Colorectal cancer, describing cancer that starts in the colon or the rectum, is the third most common cancer worldwide, and the second leading cause of cancer-related deaths worldwide.
Surgery is the most common treatment for colon cancer. Often, people may receive chemotherapy prior to the surgery, known as neoadjuvant therapy, to help shrink the tumor, make it easier to remove, and help with bowel control.
However, while neoadjuvant chemotherapy can be an effective option, it does not work equally well for everyone.
A certain genetic profile, known as MMR-deficient/MSI-high colon cancer, accounts for roughly 15% of those with stage 2 to 3 colon cancer.
Research suggests this type of colon cancer is less responsive to chemotherapy, and growing evidence indicates that immunotherapy may produce longer-lasting responses and better survival than standard chemotherapy for many patients.
Now, a clinical trial led by researchers at University College London (UCL), in the United Kingdom, suggests that a short course of immunotherapy given before surgery could significantly improve outcomes for those with MMR-deficient/MSI-high colon cancer.
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The findings, presented at the American Association for Cancer Research Annual Meeting 2026, suggest that this approach may challenge the current standard of care, and potentially reduce the need for chemotherapy in certain patients.
In the NEOPRISM-CRC trial, the UCL researchers tested the immunotherapy drug pembrolizumab in 32 patients with stage 2 or 3 colorectal cancer and the MMR-deficient/MSI-high genetic profile.
Instead of receiving the usual treatment of surgery followed by 3 to 6 months of chemotherapy, participants were given 9 weeks of immunotherapy before their operations.
The initial trial results indicated that 59% of patients had no signs of cancer after treatment with pembrolizumab and their planned operation. After 33 months of follow-up, none of the treated patients experienced cancer recurrence.
This included both those who had no signs of cancer after treatment, and those who still had small amounts remaining, which did not progress or spread during follow-up.
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By comparison, approximately a quarter of patients with stage 3 colon cancer treated with standard surgery plus chemotherapy experience recurrence, most often within the first 3 years.
Marnix Jansen, MSc, MD, PhD, a clinician scientist and consultant histopathologist who is leading the translational research on the trial from UCL Cancer Institute and University College London Hospitals NHS Foundation Trust explained the importance of the findings to Medical News Today.
“NEOPRISM-CRC tested a short course of pembrolizumab immunotherapy before surgery in patients with stage III and so-called high-risk stage II bowel cancer whose tumours are MMR-deficient/MSI-high. In the reported cohort of 32 patients, 59% had no detectable cancer after immunotherapy and surgery, and after a median follow-up of about 33 months, none had relapsed,” Jansen told us.
“This is clinically important because this tumour subtype affects about 10 to 15% of stage II to III bowel cancers, and the usual pathway often involves surgery followed by months of chemotherapy.”
– Marnix Jansen, MSc, MD, PhD
Immunotherapy helps the immune system recognize and attack cancer cells more effectively. Earlier research suggests that immunotherapy may be highly effective for many patients with MMR deficient/MSI-high colorectal cancer and can lead to durable, long-lasting responses.
Immunotherapy is likely effective against MMR-deficient/MSI-high colorectal cancer as these tumors contain genetic variations that produce abnormal proteins, known as neoantigens, that make them highly visible to the immune system.
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These tumors are typically able to use immune checkpoints to prevent the immune system from destroying them. However, checkpoint inhibitors, such as pembrolizumab, can block this and enable the immune system to attack the cancer cells.
“Before surgery, the tumour is still present, which means the immune system can ‘see’ a large amount of cancer material,” Jansen told MNT.
“Immunotherapy may therefore train and amplify an anti-cancer immune response while the tumour and its local immune environment are intact. The trial rationale also notes evidence from other cancers that checkpoint inhibitors given before surgery can produce stronger local and systemic anti-tumour responses than surgery alone.”
Additionally, the researchers used personalized blood tests to track tumor DNA in the bloodstream.
These tests could help clinicians tailor their approach by identifying those who are responding well and may need less therapy before and after surgery, and those at higher risk of progression or relapse who may require additional treatment.
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Jansen notes that these personalized blood tests could be “potentially very useful.”
“These ultrasensitive tests can look for tiny traces of tumour DNA in the blood. In NEOPRISM-CRC, when tumour DNA disappeared from the blood after immunotherapy, patients were very likely to have no cancer remaining,” he added.
“In practice, this could help doctors identify patients doing well who may need less treatment, and patients at higher risk who may need closer monitoring or additional therapy,” the researcher told us.
The findings from this trial suggest a possible shift in treatment for some patients. Instead of receiving chemotherapy after surgery, individuals may receive immunotherapy before surgery, with less or no chemotherapy afterwards. This could help reduce treatment burden and side effects, while improving long-term outcomes.
“Yes, that is one of the key implications — but it should be phrased cautiously,” Jansen said when MNT asked if these findings suggest reductions in chemotherapy for some patients.
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“These findings support a possible shift toward biomarker-led, pre-operative immunotherapy for selected MMR-d/MSI-H bowel cancers, with the possibility that some patients may avoid or reduce post-operative chemotherapy and even surgery.”
“However, NEOPRISM-CRC is a phase II trial, recruitment is ongoing/targeted at 78 patients, and the primary endpoint is 3-year relapse-free survival, so larger and longer-term data will be important before this becomes a broad standard of care,” he added.
However, despite the encouraging results, the study was relatively small, involving 32 patients. Thus, larger trials will be necessary to confirm the findings and determine whether they apply more broadly.
The researchers are also continuing to refine tools, such as blood-based tumor DNA tests, to better personalize treatment decisions.
While more research is needed, a short, preoperative course of immunotherapy may offer long-lasting protection and could mark an important step toward more targeted, less intensive colorectal cancer care.
