Researchers report 3-year colon success
- University College London and UCLH said their NEOPRISM-CRC trial kept all 32 treated stage II-III dMMR/MSI-high colorectal cancer patients relapse-free at 33 months. - Patients got nine weeks of pembrolizumab before surgery; 59% had a pathologic complete response, and ctDNA clearance tracked with the strongest outcomes. - It matters because these tumors often resist chemo, and the result pushes immunotherapy earlier — into potentially curative treatment.
Colon cancer is one of the places where immunotherapy has looked amazing in some patients and basically useless in others. The dividing line is a tumor feature called dMMR or MSI-high — a DNA-repair defect that makes the cancer much more visible to the immune system. The news here is that a UK trial called NEOPRISM-CRC just reported something unusually clean: 32 patients with high-risk stage II or III dMMR/MSI-high colorectal cancer stayed relapse-free for a median 33 months after getting pembrolizumab before surgery. ### What kind of colon cancer is this? This is not most colon cancer. It is the mismatch-repair-deficient, microsatellite-instability-high slice — roughly 10% to 15% of stage II and III bowel cancers in the UK figures the investigators used. These tumors carry lots of mutations, which makes checkpoint drugs like pembrolizumab far more likely to work than they do in mismatch-repair-proficient disease. (ucl.ac.uk) ### What did the trial actually do? NEOPRISM-CRC enrolled 32 patients across five UK hospitals. Instead of the usual sequence — surgery first, then months of chemotherapy for many patients — the team gave nine weeks of neoadjuvant pembrolizumab before surgery. The idea was simple but important: hit the intact tumor while it is still in place, when there is more cancer antigen around to train the immune system. (ucl.ac.uk) ### What were the headline results? The striking number is zero relapses at nearly three years of follow-up. Earlier readouts had already shown deep tumor shrinkage, but the updated data add durability, which is the part everyone waits for in oncology. Pathologic complete response — meaning no viable tumor found in the resected specimen — was 59%, and the median follow-up reached 33 months. (ucl.ac.uk) ### Why is zero relapse such a big deal? Because standard care is not that clean, even in this biologic subtype. The investigators said about 25% of comparable patients would be expected to recur within three years with current treatment pathways. This was a small, single-arm phase 2 study, so nobody should pretend it settles the standard of care by itself. But zero out of 32 at 33 months is the kind of signal that changes what bigger trials get built next. (ucl.ac.uk) ### What is ctDNA doing in this story? The AACR update was not just survival follow-up. The team also presented tumor-informed circulating tumor DNA data — blood tests looking for tiny fragments of residual cancer DNA after treatment. Patients whose ctDNA cleared did especially well, which hints at a future where doctors use blood-based minimal residual disease testing to decide who can safely avoid more therapy and who still needs escalation. (ucl.ac.uk) ### Does this mean surgery goes away? Not here. Unlike the famous dostarlimab rectal-cancer story, this colon-focused approach still included planned surgery. That matters because colon and rectal cancer often get discussed together, but the organ-preservation playbook is much more developed in rectal cancer than in colon cancer. NEOPRISM-CRC is really about moving immunotherapy earlier in colon cancer, not replacing surgery outright. (aacrjournals.org) ### What is the catch? The catch is selection. These were operable, high-risk stage II or III tumors with a very specific biomarker, and there were only 32 patients. Also, the field still needs randomized data to show whether pre-surgery pembrolizumab beats the best current standard, not just historical expectations. Trials like NICHE helped open this door, and NEOPRISM-CRC makes the case for walking further through it. (nejm.org) ### So what changes now? The immediate change is not that every colon cancer patient gets pembrolizumab tomorrow. The real shift is conceptual — dMMR/MSI-high colon cancer is looking less like a chemo-first disease and more like an immune-sensitive disease that may be best treated before surgery, with ctDNA helping sort who needs more afterward. If larger studies hold up, this could rewrite the curative-intent playbook for a meaningful subset of patients. (ucl.ac.uk) (nejm.org)
