A UK trial called NEOPRISM‑CRC gave 32 people with stage 2 or 3 MMR‑deficient/MSI‑high bowel cancer a nine‑week course of pembrolizumab before their planned surgery; after almost three years of follow‑up none have relapsed. The result suggests a path to avoid post‑operative chemotherapy for this specific genetic subgroup, but the finding is limited by sample size and by being confined to the MMR‑deficient/MSI‑high population.
NEOPRISM‑CRC: concrete results and monitoring details
The NEOPRISM‑CRC trial enrolled 32 patients across five UK hospitals and delivered pembrolizumab for nine weeks before surgery rather than following the usual pattern of surgery then chemotherapy. At the time of the report — nearly three years after treatment — zero of the 32 patients had experienced cancer recurrence. Before surgery, 59% of participants had no detectable cancer on pathological assessment, and several people who still had residual tumour at surgery remained relapse‑free.
The study also used personalised circulating tumour DNA (ctDNA) blood tests to track tumour fragments. When ctDNA disappeared during treatment, those patients were far more likely to remain disease‑free at follow‑up. That early molecular response was a stronger predictor of long‑term remission in this trial than short‑term imaging alone.
Why MMR‑deficient/MSI‑high tumours respond and who that includes
MMR‑deficient/MSI‑high tumours have a faulty DNA repair system that raises the number of mutations in cancer cells, creating more neoantigens that the immune system can recognise. Pembrolizumab blocks the PD‑1 immune checkpoint, reinvigorating T cells to attack those neoantigen‑rich tumours — a mechanism that explains the subgroup‑specific benefit seen in NEOPRISM‑CRC. In the UK this genetic subtype appears in roughly 10–15% of stage 2–3 bowel cancers, so the result is important but not applicable to most colorectal cancers.
Do not assume these outcomes apply outside MMR‑deficient/MSI‑high disease or to later stages; clinicians in the trial have been explicit about cautious interpretation and the need for larger, multicentre trials to test durability beyond the small NEOPRISM cohort.
How pre‑operative pembrolizumab compares with standard care
| Feature | NEOPRISM‑CRC: pembrolizumab before surgery | Standard: surgery then adjuvant chemotherapy |
|---|---|---|
| Timing | Nine weeks of pembrolizumab pre‑op | Surgery first; chemotherapy over months after recovery |
| Eligibility | Stage 2–3 with MMR‑deficient/MSI‑high (10–15% of cases) | Broadly used for stage 2–3 depending on risk factors |
| Relapse rate in reported data | 0% at ~3 years in 32 patients (NEOPRISM‑CRC) | About 25% relapse historically after surgery±adjuvant chemo |
| Monitoring that informed decisions | Personalised ctDNA tests during treatment | Imaging and routine pathology; less use of ctDNA so far |
| Side effects and logistics | Immunotherapy adverse events possible but many tolerated it well; in England a new injectable form cuts administration time from hours to under two minutes | Chemotherapy has predictable systemic toxicities and longer administration schedules |
| Key unknowns | Small sample (32); needs larger trials to confirm generalisability and long‑term safety | Established evidence base but quality‑of‑life and toxicity remain concerns |
Short Q&A
Who should be tested for MMR/MSI and ctDNA now? All newly diagnosed stage 2–3 colorectal cancers should receive MMR/MSI testing at diagnosis; ctDNA testing is useful where available to track response, especially if considering non‑standard pre‑op approaches.
Does ctDNA disappearance mean you can skip more treatment? In NEOPRISM‑CRC, ctDNA disappearance correlated with long‑term remission, but the evidence is still limited — decisions should be made within multidisciplinary teams and, where possible, in the context of clinical trials.
When will we know if this should replace standard care? Larger randomized trials and longer follow‑up are needed. NEOPRISM‑CRC’s nearly three‑year signal is encouraging, but regulators and guideline panels will wait for confirmatory data before changing standard pathways.
Practical decision points for patients and clinicians
If you are a patient or clinician facing stage 2–3 colorectal cancer, the immediate, actionable steps are concrete: confirm MMR/MSI status at diagnosis; discuss eligibility for trials testing neoadjuvant immunotherapy; and, if treated with pembrolizumab, use serial ctDNA as an early checkpoint to flag who might need additional therapy. These are threshold decisions rooted in measurable tests rather than subjective judgment.
Be alert to stop signals: reappearance or persistence of ctDNA after pembrolizumab, new radiological progression, or immune‑related toxicity that prevents completing planned doses. Also note system constraints — wider adoption requires guideline changes, more robust trial data, and commissioning decisions by bodies such as NHS England even though the new injectable form already shortens clinic time to under two minutes.
For now, NEOPRISM‑CRC identifies a realistic starting point — nine weeks of pre‑op pembrolizumab for MMR‑deficient/MSI‑high stage 2–3 patients with ctDNA monitoring — but it is a provisional option pending larger trials and longer follow‑up rather than an immediate universal replacement for adjuvant chemotherapy.