Anticipating the clinical use of prognostic gene expression-based tests for colon cancer stage II and III: is Godot finally arriving?

PURPOSE According to current recommendations for adjuvant treatment, patients with colon cancer stage II are not routinely offered chemotherapy, unless considered to have a high risk of relapse based on specific clinicopathological parameters. Following these criteria, it is challenging to identify the subgroup of patients that will benefit the most from adjuvant treatment. Contrarily, patients with colon cancer stage III are routinely offered chemotherapy, but due to expected adverse effects and frailty, elderly patients are often excluded from standard protocols. Colon cancer is a disease of the elderly and accordingly, there is a large subgroup of patients for which guidelines for adjuvant treatment remain less clear. In these two clinical settings, improved risk stratification has great potential impact on patient care, anticipating that high-risk patients will benefit from chemotherapy. However, microsatellite instability is the only molecular prognostic marker recommended for clinical use. EXPERIMENTAL DESIGN In this perspective, we provide an updated view on the status and clinical potential of the many proposed prognostic gene expression-based tests for colon cancer stage II and III. RESULTS The main limitation for clinical implementation is lack of prospective validation. For patients with stage II, highly promising tests have been identified and clinical trials are ongoing. For elderly patients with stage III, the value of such tests has received less focus, but promising early results have been shown. CONCLUSION Although awaiting results from prospective trials, improved risk assessment for patients with stage II and III is likely to be achieved in the foreseeable future.