Are Gene Signatures Ready for Use in the Selection of Patients for Adjuvant Treatment?

Fluoropyrimidine-based chemotherapy improves survival in stage III colon cancer patients in the adjuvant setting, whereas its clinical benefit in stage II is limited. Adjuvant therapy could be considered in patients with high-risk stage II disease, who are more likely to benefit from chemotherapy. Clinicopathological factors have been routinely used for risk stratification in stage II, as well as microsatellite instability (MSI) analysis, which has been recently incorporated in clinical guidelines as a prognostic marker. Other molecular markers, such as KRAS and BRAF mutations, suggested improving accuracy in prognostic classification in non-metastatic disease. Recent data derived from randomized clinical trial demonstrated that KRAS/BRAF gene mutations are associated with worse outcome depending on MSI status and tumor localization. Similarly, supervised gene expression signatures have refined recurrence risk stratification in several prospective studies although the clinical utility is still debatable. In this review, we focus on the new data on molecular and gene expression profiling in non metastatic colon cancer and the impact on prognostication and treatment decision.