Dr Kai-Keen Shiu led a UK trial in which 32 people with stage II or III bowel cancer and the dMMR/MSI-high genetic profile took part in the NEOPRISM-CRC study. Shiu is a consultant medical oncologist at UCLH and the trial’s chief investigator from the UCL Cancer Institute.
The patients were recruited at five hospitals: UCL and UCLH, University Hospital Southampton, St. James's University Hospital in Leeds, and the Christie NHS Foundation Trust in Manchester.
Instead of receiving the usual chemotherapy after surgery, which lasts three to six months, participants were given pembrolizumab immunotherapy for up to nine weeks before their operations.
Researchers also developed personalised blood tests to identify patients most likely to benefit and to monitor tumor DNA. The disappearance of tumor DNA from the blood was strongly associated with finding no cancer left after treatment.
After pembrolizumab and surgery, 59% of participants had no detectable signs of disease. Those with small amounts of cancer remaining did not see it grow or spread during the follow-up period.
After 33 months, none of the 32 patients had experienced a recurrence. The absence of recurrences over nearly three years added confidence in pembrolizumab’s safety and effectiveness for high-risk bowel cancer patients.
The result was presented at the American Association for Cancer Research Annual Meeting in San Diego, California. It contrasts with the roughly 25% of patients treated with surgery followed by chemotherapy who are expected to relapse within three years.
The genetic profile, meaning DNA mismatch repair deficiency and high microsatellite instability, is found in around 10-15% of people with stage II or III bowel cancer. That amounts to roughly 2,000-3,000 cases each year in the UK.
Bowel cancer is the fourth most common cancer in the UK, where roughly 44,000 new cases are diagnosed each year. Around nine in ten people treated for stage one disease survive for at least five years, while five-year survival is 65% for stage III disease and 10% for stage IV disease.
Separate evidence has also tested immunotherapy alongside chemotherapy after surgery. The Phase 3 ATOMIC trial enrolled 712 patients with stage III dMMR colon cancer, randomly assigning them to twelve cycles of mFOLFOX6 chemotherapy or to the same treatment plus atezolizumab.
Adding atezolizumab reduced disease-free survival events by 50%, with a hazard ratio of 0.50 and a 95% confidence interval of 0.35 to 0.73. Three-year disease-free survival was 76.2% with chemotherapy alone and 86.3% with chemotherapy plus the checkpoint inhibitor, an absolute difference of 10.1%.
On 8 October 2026, the FDA cleared both intravenous Tecentriq and subcutaneous Tecentriq Hybreza with mFOLFOX6 for resected stage III dMMR tumors. The NEOPRISM-CRC researchers said individualised blood tests and immune profiling could help distinguish patients who may need lower-intensity treatment from those who need additional treatment.
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