Dostarlimab alone cures mismatch-repair-deficient rectal cancer without surgery or radiotherapy
Six months of the PD-1 antibody dostarlimab made every tumour disappear in a small group of patients with mismatch-repair-deficient rectal cancer, allowing them to avoid chemotherapy, radiotherapy and surgery.
Single-arm phase 2 trial of patients with stage II-III mismatch-repair-deficient locally advanced rectal adenocarcinoma treated with dostarlimab 500 mg every three weeks for six months, with the plan to proceed to chemoradiotherapy and surgery only if disease persisted.
All 12 patients who completed treatment at the time of the report had a clinical complete response on endoscopy, MRI and PET, and none had needed chemoradiotherapy or surgery at a follow-up of 6-25 months. Later expansions confirmed sustained complete responses in over 40 patients. It showed that a subset of solid tumours can be cured by immunotherapy alone with total organ preservation, and led to guideline endorsement and a breakthrough designation.
- Clinical complete response in 12 of 12 patients (100%) who completed six months of dostarlimab.
- No patient required chemoradiotherapy or surgery, and no progression or recurrence during follow-up (6-25 months at publication).
- No grade 3 or higher adverse events.
- Subsequent expansion (2024-2025) reported sustained complete responses in over 40 rectal patients, with the approach extended to other dMMR tumour types.
Patients with rectal cancer whose tumour is mismatch-repair deficient (about 5-10% of rectal cancers) can now be offered immunotherapy alone with the realistic expectation of avoiding surgery, radiotherapy and a permanent stoma. This requires mismatch repair testing on the diagnostic biopsy, close endoscopic and MRI surveillance, and treatment in an experienced centre. It does not apply to the 90% of rectal cancers that are mismatch-repair proficient.
- Very small single-centre study with short follow-up at publication; durability beyond a few years is still being established.
- Clinical complete response is not the same as pathological complete response; surveillance must be rigorous and long-term.
- Most patients were treated at one specialist centre; reproducibility in routine practice is uncertain.
- Six months of dostarlimab is expensive and access is uneven.
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