Preoperative Immunotherapy Duration and Complete Response in MMRd Colorectal Cancer

Colorectal cancer is among the most common cancers worldwide, but these tumors do not all share the same biology. In particular, microsatellite instability-high (MSI-H) or mismatch repair-deficient (MMRd) tumors can be highly sensitive to immunotherapy. How does neoadjuvant (preoperative) immunotherapy duration affect complete response rates in these tumors?

The New England Journal of Medicine published a research letter on 19 February 2025 reporting that the duration of neoadjuvant immunotherapy is directly associated with the likelihood of pathological complete response. Rousseau and colleagues analyzed data from 13 clinical trials to demonstrate the effect of treatment duration on success.

Study Details

The analysis included patients with MMRd colorectal cancer receiving PD-1 inhibitor monotherapy or a PD-1 inhibitor combined with a CTLA-4 inhibitor . Results from 13 studies showed a strong association between immunotherapy duration and clinical outcomes.

Main Findings

• In patients receiving PD-1 inhibitor monotherapy, neoadjuvant treatment lasted 1 to 7 months, with complete response rates ranging from 0% to 100%.

• Complete response rates increased significantly with treatment duration (P < 0.001; for the model fit test, P = 0.08).

• In patients receiving combined PD-1 and CTLA-4 inhibition, treatment was limited to 1.5 months or less, mainly because combination therapy increased toxicity risk.

• With combination treatment, the complete response rate after 4 weeks was 68%, and after 6 weeks was 80% .

• The researchers predict that longer treatment will increase tumor-ablative activity, meaning complete tumor elimination .

Why Does Treatment Duration Matter?

Longer neoadjuvant immunotherapy may increase complete response rates in locally advanced cancers and open the way to organ-preserving strategies.

Optimizing the duration of neoadjuvant immunotherapy may expand nonsurgical treatment options. It may also provide important information about the most effective treatment duration in adjuvant and metastatic cancer settings.

These findings help answer not only whether immunotherapy works, but how long it should be given .

Conclusion and Commentary

The study suggests that neoadjuvant immunotherapy duration could shape the future of nonsurgical treatment strategies . Longer neoadjuvant treatment may eliminate tumors more frequently and offer patients a chance to live without surgery.

However, the possible adverse effects and toxicity risks of prolonged immunotherapy require further clinical investigation. In the coming years, developing personalized immunotherapy regimens and identifying the optimal duration for each patient could mark a revolutionary step in colorectal cancer treatment.