Nine Weeks of Immunotherapy Before Surgery Leaves Every Bowel Cancer Patient Relapse-Free After 33 Months in NEOPRISM-CRC Trial
A UK trial of preoperative pembrolizumab for MMR-deficient colorectal cancer shows zero relapses across all 32 patients after nearly three years of follow-up.
Overview
A small but striking clinical trial has kept every one of its participants free of cancer recurrence for nearly three years — an outcome that researchers say could reshape how a specific subset of bowel cancer is treated. The NEOPRISM-CRC trial, led by investigators at University College London and University College London Hospitals, replaced standard post-operative chemotherapy with nine weeks of the immunotherapy drug pembrolizumab administered before surgery. At a mean follow-up of 33 months, none of the 32 enrolled patients had relapsed, according to results presented at the American Association for Cancer Research Annual Meeting 2026 in San Diego in April and reported by ScienceDaily and UCL News.
What We Know
The trial enrolled patients with stage two or three bowel cancer carrying a specific genetic signature: mismatch repair deficiency, also described as microsatellite instability-high (MMR deficient/MSI-high). This subtype accounts for 10 to 15 percent of stage two and three bowel cancer cases, representing approximately 2,000 to 3,000 diagnoses per year in the United Kingdom, where bowel cancer is the fourth most common cancer with around 44,000 new cases annually, as reported by SciTechDaily and ecancer.
Participants received three cycles of intravenous pembrolizumab 200 mg — a treatment period of up to nine weeks — before their planned surgical procedure, replacing the chemotherapy that typically follows surgery in current standard care. The trial recruited from five UK hospitals: UCLH, University Hospital Southampton, St. James’s University Hospital Leeds, and Christie NHS Foundation Trust Manchester, per UCL News.
Initial results had already shown that 59 percent of patients achieved a pathologic complete response — meaning no detectable cancer remained — after treatment and surgery. The 33-month follow-up data, first author Yanrong Jiang, a clinical PhD student at UCL Cancer Institute, presented at AACR 2026, confirmed that this response has proved durable: all 32 patients remain alive and relapse-free. By comparison, approximately 25 percent of patients with this cancer type who receive standard surgery plus post-operative chemotherapy relapse within three years, as noted by Medical Xpress and UCL News.
The trial also tracked circulating tumor DNA (ctDNA) — fragments of cancer-derived genetic material in the blood — as a real-time measure of treatment response. At baseline, ctDNA was detectable in 25 of 25 patients tested. After the first cycle of pembrolizumab, 24 percent had undetectable ctDNA; after the second cycle, 43 percent; after the third, 58 percent; and after surgery, 100 percent had undetectable levels, according to Inside Precision Medicine.
The research team also identified distinct molecular responder subgroups based on the pace at which ctDNA cleared. Super molecular responders — 6 patients — achieved 100 percent pathologic complete response. Dynamic molecular responders — 11 patients — achieved 82 percent pCR. Poor molecular responders — 8 patients — achieved 0 percent pCR, per Inside Precision Medicine.
“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,” said Dr. Kai-Keen Shiu, the trial’s Chief Investigator and a Consultant Medical Oncologist at UCLH, as quoted by ScienceDaily.
Shiu added: “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.”
Professor Marnix Jansen, clinician scientist and consultant histopathologist at UCL Cancer Institute and UCLH, noted that the findings “not only confirm the durability of responses we saw almost three years ago, but also provide crucial biological insights,” according to ScienceDaily.
One patient, Christopher Burston, a 73-year-old from Portland, Dorset diagnosed in February 2023, described the experience to SciTechDaily: “The outcome of the surgery was essentially that the cancer had melted away.” Burston added that he now feels “very lucky” that his “main problem is age rather than cancer or any illness.”
What We Don’t Know
The NEOPRISM-CRC trial enrolled 32 patients, which is too small to draw definitive conclusions about efficacy or broader applicability. The results have not yet been published in a peer-reviewed journal — the data presented at AACR 2026 represent conference abstracts, and independent replication across larger populations is still required.
It also remains unclear whether patients who did not achieve a pathologic complete response — particularly the eight classified as poor molecular responders — will eventually experience relapse, and at what rate. The 33-month follow-up, while encouraging, does not span the full window during which bowel cancer typically recurs.
Finally, the 10 to 15 percent of patients with stage two or three bowel cancer who carry the MMR-deficient/MSI-high profile would be the intended beneficiaries of this approach; the remaining 85 to 90 percent of patients with different genetic profiles would not be expected to respond similarly to pembrolizumab monotherapy.
Analysis
The NEOPRISM-CRC results are notable for several reasons. A 0 percent recurrence rate at 33 months — compared with roughly 25 percent under standard care — represents a substantial gap, even accounting for the small sample size. The ctDNA-based stratification into molecular responder groups also points toward a potential framework for patient selection: if blood-based biomarkers can reliably identify who will achieve a pathologic complete response before surgery, it may become possible to tailor treatment intensity accordingly, sparing some patients from surgery while escalating care for poor responders.
The MMR-deficient/MSI-high subtype has previously been identified as responding well to PD-1 checkpoint inhibitors like pembrolizumab in the metastatic setting. NEOPRISM-CRC extends that observation to earlier-stage, operable disease, and into the preoperative window — a context where removing the tumor before immune responses are fully active has traditionally been the standard approach.
Bowel cancer carries sharply divergent prognoses by stage: five-year survival is approximately 90 percent for stage one, 65 percent for stage three, and only 10 percent for stage four, per SciTechDaily. Interventions that keep stage two or three patients out of the stage four category are therefore of significant clinical and social value. The path from a 32-patient pilot to a standard-of-care recommendation will require larger randomized trials, but the durability of responses seen in NEOPRISM-CRC gives investigators a strong rationale to design them.