TOKYO —

Patients diagnosed with a specific, aggressive form of bowel cancer have achieved a significant milestone, remaining free of recurrence for nearly three years following a short preoperative course of immunotherapy. These groundbreaking findings emerge from the NEOPRISM-CRC clinical trial, a collaborative effort spearheaded by researchers at University College London (UCL) and University College London Hospitals (UCLH). The results, poised for presentation at the American Association for Cancer Research (AACR) Annual Meeting 2026 in April, build upon earlier promising data from the trial, which initially demonstrated substantial tumor reduction in individuals with stage two or three bowel cancer treated with the immunotherapy drug pembrolizumab prior to surgery.

The initial findings from the NEOPRISM-CRC trial revealed a remarkable response rate, with 59% of patients exhibiting no detectable signs of disease following a nine-week course of pembrolizumab and subsequent bowel cancer surgery. This innovative neoadjuvant approach, administering treatment before surgical intervention, represents a significant departure from traditional treatment paradigms, offering a beacon of hope for those facing a particularly challenging diagnosis.

Zero Bowel Cancer Recurrences After 33 Months: A Paradigm Shift

The extended follow-up data from the NEOPRISM-CRC trial is nothing short of transformative. After an average of 33 months of observation, an astonishingly high proportion of patients, across both those who achieved complete remission post-treatment and those with residual disease, have experienced no return of their cancer. Critically, in the latter group, any remaining cancer cells did not proliferate or spread during the follow-up period, suggesting a profound and durable anti-cancer effect.

This outcome stands in stark contrast to the standard treatment approach for similar stages of bowel cancer, which typically involves surgery followed by adjuvant chemotherapy. Under the conventional regimen, approximately 25% of patients are expected to experience a relapse within a three-year timeframe. The NEOPRISM-CRC trial’s findings strongly suggest that the strategic administration of a short course of immunotherapy before surgery could offer a superior and more enduring form of cancer control for this specific patient cohort.

Unlocking the Secrets: Personalized Blood Tests and Immune Profiling

In parallel with tracking patient outcomes, researchers delved into the biological underpinnings of this remarkable success. Extensive analysis of blood samples was conducted to elucidate the mechanisms driving the treatment’s efficacy and, crucially, to identify biomarkers that could predict which patients are most likely to benefit. This deep dive has led to the development of sophisticated, personalized blood tests designed to offer early indications of treatment response and to detect the presence of circulating tumor DNA (ctDNA), a key indicator of residual disease.

Dr. Kai-Keen Shiu, Chief Investigator of the NEOPRISM-CRC trial, affiliated with the UCL Cancer Institute and a Consultant Medical Oncologist at UCLH, expressed profound optimism about the findings. "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," Dr. Shiu stated.

He further elaborated on the potential of predictive tools: "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. 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." This personalized approach has the potential to revolutionize treatment strategies, moving away from a one-size-fits-all model towards precision medicine.

Understanding Bowel Cancer: Incidence, Stages, and Survival

Bowel cancer, also known as colorectal cancer, remains a significant public health challenge. In the United Kingdom, it ranks as the fourth most common cancer, with an estimated 44,000 new diagnoses annually. While historically more prevalent in older adults, concerning trends indicate a rise in incidence among individuals younger than 50 in recent decades.

The prognosis for bowel cancer is intrinsically linked to the stage at which it is detected. Early diagnosis dramatically improves outcomes, with approximately nine in ten individuals diagnosed with stage one bowel cancer surviving for at least five years. However, the landscape shifts considerably for more advanced stages or for specific tumor subtypes that exhibit less responsiveness to conventional therapies. For stage three bowel cancer, five-year survival rates decrease to approximately 65%, and for stage four disease, this figure drops to a stark 10%.

The NEOPRISM-CRC trial specifically focused on a subset of patients with stage two or three bowel cancer possessing a particular genetic profile: microsatellite instability-high (MSI-high) or mismatch repair deficient (dMMR). This genetic characteristic, found in approximately 10-15% of patients with stage two or three bowel cancer, translates to an estimated 2,000 to 3,000 cases annually in the UK. These individuals often have a poorer prognosis with standard treatments, making them ideal candidates for exploring novel therapeutic avenues.

The NEOPRISM-CRC Trial Design: A Preoperative Immunotherapy Approach

The NEOPRISM-CRC trial enrolled 32 patients across five leading hospitals in the UK. These participants, all diagnosed with stage two or three MSI-high/dMMR bowel cancer, deviated from the conventional treatment pathway. Instead of immediate surgery followed by three to six months of chemotherapy, they received up to nine weeks of pembrolizumab, a type of immunotherapy known as a checkpoint inhibitor, administered before their scheduled bowel surgery. This neoadjuvant strategy allowed researchers to assess the drug’s impact on the tumor in its original location and to monitor patient responses closely over an extended period.

