Thirty-two patients with locally advanced bowel cancer received a short course of the immunotherapy drug pembrolizumab before surgery, and 59 percent of them had no detectable tumor left when surgeons operated. Updated data now show that after 33 months of follow-up, none of those patients have relapsed, according to University College London. The standard expectation for relapse in this setting is roughly one in four, making the gap between the trial result and routine care striking enough to reshape how oncologists think about treating this molecular subgroup.
Why zero relapses after pembrolizumab changes the calculus for bowel-cancer surgery
The trial in question is NEOPRISM-CRC, a UK study that gave pembrolizumab to patients whose bowel tumors carried a specific genetic signature known as mismatch-repair deficiency, or dMMR. These tumors accumulate large numbers of mutations, which makes them more visible to the immune system and, in theory, more responsive to drugs that release the brakes on immune attack. Earlier research published in the New England Journal of Medicine had already shown that PD-1 blockade works in mismatch-repair-deficient cancers, and a phase 3 trial called KEYNOTE-177 confirmed pembrolizumab’s benefit in the metastatic setting. NEOPRISM-CRC pushed the drug earlier in the treatment timeline, giving it before the tumor was removed rather than after it had already spread.
The practical question this raises is whether some patients could eventually skip surgery altogether. If a short course of immunotherapy can eliminate all visible and microscopic disease, and if a blood-based biomarker such as circulating tumor DNA can confirm that clearance, the rationale for a major abdominal operation weakens considerably. That hypothesis has not been tested in a randomized comparison, but the NEOPRISM-CRC data supply the clearest signal yet that it deserves one.
What the NEOPRISM-CRC trial measured and found
NEOPRISM-CRC, registered as NCT05197322, opened in July 2022 and enrolled 32 patients from multiple NHS Trusts across the United Kingdom. According to the UCL Cancer Trials Centre, patients received pembrolizumab for a minimum of three weeks and a maximum of nine weeks before planned surgery, with follow-up scheduled for three years. UCL’s institutional release describes the regimen as nine weeks of pre-operative pembrolizumab, though the trial’s own operational documentation specifies the three-to-nine-week window. The difference matters because it suggests clinicians had flexibility to adjust dosing duration based on individual response, and the headline figure of 59 percent with no detectable disease reflects outcomes across that range.
The initial results showed that 59 percent of patients had no signs of disease after pembrolizumab and their planned operation, according to UCL’s announcement. The updated data, covering a median of 33 months, reported zero relapses among those responders. The UCL Cancer Trials Centre separately confirmed that standard-of-care expectations for relapse in this patient group sit at around one in four, a benchmark drawn from historical surgical series where patients received conventional treatment without pre-operative immunotherapy.
The biological logic connecting these results to the broader evidence base is direct. Tumors with mismatch-repair deficiency carry a high mutational burden, which generates abnormal proteins the immune system can recognize. Pembrolizumab, a PD-1 inhibitor, blocks a checkpoint that tumors exploit to hide from immune cells. The Dutch NICHE-2 trial, published in the New England Journal of Medicine, had already demonstrated high pathological complete response rates with neoadjuvant immunotherapy in dMMR colon cancer, providing independent confirmation that the approach works in this molecular subset. NEOPRISM-CRC adds durability data: not just tumor clearance at the time of surgery, but sustained freedom from recurrence nearly three years later.
Gaps in the evidence and what to watch next
The 32-patient sample is small enough that a handful of late relapses could significantly change the percentage. Individual patient-level data on toxicity, surgical complications, and quality of life have not been deposited in a public repository or published in a peer-reviewed journal. Without those details, it is difficult to weigh the benefits of tumor clearance against the side effects of immunotherapy, which can include serious autoimmune reactions affecting the gut, liver, lungs, and endocrine system.
No head-to-head randomized trial has compared this pembrolizumab schedule against standard neoadjuvant chemotherapy or chemoradiation in dMMR colon cancer. That absence means clinicians cannot yet say with certainty that the immunotherapy-first approach is superior to existing treatment, only that the early signal is unusually strong. The three-year follow-up window specified in the trial overview will be important, because many bowel-cancer recurrences emerge within this timeframe. If the zero-relapse finding holds up through the full planned follow-up, it will further strengthen the case for rethinking standard pathways.
Another limitation is that all participants had locally advanced, but not widely metastatic, disease. The biology and immune contexture of early-stage tumors can differ from those of cancers that have already spread, so the NEOPRISM-CRC results cannot simply be extrapolated to every patient with dMMR colorectal cancer. Likewise, the trial was conducted within the UK National Health Service, where multidisciplinary teams and centralized pathology review may support consistent implementation of biomarker testing and neoadjuvant therapy in ways that could be harder to replicate in more fragmented health systems.
There is also the question of how best to select patients for a possible non-operative strategy. Even among dMMR tumors, responses to immunotherapy are not uniformly complete. Some patients in NEOPRISM-CRC still had residual disease at the time of surgery, underscoring that checkpoint blockade is not a guaranteed cure. Future studies are likely to incorporate circulating tumor DNA, advanced imaging, and perhaps even repeat biopsies to better identify who can safely delay or omit surgery and who still requires immediate resection despite a radiographic response.
Implications for patients and health systems
If further research confirms that a subset of patients can avoid major surgery after neoadjuvant pembrolizumab, the implications would extend beyond oncology. Bowel-cancer operations can carry substantial risks of infection, anastomotic leak, and long-term changes in bowel function. For some patients, especially those with tumors in the rectum, surgery can mean a permanent stoma. An effective non-surgical pathway would therefore not only improve cancer outcomes but also reduce the burden of treatment-related disability.
From a health-system perspective, shifting part of the treatment burden from operating theatres to infusion suites would require reallocation of resources, but it might also free surgical capacity for patients whose tumors are not amenable to immunotherapy. Cost-effectiveness analyses will need to account for the high price of checkpoint inhibitors alongside potential savings from fewer operations, shorter hospital stays, and reduced need for adjuvant chemotherapy.
For now, experts involved in NEOPRISM-CRC are urging caution as well as optimism. The trial’s chief investigators, including oncologist Kai-Keen Shiu, have emphasized that pembrolizumab before surgery should still be considered experimental outside clinical trials. They highlight the need for robust multidisciplinary decision-making, careful patient counselling about uncertainties, and systematic collection of long-term outcomes.
As larger studies open and more mature data accumulate, the field will be watching several key endpoints: sustained relapse-free survival, overall survival, late toxicities, and patient-reported quality of life. Regulators and guideline committees will also look for evidence that any move toward organ preservation does not inadvertently increase the risk of undertreating aggressive disease. The NEOPRISM-CRC experience shows what is possible when a well-chosen biomarker and a potent immunotherapy intersect at the right point in the treatment journey. The challenge now is to confirm, refine, and safely extend those gains without losing sight of the individual patients behind the percentages.
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*This article was researched with the help of AI, with human editors creating the final content.
