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.