Current Status of the Diagnosis and Treatment of Mismatch Repair Deficient Colorectal Cancer

Colorectal cancer remains a leading cause of morbidity and mortality worldwide with diverse pathways of carcinogenesis. Deficiencies in the DNA mismatch repair and resultant microsatellite instability are thought to make up roughly 15% of localized and 5% of metastatic cancers of the colon and rectum. Cancers arising through this pathway are characterized by poor response to traditional chemotherapies, but have demonstrated unprecedented responses to immunotherapy over the last decade. Thus, the management of mismatch repair-deficient/microsatellite-unstable colorectal cancer is a rapidly evolving field. In this review we provide a clinician-oriented update on the diagnosis and management of mismatch repair-deficient/microsatellite-unstable colorectal cancer. We explore the tools used for diagnosis as well as the causes and implications of the failure of these tools, along with practical recommendations to mitigate and circumvent such errors. Furthermore, we examine the changing treatment paradigm in the advanced setting with the implementation of mono and dual immunotherapy approaches and explore who is most likely to benefit from such strategies, and how to address treatment failures. Finally, we explore how immunotherapy may allow for non-surgical approaches in the localized setting and discuss the evolving evidence for neoadjuvant and adjuvant approaches when surgery is used.