Thirty-two colon cancer patients stayed cancer-free for nearly three years after just nine weeks of immunotherapy, skipping harsh chemotherapy entirely.
Story Highlights
- NEOPRISM-CRC trial treated stage 2/3 dMMR/MSI-high patients with preoperative pembrolizumab, achieving 59% pathological complete response.
- Zero recurrences at 33 months versus 25% relapse rate with standard surgery plus chemo.
- ctDNA monitoring predicted outcomes, clearing in all non-relapsing cases.
- Leads shift from 6-month adjuvant chemo to short neoadjuvant immunotherapy for this 12-15% of cases.
- Presented at AACR 2026; echoes MSKCC’s 100% response in similar rectal trial.
NEOPRISM-CRC Trial Delivers Zero Recurrences
UCL and UCLH researchers enrolled 32 patients with stage 2/3 MMR-deficient colorectal cancer across five UK hospitals starting in 2023. They administered nine weeks of pembrolizumab before surgery. Surgeons found no detectable cancer in 59% of cases. All 32 patients remained cancer-free at 33-month follow-up in April 2026. This outperformed standard care’s 25% relapse rate.
Pembrolizumab Targets Hypermutated Tumors
dMMR/MSI-high tumors, affecting 12-15% of localized colorectal cancers, feature DNA repair defects creating high neoantigen loads. Pembrolizumab, FDA-approved for advanced MSI-H cancers since 2017, unleashes T-cells against these markers. NEOPRISM-CRC applied it neoadjuvantly, shrinking tumors pre-surgery. Patients avoided postoperative chemo, reducing neuropathy and other toxicities common in FOLFOX or CAPOX regimens.
ctDNA Emerges as Precision Predictor
PhD student Yanrong Jiang analyzed circulating tumor DNA, which cleared in patients achieving pathological complete response. This biomarker matched long-term results, enabling real-time efficacy checks. Chief investigator Dr. Kai-Keen Shiu called results “extremely encouraging and safe.” Prof. Marnix Jansen highlighted tumor microenvironment changes driving durability. Such tools personalize monitoring beyond imaging.
Precedents from MSKCC and NICHE Trials
Memorial Sloan Kettering’s 2022 dostarlimab trial yielded 100% complete responses in 42 MMR-deficient rectal cancer patients, with no recurrences up to four years. NICHE-2 showed 67% pathological complete response using nivolumab plus ipilimumab. These validate neoadjuvant immunotherapy for MSI-high colorectal cancers. NEOPRISM-CRC extends this to colon, using single-agent pembrolizumab from Merck.
Colon cancer breakthrough keeps patients cancer-free for nearly 3 years
A short burst of immunotherapy before surgery is delivering surprisingly powerful results for a specific type of colorectal cancer. Patients in a UK-led trial who received just nine weeks of pembrolizumab…
— The Something Guy 🇿🇦 (@thesomethingguy) May 6, 2026
Paradigm Shift Challenges Standard Chemo
Stage III colon cancer typically demands 3-6 months of adjuvant FOLFOX or CAPOX post-surgery, cutting recurrence by one-third but causing toxicity. Low-risk patients now get 3 months; high-risk stick to 6. NEOPRISM-CRC’s 0% relapse suggests preoperative immunotherapy could supplant this for dMMR cases, halving mortality in 200,000 global patients yearly. Patient preferences will guide adoption.
Future Approvals and Equity Concerns
Trial completion spurs phase 3 plans like NRG-GI008. Oncologists anticipate NCCN/ESMO guideline updates, accelerating FDA/EMA nods akin to dostarlimab’s 2024 breakthrough status. Merck eyes revenue growth from expanded Keytruda use. Yet small cohort size demands caution; MSI-testing access lags in underserved areas.
Sources:
Breakthrough Bowel Cancer Trial Leaves Patients Cancer-Free for Nearly 3 Years
Patients remain cancer-free nearly 3 years after receiving experimental immunotherapy
Rectal cancer disappears after experimental use of immunotherapy
Breakthrough Bowel Cancer Trial Leaves Patients Cancer-Free for Nearly 3 Years
