeping the rectum and avoiding problems such as a stoma bag, infertility and sexual problems. However, the number of patients was small, and this treatment should be given only in specialist centres with close follow-up. Testing the tumour sample for MMR/MSI is recommended for everyone with rectal cancer.
Locally advanced (stage II or III) dMMR/MSI-H rectal cancer
| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Dostarlimab | 500 mg | IV | Day 1 |
Regimen of the Memorial Sloan Kettering phase 2 trial. If tumour remained, the protocol called for standard chemoradiotherapy (5040 cGy in 28 fractions with capecitabine) followed by TME. ESMO 2025 suggests this treatment at level [II, A], but this use does not yet have FDA or EMA approval.
dMMR/MSI-H stage II or III rectal adenocarcinoma (and stage I to III dMMR solid tumours); investigational — this use is not in the dostarlimab FDA label
| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Dostarlimab | 500 mg | IV infusion over 30 minutes | Every 3 weeks |
As in the registered trial protocol. Only in experienced centres with regular surveillance (digital rectal examination, endoscopy, pelvic MRI).
On the page “Immunotherapy and organ preservation in dMMR tumours” · Regimens from the key studies
Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.
Dostarlimab 500 mg IV over 30 minutes once every 3 weeks for 6 months (9 cycles of 21 days).
If there is a clinical complete response after completion of dostarlimab, the patient is followed without chemoradiotherapy or surgery (nonoperative management). If tumour remains, standard chemoradiotherapy (capecitabine 825 mg/m² twice daily concurrently with radiotherapy) followed by surgery is given per protocol.
Source of the regimen details: ClinicalTrials.gov NCT04165772 (dostarlimab 500 mg IV over 30 minutes every 3 weeks; capecitabine 825 mg/m² twice daily with radiotherapy) and the full text of the follow-up paper of the same trial (Cercek 2025, PMC12661660: 500 mg every 3 weeks for 9 cycles)
Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.
Patients with previously untreated stage 2 or 3 (locally advanced) mismatch repair-deficient (dMMR) rectal adenocarcinoma.
Primary endpoints: sustained clinical complete response 12 months after completion of dostarlimab or pathological complete response after dostarlimab (with or without chemoradiotherapy); and overall response to neoadjuvant dostarlimab with or without chemoradiotherapy.
No grade 3 or higher adverse events were reported in the initial report.
This initial report introduced the concept of "organ preservation with immunotherapy alone" in dMMR rectal cancer and formed the basis for the expanded study (Cercek 2025, NEJM). In December 2024 the FDA granted dostarlimab Breakthrough Therapy designation for these patients, and in August 2026 it accepted the application for approval of this use with priority review (target action date: February 2027). Thus, as of October 2026, dostarlimab does not yet have formal FDA approval for locally advanced dMMR rectal cancer, and its use in this setting should be in experienced centres or within a clinical trial.
A single-arm, single-centre study with very few patients (12) and short follow-up (6 to 25 months); the long-term durability of response was not known in this report. Nonoperative management requires intensive follow-up with MRI, endoscopy and examination. The results apply only to dMMR/MSI-H tumours and cannot be generalised to mismatch repair-proficient (pMMR) rectal cancers, which make up the majority of cases.
This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.
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