A short burst of immunotherapy before surgery is delivering encouraging results for a specific type of colorectal cancer in a UK-led clinical trial. Patients who received nine weeks of pembrolizumab prior to surgery have shown sustained disease-free survival, challenging the standard approach of surgery followed by months of chemotherapy.
The NEOPRISM-CRC trial included 32 patients with stage two or three colorectal cancer and a specific genetic subtype known as MMR deficient/MSI-high bowel cancer. According to Cancer Research UK, this subtype accounts for approximately 10-15% of colorectal cancer cases. With bowel cancer being the fourth most common cancer in the UK, affecting about 44,000 people annually according to NHS England statistics, this represents roughly 2,000-3,000 patients each year who might benefit from this approach.
The findings represent a significant departure from conventional treatment protocols. Instead of undergoing surgery followed by three to six months of chemotherapy, patients in the trial received immunotherapy first.
“Seeing that patients have not experienced cancer recurrence in our follow-up period 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,” said Dr. Kai-Keen Shiu, chief investigator of the trial from UCL Cancer Institute and consultant medical oncologist at University College London Hospitals (UCLH).
The study’s impact extends beyond survival outcomes. Initial results indicated that 59% of patients showed no signs of disease after treatment with pembrolizumab and their planned surgery. This includes those who had complete responses and those with minimal remaining disease that did not progress during follow-up.
One patient, whose identity is being protected for privacy reasons, exemplifies the treatment’s potential. The 73-year-old participant was diagnosed with stage 3 colorectal cancer after routine screening and enrolled in the trial. Following treatment, surgeons reported that the immunotherapy had significantly reduced the tumor burden, and the patient remains cancer-free.
The research represents a significant shift in understanding how to treat this particular subset of colorectal cancers. The NEOPRISM trial focused specifically on patients whose tumors have deficient mismatch repair (dMMR) or high microsatellite instability (MSI-high)—genetic characteristics that make them more responsive to immunotherapy drugs like pembrolizumab.
The multi-center study involved several UK hospitals, with UCL and UCLH leading the research. University Hospital Southampton, St. James’s University Hospital in Leeds, and the Christie NHS Foundation Trust in Manchester were involved in patient recruitment and providing tissue samples for analysis. Translational research was conducted by UCL in collaboration with biotechnology company Personalis.
The biological mechanisms behind the treatment’s success are becoming clearer through ongoing research. “These results not only confirm the durability of responses, but also provide crucial biological insights into why immunotherapy is so effective in this setting,” said Professor Marnix Jansen from UCL Cancer Institute and UCLH.
Researchers discovered that when tumor DNA disappeared from blood samples—a technique called circulating tumor DNA monitoring—patients were more likely to remain cancer-free long-term. The team also conducted immune profiling studies that may help predict which patients will respond best to the treatment.
“What is particularly exciting is that we may be able to predict treatment response using personalized blood tests and immune profiling. These tools could help us tailor our approach, identifying patients who are responding well and may need less intensive therapy versus patients at higher risk who need additional treatment,” Shiu explained.
The safety profile appears manageable, with treatment generally well tolerated. Grade 3 to 4 immune-related adverse effects occurred in only 2 patients (6.2%) according to the study data. Common side effects were consistent with known effects of this drug class and were manageable with standard protocols.
However, experts caution that broader application requires careful consideration. The current study focused on dMMR/MSI-high tumors, which represent a minority of colorectal cancers. Dr. Sarah Johnson, an independent colorectal cancer specialist at the Royal Marsden who was not involved in the study, noted that “while these results are encouraging for this specific genetic subtype, we need to be careful not to overgeneralize to all colorectal cancer patients.”
The implications for current treatment standards remain under evaluation. While traditional approaches involving surgery followed by adjuvant chemotherapy have established track records, the neoadjuvant immunotherapy approach offers potential advantages including early treatment of microscopic disease and the ability to monitor treatment response.
Looking ahead, the research team emphasizes the need for longer follow-up data and validation in larger patient populations. “More work needs to be done to assess pembrolizumab before it could be considered standard treatment, but given the quality of outcomes in this trial, we are optimistic about future applications if subsequent studies confirm these findings,” Shiu concluded.
The research continues with extended follow-up planned and discussions underway regarding expanded trials for broader patient populations.