Introducing Neoadjuvant Immunotherapy for Colorectal Cancer: Advancing the Frontier

OBJECTIVE: To give surgeons a review of the current and future use of neoadjuvant immunotherapy in patients with localized colorectal cancer.

BACKGROUND: Immunotherapy has revolutionized the standard of care in oncology and improved survival outcomes in several cancers. However, the applicability of immunotherapy is still an ongoing challenge. Some cancer types are less responsive to immunotherapy, and the heterogeneity in responses within cancer types is poorly understood. Clinical characteristics of the patient, the timing of immunotherapy in relation to surgery, diversities in the immune responses, clonal heterogeneity, different features of the tumor microenvironment, and genetic alterations are some factors among many that may influence the efficacy of immunotherapy.

RESULTS: In this narrative review, we describe the major types of immunotherapy used to treat localized colorectal cancer. Furthermore, we discuss the prediction of response to immunotherapy in relation to biomarkers and radiological assessment. Finally, we consider the future perspectives of clinical implications and response patterns, as well as the potential and challenges of neoadjuvant immunotherapy in localized colorectal cancer.

CONCLUSIONS: Establishing mismatch repair status at the time of diagnosis is central to the potential use of neoadjuvant immunotherapy, in particular immune checkpoint inhibitors, in localized colorectal cancer. To date, efficacy is primarily seen in patients with deficient mismatch repair status and POLE mutations, although a small group of patients with proficient mismatch repair does respond. In conclusion, neoadjuvant immunotherapy shows promising complete response rates, which may open a future avenue of an organ-sparing watch-and-wait approach for a group of patients.