This study continues and expands the well-known dostarlimab trial in rectal cancer, and this time it also included people with other dMMR cancers (such as colon, stomach, oesophagus, bladder and bile duct cancers). Patients received dostarlimab into a vein for 6 months. All 49 patients with rectal cancer who finished treatment had a complete response and were followed without surgery. In the other cancers, about two-thirds of patients had a complete response. Overall, 82 of 103 people did not need surgery, and 92% of patients were free of recurrence after 2 years. Side effects were mild in most patients. Importantly, patients who did not have a complete response did not lose the chance of surgery. This treatment is not yet formally approved, and the decision should be made with a specialist team.
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 once every 3 weeks for 9 cycles (6 months).
Patients with a clinical complete response could choose nonoperative management (active surveillance without surgery); patients with residual tumour received standard treatment per protocol (in rectal cancer: chemoradiotherapy) followed by surgery.
Source of the regimen details: Full text of the paper in PMC (PMC12661660): "dostarlimab 500 mg IV every 3 weeks for 9 cycles"; ClinicalTrials.gov NCT04165772
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 stage 1, 2 or 3 mismatch repair-deficient (dMMR; loss of MLH1, MSH2, MSH6 or PMS2 expression on immunohistochemistry) solid tumours that were resectable with curative intent. Cohort 1: locally advanced rectal cancer. Cohort 2: non-rectal tumours, including colon, gastric, oesophageal and gastro-oesophageal junction, urothelial (bladder and urinary tract), prostate, periampullary and cholangiocarcinoma. The median age of all patients was 57 years.
Primary endpoint (in cohort 1): sustained clinical complete response at 12 months.
Other endpoints: recurrence-free survival and safety.
Most patients (95%) had either reversible grade 1 or 2 adverse events (60%) or no adverse events (35%). The most common grade 1 or 2 events were fatigue (23%), pruritus (20%) and rash/dermatitis (20%). Four patients had grade 3 events (diabetes, lung infection, encephalitis and neutropenia, 1% each) and one patient had grade 4 neutropenia. No patient lost the opportunity for curative surgery during or after treatment.
This study showed that organ preservation with neoadjuvant immunotherapy may be feasible beyond rectal cancer, in other dMMR solid tumours. In December 2024 the FDA granted dostarlimab Breakthrough Therapy designation for locally advanced dMMR/MSI-H rectal cancer, and in August 2026 it accepted the application for approval of this use for priority review (target date: February 2027). As of October 2026, neoadjuvant dostarlimab in rectal cancer or other dMMR tumours is unapproved and investigational, and in non-rectal tumours the evidence is still limited to this single-arm study.
A single-arm, single-centre trial without a comparison group. Median follow-up for recurrence (20 months) is still short. Cohort 2 was a heterogeneous mix of tumour types with few patients of each type (for example 15 gastric, 3 oesophageal and 3 gastro-oesophageal junction); the tumours that most often did not reach a clinical complete response were prostate and gastro-oesophageal cancers. The definition and monitoring of clinical complete response differ between organs and require intensive follow-up.
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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