Inability to control metastatic disease -stage iv colon cancer is lethal because metastatic disease destroys vital organs that it metastasizes to (lung, liver, brain, etc) and because chemotherapy and radiation therapy can seldom cure non-resectable disease. the primary tumor is almost always resectable, or it can be by-passed to prevent colonic obstruction, and seldom kills the patient at the site of origin. the tumors generally have inherent resistance to chemotherapy and radiation at their primary site during early stage disease, it is just that low stage tumors are more often cured by surgery, hence their better prognosis. microsatellite instability, if does arise in these cancers, arises early in tumor progression, hence will be present in early stage disease and is not generally acquired in late stage disease.
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