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Improving clinical management of colon cancer through CONNECTION, a nation-wide Colon Cancer Registry and Stratification effort.

Colorectal cancer is still a devastating disease with over 600.000 deaths per year worldwide. This is in part due to poor survival of patients with late stage disease where curative treatment options are limited, but even at stage II around 20% of the patients will develop a recurrence despite effective surgical resection of the primary tumor. Identification of these stage II patients at risk and optimization of the therapy provided is therefore an important goal to improve outcome in colon cancer.

For patients with stage III disease the treatment routinely includes adjuvant chemotherapy, but here estimates are that around 50% of these patients are over-treated as they would have been cured by resection alone. Therefore identification of the patients at risk at this stage of disease is important as it may spare patients the unwanted side effects of chemotherapy.

Recently, distinct biological subgroups are identified in colon cancer using gene expression profiling. Common biological features are identified and a consensus classification revealed four independent subgroups. One is defined by mesenchymal features and has a high recurrence risk and dismal prognosis. The analysis of subgroups allows us to separate patients into high and low risk for recurrences and therefore may provide a new handle for the clinical management of colon cancer patients.

The aim of this study is to use the biological differences that exist in colon cancer subgroups to guide clinical decisions on the use and type of adjuvant therapy, thereby improving the outcome as well as the therapy burden for patients. To achieve this genetic, proteomic and histopathological assays will be developed and validated that depend on the biological differences in the distinct colon cancer subgroups, focusing specifically on the mesenchymal poor-prognosis subgroup. These assays should serve to stratify patients both for the need to obtain adjuvant therapy and the type of therapy.

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