COMMENTARY

Recurrent Colon Cancer: All About Location, Location, Location

David J. Kerr, CBE, MD, DSc, FRCP, FMedSci

Disclosures

February 27, 2017

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Hello. I am David Kerr, professor of cancer medicine at the University of Oxford.

Some of you may remember that during the summer, Alan Venook and I had a  fascinating conversation about his big presentation at the American Society of Clinical Oncology (ASCO) meeting, in which he looked at the prognostic sidedness of colorectal cancer in terms of some of the advanced disease trials that he and his team had been running. In brief, he showed that there seemed to be a prognostic difference according to which side the tumor originated from. Left-sided tumors tended to do better than right-sided tumors. This is all in advanced disease. It was a very interesting observation that gathered a lot of interest at the meeting, and Alan explained it very well in our earlier video together.

I thought that we should follow this up. I would like to report on a small study[1] of our own that appeared recently in Annals of Oncology. As you know, we at Oxford University have a big interest in adjuvant chemotherapy for colorectal cancer. We took a couple of thousand patients whom we had analyzed carefully from our VICTOR[2] and QUASAR 2[3] adjuvant trials. This allowed us to do multivariate modeling in which we looked at conventional demographic factors, such as stage, and molecular markers that we had previously genotyped, such as KRAS, BRAF, p53, chromosomal instability, PIK3CA mutations—things that we have been interested in for some time.

We put this all into the model to look at overall survival, relapse-free survival, and time from relapse to death. We showed that there was an overall survival advantage prognostically in favor of left-sided tumors. However, when we looked at time from diagnosis to relapse, there was no difference at all. Sidedness does not have any impact on risk for recurrence from primary colorectal cancer. When we looked at time from relapse to death, again we saw a very large difference in the survival curves where left-sided tumors fared better than right.

When we put it into multivariate modeling, it was independent of BRAF, microsatellite instability, et cetera, in keeping with Alan Venook's findings. On recurrence, right-sided tumors are prognostically worse or phenotypically more aggressive than tumors that originate from the left.

As far as we can tell, the conventional biological markers do not explain this difference, so there are yet-to-be-discovered biomarkers of aggressiveness that separate the right- and left-sided tumors. We know that they derive from different elements of the embryologic gut, but we need to look more carefully, perhaps using next-generation sequencing, to see which markers drive this difference in aggressiveness on relapse. Isn't that interesting?

It's a nice wee study, presented recently in Annals of Oncology. I would be very interested in any comments or questions that you might care to post.

As always, thanks for listening. For the time being, Medscapers ahoy.

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