A new approach to treating certain bowel cancers is showing long-lasting effects, say researchers, with patients remaining cancer-free for nearly three years after a short course of immunotherapy before surgery, rather than chemotherapy afterward.
The findings, from the NEOPRISM-CRC clinical trial led by researchers at University College London and University College London Hospitals (UCLH), were presented at the American Association for Cancer Research (AACR) Annual Meeting 2026 last month (17-22 April).
They expand on earlier data showing that nine weeks of preoperative treatment with pembrolizumab significantly reduced tumour size in patients with stage two or three bowel cancer.
Early outcomes showed that 59% of patients had no detectable cancer after pembrolizumab treatment and their scheduled surgery.
Durable responses and reduced recurrence
After 33 months of follow-up, none of the patients in the study has experienced a recurrence. This includes individuals with no remaining cancer after treatment as well as those with small residual traces that have not progressed or spread.
Under standard care, about 25% of patients treated with surgery followed by chemotherapy are expected to relapse within three years. These results suggest that giving immunotherapy before surgery may offer longer-lasting cancer control for this subgroup of patients.
Researchers also examined blood samples to better understand why the therapy is effective and to identify which patients are most likely to benefit. They developed personalised blood tests that can detect early signs of treatment success and determine whether any cancer remains in circulation.
Dr Kai-Keen Shiu, Chief Investigator of the trial from the UCL Cancer Institute and a Consultant Medical Oncologist at UCLH, said: “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.
“What is particularly exciting is that we now may be able to predict who will respond to the treatment using personalised blood tests and immune profiling. These tools could help us tailor our approach, identifying patients who are doing well and may need less therapy before and after surgery versus patients at higher risk of disease progression or relapse who need additional treatment.”
Bowel cancer and risk profiles
Bowel cancer is the fourth most common cancer in the UK, with about 44 000 new cases each year. While it mainly affects older adults, diagnoses in people under 50 have been rising in recent decades.
Outcomes depend heavily on how early the disease is found. Around 90% of patients with stage one bowel cancer survive at least five years. However, some subtypes respond less effectively to treatment and are more likely to return. Survival rates drop to 65% for stage three and 10% for stage four disease.
The NEOPRISM-CRC trial enrolled 32 patients with stage two or three bowel cancer that had a specific genetic profile (MMR deficient/MSI-high bowel cancer) from five hospitals across the UK. This subtype accounts for about 10%-15% of such cases, or roughly 2 000-3 000 diagnoses each year in Britain.
Participants received up to nine weeks of pembrolizumab before surgery, instead of the standard approach of surgery followed by three to six months of chemotherapy. They were then monitored over time.
The latest phase of the trial, presented at AACR in San Diego, California, was led by UCL and UCLH. Collaborating centres included University Hospital Southampton, St James’s University Hospital in Leeds, and The Christie NHS Foundation Trust in Manchester. UCL and the biotechnology company Personalis carried out the translational research.
Crucial insights
Professor Marnix Jansen, a clinician scientist and consultant histopathologist leading the trial’s translational research at UCL Cancer Institute and UCLH, said: “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.”
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 thrilled to be able to follow patients very closely using the personalised blood tests. When tumour DNA disappeared from the blood, patients were much more likely to have no cancer remaining, and this matched the long-term results we’re now seeing.
“In addition, we also saw that immune profiling from tumour tissue, before patients start their first cycle of treatment, can help to predict response. We hope these tests may be used to guide treatment decisions in a more practical and timely way.”
Study details
Neoadjuvant pembrolizumab stratified by tumour mutation burden in high-risk stage II-III dMMR/MSI colorectal cancer (NEOPRISM-CRC)
Yanrong Jiang; Anna-Maria Militello; Charles Abbott et al.
Published in Cancer Research on 15 April 2026
Abstract
Background
Patients (pts) with operable, high risk stage II-III dMMR/MSI colorectal cancer (CRC) achieved a pathological complete response (pCR) of 59% in the phase 2 NEOPRISM-CRC trial of neoadjuvant pembrolizumab (pembro). Here we report longitudinal tumour informed ctDNA dynamics and T cell receptor (TCR) clonality as a marker of treatment response, minimal residual disease, and updated survival outcomes.
Methods
A total of 32 pts with newly diagnosed radiologically node positive or high risk T3/T4 dMMR/MSI CRC received 1 cycle of pembro 200 mg IV Q3W. 31 pts with TMB-medium (6-19 mutations/Mb) or TMB-high (TMB-H) (≥20 mutations/Mb) tumors, evaluated by FoundationOne®CDx, received 2 further cycles. Surgery was performed 4-6 weeks after the final cycle. Primary endpoint was pCR. Secondary endpoints included 3-year relapse free survival, overall survival and safety. ctDNA profiling was performed using the whole genome tumor-informed Personalis NeXT Personal® assay (LOD95 of 3.45 PPM), tracking up to 1800 patient-specific variants over 11 timepoints; at baseline, prior to each cycle, pre and post-surgery, and at 3,6,9,12,24,36 months (mo) follow up. RNA-based TCR sequencing (FUME-TCRseq) was conducted on pre-treatment tumor biopsies. Unique CDR3 amino acid sequences were quantified to derive TCR repertoire metrics. Repertoires were stratified by clonotype size and compared between histopathological responders and non-responders.
Results
23/31 (74%) pts with TMB-H tumors had evaluable paired tissue and plasma samples (n=207). Baseline ctDNA was detected in all pts (23/23, 100%). Pre-surgery ctDNA clearance was strongly associated with pCR in 13/14 pts (PPV=92.9%) while persistent pre-surgical ctDNA detection predicted residual disease in 8/9 pts (NPV=88.9%). 6/6 pts who cleared ctDNA prior to cycle 2 achieved pCR (PPV=100%). All pts had undetectable ctDNA up to 24 mo post-surgery. Tumour TCR analysis demonstrated that large clonotypes (relative abundance 0.001-0.01) occupied significantly greater clonal space in pts with pCR compared with non-pCR (p=0.011). In a Bayesian model incorporating ctDNA kinetics and baseline TCR clonality, combined multimodal profiling was highly predictive of response with posterior probabilities ≥0.7 identifying pts with pCR (14/14, PPV 100%). At data cut off of 1st November 2025, median follow up was 28.7 mo (23.0-36.5) with no disease relapse.
Conclusions
Ultrasensitive longitudinal tumor-informed ctDNA monitoring may dynamically predict response to neoadjuvant immunotherapy. Expanded intratumoral TCR clonality in responders highlights the immunobiological basis of pathological response which may aid early patient stratification and guide de-escalated neoadjuvant strategies.
Cancer Research article (Open access)
See more from MedicalBrief archives:
UK review recommends earlier bowel cancer screening
Rectal cancer patients could skip radiation: US trial
No added survival benefit from chemo for younger colorectal cancer patients
Getting to the bottom of cancer rise among young people