Proposal of a novel model for identifying complete response and nonoperative management in DMMR colon cancer following neoadjuvant immunotherapy: a retrospective cohort study.

Background: The response to neoadjuvant immune checkpoint inhibition (neoICI) for mismatch repair-deficient (dMMR) colon cancer is often underestimated by radiological assessments. This study aims to develop a novel evaluation model to identify pathological complete response (pCR) and to select candidates for nonoperative management in locally advanced dMMR colon cancer following neoICI.

Materials and methods: Patients with locally advanced dMMR colon cancer who received neoICI were enrolled from two centers in Southern China. In the discovery cohort, a novel model of immun-heralding complete response (iHCR) was developed. This model was validated in a cohort from the NEOCAP trial (NCT04715633) and another observation cohort, which included patients who adopted the nonoperative management.

Results: A total of 156 patients with dMMR colon cancer who received neoICI were included. In the discovery cohort, 70 of 103 patients (67.9%) achieved pCR, although 92.9% still showed residual disease on CT scans. Negative endoscopic biopsy (P < 0.001), endoscopic tumor morphology with scar or normal mucosa (P < 0.001), and reductions of ≥50% in both tumor maximum diameter (P < 0.001) and depth (P = 0.009) were significantly correlated with pCR. The iHCR model, integrating dynamic radiological assessments, endoscopic morphology features, and biopsy results, achieved an AUC of 0.900 (95% CI, 0.810 to 0.990) in the sub-cohort with complete endoscopic and radiological information. In the validation cohort, stepwise refinement of the model further improved the AUC to 1.00. In the observation cohort (n = 32), the iHCR model predicted sustained clinical complete response with 100% concordance.

Conclusion: The iHCR model can effectively predict pCR and identify candidates for the nonoperative management in dMMR colon cancer following neoICI.