MSI CONFIRMED AS PROGNOSTIC FACTOR OF STAGE II COLORECTAL CANCER 

Hello. I am David Kerr, Professor of Cancer Medicine at the University of Oxford, and past President of the European Society for Medical Oncology (ESMO). Today I want to talk about cancer risk and how we use molecular markers to better categorize and sub-define that.

An interesting study by Dr. Merok and a group from Oslo University Hospital in Norway was published recently in theAnnals of Oncology.^[1] They looked at a very large consecutive series of roughly 1000 patients with colorectal cancer who underwent resection and pathologic examination in their hospital. They analyzed the microsatellite instability (MSI; indicating DNA damage), of the cancers using a polymerase chain reaction methodology that was well worked out and well described.

They found that around 14% of patients' cancers were MSI. For these patients, MSI appeared to confer a rather better prognosis. Most of these benefits were seen for patients with stage II rather than stage III disease. In those patients [with stage II disease], relapse-free survival at 5 years was around 74% for those who were MSI, vs 56% for those who were microsatellite stable. This is a very significant effect, with a hazard ratio of around 2. These findings were in keeping with other studies to which we at Oxford have contributed and with meta-analytical overviews.

The data are clear and compelling. For those of us who are looking after patients with gastrointestinal cancers, if the patient with stage II colorectal cancer has MSI disease and is mismatch repair deficient, there is no obvious benefit for offering adjuvant chemotherapy. I think we should codify that when the next set of guidelines is written, whether by the American Society of Clinical Oncology, ESMO, or the National Comprehensive Cancer Network; we should include MSI as a new molecular marker for a really good prognosis that therefore defines a group of patients who are unlikely to receive any clinically important benefits from the utilization of adjuvant chemotherapy in that setting.

This was an important confirmatory study. The message is clear. Let's act: Let's codify it and get it into guidelines; let's get the word out on the streets. If you have stage II colorectal cancer that is MSI, the prognosis is so good, and the benefits of adjuvant chemotherapy are so vanishingly small, that I would not recommend it -- and I suggest neither should you.

As always, thank you for listening. I am keen to take any further comments or to discuss any of the points I have made during this brief talk.