Challenges presented by complete response to immune checkpoint blockade in patients with dMMR colorectal cancer: A...

Early clinical trials have demonstrated remarkable responses to immune checkpoint blockade (ICB) in patients with colorectal cancers with deficient mismatch repair (dMMR) mechanisms. The precise role immunotherapy will play in the treatment of these patients is undefined, with these agents likely to produce new challenges as well as opportunities.

A 74-year-old patient was diagnosed with a locally advanced dMMR adenocarcinoma in the transverse colon with clinical suspicion of peritoneal metastases (cT4N2M1). The burden of disease was assessed as incurable, and a referral was made for palliative oncological treatment. After 5 months of treatment with pembrolizumab, a complete radiological response in the primary tumour was seen although there was still radiological suspicion of peritoneal and lymph node metastases. The patient underwent cytoreductive surgery and hyperthermic intraperitoneal chemotherapy but unfortunately died 6 weeks later due to complications. Final histology of the surgical specimen showed no evidence of residual disease (ypT0N0M0).

This case highlights the opportunities and challenges presented by the efficacy of ICB in dMMR colorectal cancer. These agents were able to cure a patient who had disseminated disease presumed to be incurable at the time of diagnosis. However, due to current limitations in determining the degree of response to ICB, this result could only be confirmed after major surgery, which ultimately led to the patient's death.

ICB can lead to dramatic responses in patients with dMMR colorectal cancers. Major challenges remain in differentiating complete and partial responders and determining the indications for conventional surgery.