Complete pathologic response after neoadjuvant immunotherapy for mismatch repair-deficient colon cancer with invading...

Mismatch repair-deficient (dMMR) colorectal cancer exhibits poor responsiveness to fluoropyrimidine-based chemotherapy but remarkable sensitivity to immune checkpoint inhibitors (ICIs). Neoadjuvant dual ICI therapy results in high pathologic response rates with minimal toxicity. However, the immunotherapy-induced rapid regression of locally advanced tumors with suspected invasion into adjacent organs may result in fistula formation. We describe here the case of an 80-year-old woman with locally advanced dMMR ascending colon cancer (cT4bN2aM0, stage IIIC), who underwent diverting ileostomy followed by neoadjuvant nivolumab plus ipilimumab therapy. Rapid tumor shrinkage resulted in the formation of a transient fistula between the ascending and transverse colon. Robotic-assisted right hemicolectomy performed 40 days after neoadjuvant therapy initiation revealed a complete pathologic response without residual carcinoma. Histopathology showed complete tumor regression with necrotic and granulomatous tissue at the invasion site, suggesting rapid fistula formation. Postoperatively, the patient developed Grade 2 immune-related pneumonitis, which resolved with corticosteroid therapy using prednisolone; no recurrence was observed six months postoperatively. This study demonstrates that neoadjuvant dual ICI therapy can achieve a complete pathologic response in locally advanced dMMR colon cancer. Preoperative diverting stoma may help reduce the risk of perforation following fistula formation resulting from rapid tumor necrosis.