Limitations of Existing Markers
The Colon Recurrence Score result provides additional insight into the likelihood of colon cancer recurrence that goes beyond existing measures such as nodal assessment, bowel perforation, bowel obstruction, tumor grade, lymphatic or venous invasion, T-Stage and Mismatch Repair (MMR) Status. Not one of these prognostic factors singularly helps identify the majority of patients at risk for recurrence and reduced survival in colon cancer. Current guidelines recommend that patients with any of these clinical and pathologic risk features be considered high risk, with all other patients classified as standard risk. Lymph node involvement, T-stage, and MMR status have proven to be clear prognostic factors, yet apply to a minority of Stage II colon cancer patients.
High Tumor Grade is Not a Marker of Higher Recurrence Risk in Stage II Colon Cancer
Conventional Wisdom of Tumor Grade Does Not Apply in Stage II Colon Cancer
Today, the availability of multiple large studies in this population permits an evidence-based approach in assessing the value of tumor grade in recurrence risk assessment in Stage II colon cancer. Although high tumor grade may be associated with higher risk in advanced stage colon cancer (e.g. Stage III), the relationship of grade to recurrence in Stage II colon cancer is clearly different. The premise that high tumor grade is a poor prognostic factor is largely derived from older studies pooling patients across stages (Stage I-IV) of colon and rectal cancer, which did not allow for the possibility that tumor grade could have different prognostic value by stage or by location (colon vs. rectum).
Consistent Findings in Nearly 3,000 Stage II Colon Cancer Patients Across 5 Large Studies
Grade and QUASAR
In this multivariable analysis from the QUASAR validation study, Colon Recurrence Score result, MMR, and T-stage were the strongest predictors of recurrence risk. High tumor grade was not associated with higher recurrence risk. In fact, in this study, high tumor grade was associated with lower recurrence risk, even accounting for the known association with MMR status.
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