Clinical metric of tumor mutational burden depicts colorectal cancer patients at the extremes

Purpose Rare cases of colorectal cancer patients with exceptionally good or poor prognosis often remain overlooked, limiting insights into prognostic factors and underlying mechanisms. Methods This study developed an analytical framework to investigate cancer patients at the extremes using tumor mutational burden (TMB). By analyzing data from 1277 colorectal cancer patients who did not receive immunotherapy, this analysis assessed how patient survival varies with a broad range of TMB levels. Results Among patients with TMB <= 10 mutations per megabase (mut/Mb), increasing TMB was associated with worse survival outcomes. In contrast, patients with TMB > 10 mut/Mb showed increasingly improved survival. Notably, a small subgroup (3.83%) with TMB > 60 mut/Mb had significantly better survival outcomes. Conclusions These findings highlight TMB's dual role in colorectal cancer progression. This study suggests that atypical patients can coexist within the same "disease continuum" with typical patients, under the universal context unified by a shared cancer hallmark. TMB provides a useful biomarker for identifying these extremes, offering a clinical metric to better predict patient outcomes and personalize treatment strategies.