Neoadjuvant Pembrolizumab Eliminates Recurrence in High-Risk Bowel Cancer

The NEOPRISM-CRC trial, run by UCL and UCLH, enrolled 32 patients with stage II/III MMR-deficient/MSI-high bowel cancer. Each received nine weeks of pembrolizumab before surgery. After a median 33-month follow-up, none have shown disease recurrence.

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UK bowel cancer causes about 44,000 new cases each year, ranking fourth among cancers. Standard treatment combines surgery with 3-6 months of chemotherapy, yielding a 25 % three-year relapse rate. The MMR-deficient/MSI-high subtype represents 10-15 % of UK cases (?2,000-3,000 annually). Patients were recruited from UCLH, University Hospital Southampton, St James’s University Hospital (Leeds), and The Christie NHS Foundation Trust (Manchester). Translational work involved UCL and Personalis. Investigators: Dr Kai-Keen Shiu, Prof Marnix Jansen, Yanrong Jiang (UCL Cancer Institute).

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At surgery, 59 % of patients had no detectable tumor. Recurrence after 33 months was 0 % versus an expected 25 % under standard care. Serial ctDNA testing showed that clearance after pembrolizumab strongly predicted disease-free status. Immune-profiling of pretreatment tissue identified response-associated signatures, suggesting a path toward personalized therapy.

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Christopher Burston, 73, was diagnosed with stage III disease in February 2023. He received three pembrolizumab doses before surgery, reported minimal side effects, and described the tumor as “melted away.” Three years later he remains cancer-free and feels “back to normal.”

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Dr Shiu said the lack of recurrence after nearly three years confirms pembrolizumab’s safety and efficacy and points to blood-based assays for response prediction. Prof Jansen noted durable responses and new mechanistic insight. Jiang reported that ctDNA clearance matched long-term remission and that immune profiling may soon guide treatment choices.

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The cohort’s size (32 patients) and 33-month follow-up limit generalizability. Larger, randomized studies are planned to validate biomarkers and to test whether neoadjuvant pembrolizumab can replace adjuvant chemotherapy for this high-risk subgroup.

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• “Seeing that no patients have experienced a cancer recurrence after almost three years of follow-up is extremely encouraging and strengthens our confidence that pembrolizumab is a safe and highly effective treatment to improve outcomes in patients with high-risk bowel cancers.” — Dr Kai-Keen Shiu, UCL Cancer Institute

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• “What is particularly exciting is that we now may be able to predict who will respond to the treatment using personalized blood tests and immune profiling.” — Dr Kai-Keen Shiu, UCL Cancer Institute

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• “These results not only confirm the durability of responses we saw almost three years ago, but also provide crucial biological insights into why immunotherapy is so effective in this setting.” — Professor Marnix Jansen, UCL Cancer Institute

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• “The outcome of the surgery was essentially that the cancer had melted away… The immunotherapy had an almost immediate effect.” — Christopher Burston, patient

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