Novel Treatment Concepts in Patients with Colorectal Carcinomas and High Microsatellite Instability

Abstract

Approximately 15% of patients with colorectal cancer show high microsatellite instability (MSI-high) in their tumour tissue. For one third of these patients, there is a hereditary cause for this finding - that leads to the diagnosis of Lynch Syndrome. In combination with clinical findings such as the Amsterdam or the revised Bethesda criteria, MSI-high status has been used as a tool in identifying patients at risk. Today, MSI-status has gained much more importance, due to its impact on treatment decisions. Patients with UICC II cancers should not receive adjuvant treatment. For patients with distant metastases and MSI-high status, immune checkpoint inhibitors can be given as first line therapy - with tremendous success. Novel data show a deep response for immune checkpoint antibodies in patients with locally advanced colon as well as rectal cancer in a neoadjuvant setting. Especially for patients with MSI-high rectal cancer, there might be a novel therapeutic regimen utilising immune checkpoint inhibitors without neoadjuvant radio-chemotherapy and even without surgery. This could lead to a relevant reduction in morbidity in this patient cohort. In conclusion, universal MSI-testing is essential for identifying patients at risk for Lynch syndrome and for optimal decision making in treatment planning.