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 immune-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: 0.810-0.990) 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.