A British clinical trial has delivered results in colorectal cancer that are rare in oncology: 59 percent of patients with a genetically defined form of the disease had no living tumor remaining in their body after nine weeks of immunotherapy before surgery. Over a follow-up period of nearly three years, not one of the 32 study participants relapsed. That is extraordinary for colorectal cancer. The current standard chemotherapy achieves complete remission in only seven percent of patients in this subgroup, and around 25 percent experience a relapse within three years.
What Makes dMMR Colorectal Cancer Different
Not all colorectal cancers respond the same way to treatment. Around 15 percent of all cases carry a genetic defect in a DNA error-correction system known as Mismatch Repair, abbreviated dMMR (deficient Mismatch Repair). Tumors with this defect also display the characteristic MSI-H (Microsatellite Instability High). Without the repair system, mutations accumulate in tumor cells at an unusually fast rate. For immunotherapy, that is an advantage: a tumor carrying many mutations offers many targets that the immune system can recognize and attack.
Worldwide, colorectal cancer is one of the most common cancers, with around 1.9 million new cases diagnosed annually according to the World Health Organization. At a dMMR prevalence of roughly 15 percent, approximately 285,000 patients per year globally could potentially benefit from findings like those in this study. The problem with current standard therapy: FOLFOX, a chemotherapy combination of 5-fluorouracil, oxaliplatin, and leucovorin, performs particularly poorly against dMMR tumors. The FOxTROT trial documented a pathological complete remission rate of only seven percent in this subgroup.
How NEOPRISM-CRC Was Designed
The study ran across five British hospitals. Thirty-two patients with stage II and III dMMR colorectal cancer received nine weeks of pembrolizumab before their planned surgery, instead of the standard chemotherapy typically given after the operation. Pembrolizumab (brand name Keytruda) is a monoclonal antibody that blocks the PD-1 receptor on T-cells. Tumor cells exploit this receptor to suppress the immune system. When pembrolizumab releases that brake, the body's own defense cells can attack the tumor again.
Fifty-nine percent of patients achieved a pathological complete remission: surgeons found no living tumor when they operated. Severe immune reactions (grade 3 or 4 by clinical classification) occurred in 6.2 percent of patients, corresponding to two of the 32 participants. Researchers presented the results at the AACR Annual Meeting 2026 in San Diego in April. The long-term outcome, covering 33 months of follow-up, was described by eCANCER, the European cancer research journal, as particularly remarkable.
Zero Relapses in 33 Months
The decisive result is the long-term finding. After a median follow-up of 33 months, not a single patient had relapsed, neither among those with complete remission nor among those who still had residual tumor detectable after immunotherapy. The study authors interpret this as evidence of lasting immunological protection: pembrolizumab does not merely reactivate circulating T-cells but trains them specifically against the tumor. Even after surgery, primed immune cells can continue to recognize and eliminate any remaining tumor tissue, according to the hypothesis.
How Earlier Breakthroughs Began
Transformative therapies have often started as small trials. With hepatitis C, direct-acting antivirals (DAAs) fundamentally changed treatment from 2014 onward: a disease that had been fought for decades only with side-effect-heavy interferon became curable in over 95 percent of patients. Phase II data were compelling; regulatory approval followed quickly.
In HIV, the introduction of triple combination therapy in 1996, tested in clinical trials with a few hundred patients, completely reversed the prognosis. Today, life expectancy for people living with HIV on therapy is nearly identical to the general population. A similar shift would be conceivable for dMMR colorectal cancer if larger trials confirm the effects seen in NEOPRISM-CRC. Both comparisons show the same pattern: a mechanism that works, proven small, confirmed large.
Three Conditions Before Standard of Care
For neoadjuvant pembrolizumab to become standard treatment for dMMR colorectal cancer, three things must come together. First, a randomized Phase III trial with several hundred patients is needed. NEOPRISM-CRC enrolled 32 patients, with a planned total recruitment of 78. Second, the FDA and EMA would need to approve based on this evidence, which following a Phase II study means a more demanding path. Third, the cost question: pembrolizumab is priced at tens of thousands to over $100,000 per year of therapy depending on country and indication.
The study authors explicitly recommend a follow-up trial and clearly state the limits of their data: the sample size is too small for definitive conclusions, and follow-up must be extended, since colorectal cancer is medically considered durably cured only after five years. The direction is unusually unambiguous. The evidence base is still being built.