Advancements in Translational Research: Guiding Future Therapies

The latest phase of the ongoing NEOPRISM-CRC trial, presented at the AACR meeting in San Diego, California, highlighted significant progress in translational research. This critical component of the study, led by UCL and UCLH, involved comprehensive analysis of biological samples to understand treatment mechanisms and identify predictive markers. Collaborating institutions included University Hospital Southampton, St. James’s University Hospital in Leeds, and The Christie NHS Foundation Trust in Manchester, which played vital roles in patient recruitment and the supply of valuable translational samples. The sophisticated laboratory work was meticulously conducted by teams at UCL and the biotechnology company Personalis.

Professor Marnix Jansen, a clinician scientist and consultant histopathologist at the UCL Cancer Institute and UCLH, who is leading the translational research, underscored the significance of these insights. "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," Professor Jansen commented.

Key findings from the translational research revealed a strong correlation between the changes in tumor DNA detected in the bloodstream and a patient’s response to treatment. Specifically, the disappearance of ctDNA from the blood was a powerful predictor of complete tumor eradication and favorable long-term outcomes.

Yanrong Jiang, the first author of the abstract presented at AACR and a clinical PhD student at the UCL Cancer Institute, shared her team’s excitement: "As a research team, we were thrilled to be able to follow patients very closely using the personalized blood tests. When tumor 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."

Furthermore, the research indicated that immune profiling of tumor tissue, performed before the commencement of any treatment, could also serve as a valuable tool for predicting treatment response. "In addition, we also saw that immune profiling from tumor tissue, before patients start their first cycle of treatment, can help to predict response," Jiang added. "We hope these tests may be used to guide treatment decisions in a more practical and timely way." The integration of these predictive tools holds the promise of enabling clinicians to make more informed and individualized treatment decisions, potentially sparing some patients unnecessary toxicity and ensuring others receive the most aggressive and effective therapies.

A Patient’s Perspective: Christopher Burston’s Journey

The profound impact of this innovative treatment is perhaps best illustrated by the personal story of Christopher Burston, a 73-year-old patient treated at UCLH. Christopher’s journey began in February 2023 when a routine bowel screening kit revealed the presence of blood in his stool, prompting further investigation that led to the diagnosis of bowel cancer.

Upon learning of his diagnosis, Christopher was informed that he might be eligible for the NEOPRISM-CRC clinical trial, which was exploring the efficacy of immunotherapy prior to surgery. Despite the necessity of traveling to London for treatment, Christopher opted to enroll in the trial, recognizing the potential benefits of this novel approach.

Over a nine-week period, Christopher received three doses of pembrolizumab. He reported experiencing minimal side effects and a smooth recovery following his surgery in May 2023. Reflecting on the impact of the treatment, Christopher described his surgeon’s observation: "The outcome of the surgery was essentially that the cancer had melted away, these were the doctor’s words. The immunotherapy had had an almost immediate effect." He recalled seeing images from his initial colonoscopy, which revealed a substantial tumor, underscoring the aggressive nature of his stage three cancer.

More than three years later, Christopher remains cancer-free, actively engaged in his normal life, and continues with regular follow-up appointments. "The recovery went fine. I didn’t have any problems. And since then, I’ve been feeling pretty much back to normal," he shared. "I feel very lucky that I’ve reached the stage where my main problem is age rather than cancer or any illness." His experience serves as a powerful testament to the life-changing potential of this pioneering treatment.

Broader Implications and Future Directions

The NEOPRISM-CRC trial’s findings have far-reaching implications for the management of MSI-high/dMMR bowel cancer. This study not only demonstrates the efficacy of neoadjuvant pembrolizumab but also highlights the growing importance of personalized medicine in oncology. The ability to predict treatment response through blood tests and immune profiling could revolutionize clinical decision-making, enabling clinicians to optimize treatment strategies for individual patients.

The success observed in this specific subgroup of bowel cancer patients may pave the way for similar investigations in other cancer types that share the MSI-high/dMMR molecular profile. Continued research into the mechanisms of immunotherapy response, coupled with the development of even more precise predictive tools, holds the key to unlocking further advancements in cancer treatment and improving outcomes for a wider patient population. The NEOPRISM-CRC trial represents a significant stride forward in the ongoing battle against bowel cancer, offering renewed hope and a glimpse into a future where cancer treatment is more effective, less toxic, and tailored to the individual.