Different responses to anti-programmed cell death protein 1 (PD-1) immunotherapy in a patient with Lynch syndrome and metachronous urothelial and colon cancer: A case report

Lynch syndrome (LS), as a result of the germline mutations in DNA mismatch repair genes, is characterized by the increased risk of endometrium, colon, and urinary tract cancer. Individuals with this disorder may occasionally have multiple primary carcinomas. Regardless of tumor type, pembrolizumab was approved for the treatment of patients with unresectable or metastatic mismatch repair deficient tumors, which may be an optional therapeutic method for patients with LS with multiple primary carcinomas. This case study is of a MSH2-deficient patient with LS with metachronous urothelial and colon cancer, who received pembrolizumab treatment for 8 months. The responses of the two primary sites to immunotherapy differed. Based on the changes of tumor markers and tumor size illustrated by imageological examinations, no response was observed in the sigmoid colon lesion, whereas an immune-associated phenomenon known as pseudoprogression was detected in the ureteral lesion. Immunotherapy was innovatively applied to the patient with multiple primary carcinomas. This case proposes a novel concept in which immunotherapy may potentially control the cancer growth in patients with LS and multiple primary carcinomas. However, further large-scale investigations are required. Furthermore, it raises a challenge to monitor the effectiveness of immunotherapy.