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

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. In mismatch repair-deficient cancer, cells cannot repair errors in DNA well, causing many different genetic errors to build up. These cancers often show strong changes in their immune characteristics.

Here, we present the case of an 80-year-old woman with advanced mismatch repair-deficient cancer in the ascending colon, The cancer was also suspected of having spread to the transverse colon, located nearby. A treatment called immune checkpoint inhibitor (ICI) therapy can often effectively shrink tumors in patients with mismatch repair-deficient bowel cancer.

However, in severe cases with tumors that are suspected of spreading, the fast reduction caused by ICI therapy may create a hole in the bowel, known as a fistula. In this case, doctors first performed surgery on the patient to redirect waste from the colon to an external pouch (stoma), before the ICI therapy was started. The treatment successfully got rid of the invasive cancer cells and the fistula that formed later healed. This diverting surgery, performed prior to ICI therapy, likely helped reduce the risk of bowel leakage and infection at the site of the fistula.

Therefore, diverting waste material may be helpful in patients with similar types of colon cancer suspected of invading nearby organs. We recommend that doctors should carefully consider this option in the future.