Since the last ASCO meeting in June 2008 not only has KRAS made headlines but also microsatellite instability (MSI).
Microsatellite instability has developed into the most important prognostic and predictive marker for patients with stage II colon cancer. Recent studies presented by Dr. Daniel Sargent at ASCO showed that patients with stage II colon cancer who have microsatellite instability did not benefit from 5-FU chemotherapy. Therefore these patients with no risk factors such as clinical obstruction, lymphovascular invasion, poorly differentiated adenocarcinoma, or insufficient lymph node collection should not receive 5-FU.
Since this data emerged we have evaluated every patients with stage II colon cancer for MSI to make a better treatment plan. MSI findings do not impact stage III disease (meaning positive lymph node involvement).
In the future it will be more and more important to understand colon cancer better, including how it behaves despite looking the same under the microscope. We don’t yet understand why MSI is associated with better outcomes, but colon cancers with MSI do not benefit from 5-FU chemotherapy.
There is, in fact a prospective clinical trial, ongoing called E-5202 which enrolls patients with stage II colon cancer who will be tested for MSI and 18q deletion. Patients with loss of 18q or microsatelite stable tumor will be randomly treated with FOLFOX with or without Avastin. Patients with tumors who did not lose 18q and have MSI will be only observed. This is an important trial to demonstrate if these clinical markers are helpful in treatment decisions.
Please make sure that you discuss these molecular markers when you have stage II colon cancer.