Tumor mutational burden in colorectal cancer: Implications for treatment

Abstract

Although immune checkpoint inhibitors have revolutionized the treatment of several advanced solid cancers, in colorectal cancer, the transformative benefit of these innovative medicines is currently limited to those with deficient mismatch repair or high microsatellite instability. Tumor mutational burden (TMB) has emerged as a potential predictor of immunotherapy benefit, but the lack of standardization in its assessment and reporting has hindered the introduction of this biomarker in routine clinical practice. Here, we compiled 45 colorectal cancer studies utilizing numerical thresholds for high-TMB. In this group of studies, TMB cut-offs ranged from 6.88 to 41 mut/Mb and were most often set at 10, 17, or 20 mut/Mb. Additionally, we observed divergent TMB definitions and inconsistent disclosure of specific methodological details, which collectively emphasize the substantial lack of harmonization within the field. Ongoing efforts to harmonize TMB assessment will be critical to validate TMB as a predictive marker of immunotherapy response. • TMB application in routine practice has faced meaningful methodological challenges. • We compiled the TMB definition, methodology, and cut-off used in 45 studies. • Cut-offs ranged from 7 to 41 mut/Mb and were most often set at 10, 17 or 20 mut/Mb. • Our dataset confirms the lack of standardization and clarity reported by others. • Current evidence is currently not sufficient to recommend the use of TMB in colorectal cancer.

Topics & Concepts