Patients with a particular form of bowel cancer remained recurrence-free for almost three years after receiving a short course of immunotherapy before surgery, according to new results from the NEOPRISM-CRC clinical trial led by researchers at UCL and UCLH.
The results, scheduled to be presented at the American Association for Cancer Research (AACR) 2026 Annual Meeting in April, extend previous findings from the trial. These initial results showed that nine weeks of treatment with the immunotherapy drug pembrolizumab before surgery caused significant tumor shrinkage in people with stage two or three bowel cancer.
Previous data showed that 59% of patients had no detectable signs of disease after treatment with pembrolizumab and their planned surgery for bowel cancer.
Zero recurrence after 33 months
After 33 months of follow-up, none of the patients treated in the trial had experienced a recurrence of their cancer. This was true for both patients who had no signs of cancer after treatment and those who still had small amounts of disease. In the latter group, the remaining cancer did not grow or spread during follow-up.
For comparison, about 25% of patients treated with the standard surgical approach followed by chemotherapy are expected to relapse within three years. The results suggest that administering a short course of immunotherapy before surgery could provide more durable cancer control for this specific type of bowel cancer than the usual combination of surgery and postoperative chemotherapy.
Researchers also studied blood samples to determine why the treatment worked so well and find ways to identify patients most likely to benefit. They developed personalized blood tests intended to quickly show whether the treatment had worked and whether traces of cancer were still circulating in the blood.
Dr Kai-Keen Shiu, chief investigator of the trial at the UCL Cancer Institute and consultant medical oncologist at UCLH, said: “Finding that no patients experienced a cancer recurrence after almost three years of follow-up is extremely encouraging and reinforces our confidence that pembrolizumab is a safe and highly effective treatment for improving outcomes in patients with high-risk bowel cancers.
“What is particularly exciting is that we may now be able to predict who will respond to treatment using personalized blood tests and an immune profile. These tools could help us tailor our approach, identifying patients who are doing well and who may need less treatment before and after surgery compared to patients at higher risk of disease progression or relapse and who need additional treatment.
Bowel cancer survival varies by stage
Bowel cancer is the fourth most common cancer in the UK, with around 44,000 new cases diagnosed each year. It continues to most commonly affect older people, although rates among people younger than 50 have increased in recent decades.
As with many cancers, outcomes are much better when bowel cancer is detected early. Around nine in ten people treated for stage one bowel cancer survive at least five years. However, some tumor subtypes respond less effectively to treatment and are more likely to come back. Five-year survival drops to 65% for stage three bowel cancer and 10% for stage four cancer.
The NEOPRISM-CRC trial recruited 32 patients with stage two or three bowel cancer and a particular genetic profile (MMR-deficient/MSI-high bowel cancer) from five hospitals across the UK. Around 10-15% of people with stage two or three bowel cancer have this genetic makeup, which equates to around 2,000-3,000 cases each year in the UK.
Instead of undergoing surgery followed by three to six months of chemotherapy, participants received up to nine weeks of pembrolizumab before their bowel surgery. The researchers then continued to monitor them over time.
Personalized blood tests could guide treatment
The final phase of the ongoing trial, presented this month at the AACR in San Diego, California, was led by UCL and UCLH. University Hospital Southampton, St. James University Hospital Leeds and Christie NHS Foundation Trust Manchester also helped recruit patients and provided valuable translational samples. All translation work was carried out by UCL and biotechnology company Personalis.
Professor Marnix Jansen, clinician scientist and consultant histopathologist who is leading translational research on the trial at the UCL Cancer Institute and UCLH, said: “These results not only confirm the durability of the responses we observed almost three years ago, but also provide crucial biological insights into why immunotherapy is so effective in this setting. »
The researchers found that changes in tumor DNA in the blood closely reflected the patients’ response. The disappearance of tumor DNA from the blood was strongly associated with the absence of cancer.
Yanrong Jiang, first author of the latest abstract and a clinical PhD student at the UCL Cancer Institute, said: “As a research team, we were excited to be able to follow patients very closely using personalized blood tests. When tumor DNA disappeared from the blood, patients were much more likely to be cancer-free, and this was consistent with the long-term results we are now seeing.
“In addition, we also found that immune profiling of tumor tissues, before patients begin their first cycle of treatment, can help predict response. We hope that these tests can be used to guide treatment decisions in a more practical and timely manner.”
Patient’s history
UCLH patient Christopher Burston was diagnosed with bowel cancer in February 2023 after attending a routine screening. He had been completing mailed bowel screening kits for several years before a test came back positive.
Christopher, 73, from Portland, Dorset, said: “One came back with signs of blood in my stool. I had further tests and it was at the colonoscopy that they identified cancer in my bowel.”
A few weeks after his diagnosis, Christopher’s oncologist told him he might be eligible for the NEOPRISM clinical trial, which tested immunotherapy before surgery. Although participating meant traveling to London for treatment, he chose to enroll and was referred to UCLH.
He received three doses of immunotherapy over nine weeks before undergoing surgery in May 2023. Christopher experienced few side effects and recovered well after spending a week in the hospital.
He said: “The result of the operation was basically that the cancer had melted away, those were the doctor’s words. The immunotherapy had an almost immediate effect. I saw the images at the first colonoscopy and I could see that it was really quite a large lump. So, like I said, it wasn’t a minor thing, I was diagnosed with stage 3 cancer.”
More than three years later, Christopher is still cancer-free. He returned to his normal activities while continuing to attend his follow-up appointments regularly.
Christopher said: “The recovery went well. I had no problems. And since then I feel almost back to normal. I feel very lucky to have reached the stage where my main problem is age rather than cancer or any other illness.”
Gn Health
