Expert Discusses Tumor Location and Mutational Status in CRC

Angelica Welch
Published: Thursday, Jun 29, 2017

Julien Taieb, MD

Julien Taieb, MD

Right-sided tumors in colon cancer have been associated with poorer outcomes than left-sided tumors.

In a study presented at this year’s World Congress on Gastrointestinal Cancer, investigators aimed to evaluate the prognostic value of primary tumor location in patients with fully resected colon cancer, as well as its relationship to microsatellite instability-high (MSI-H), RAS, and BRAF mutational status.

Of 40% of patients who had a right-sided tumor, 10% were MSI-H, 50% were RAS-mutant, and 11% were BRAF-mutant. Right-sided tumors were associated with a shorter overall survival (OS) (HR, 1.25; CI, 1.02 - 1.54, P = .03). Similar results were demonstrated for MSI-H and microsatellite stable (MSS) patients.

In an interview with OncLive during the congress, lead author Julien Taieb, MD, head of the gastroenterology and GI oncology department of the Georges Pompidou European Hospital, Paris Descartes University, discussed the prognostic value of primary tumor location in colon cancer.

OncLive: Could you provide an overview of this study?

Taieb: For the past year and a half, there has been a big buzz around sidedness of primary tumor location in colon cancer patients in the metastatic setting. First because it seems like a good prognostic marker—if you have a right-sided tumor you have a poor prognosis as compared to a left-sided tumor. And second, it has been shown by the German study FIRE-3/AIO first and then confirmed in the United States, that left colon cancer will maybe respond well to anti-EGFR therapies and maybe right colon cancers respond better to anti-VEGF therapies. So, it is also a kind of predictive marker to choose the best targeted agent in each patient.

Moreover, we are at the time of molecular classification, but of course this classification is not available everywhere in the world. So, by knowing what to do based on right or left colon cancer is a big advantage in developing countries. 

What were the significant findings?

Here, for the first time, we have looked at a clinical trial prospectively performed on more than 2000 patients with stage III colon cancer—so, before the occurrence of metastatic disease. We asked, “Is sidedness predictive, and is sidedness prognostic?” 

We had a trial testing anti-EGFR plus chemotherapy, versus chemotherapy. This trial was negative, as anti-EGFR did not improve survival. This trial has been used with assessments for all mutations status like BRAF, RAS, with NRAS and KRAS, MSI status—it characterizes each tumor.

Then, we moved to sidedness, and what we found was that disease-free survival (DFS) with no recurrence is not impacted by the sidedness. But, if you relapse, the survival after relapse is clearly impacted by the sidedness, and the right-sided tumors—as previously described—have poor prognosis.

When looking at sidedness and the effect of anti-EGFR in RAS wild-type patients, what we have seen is that you have a positive effect of cetuximab in this purified patient—which is not significant but better than chemotherapy alone—and this is true in right and left, so there is no predictive value either.

But, surprisingly, as the patients were very well characterized, we looked in different molecular groups of what is happening on recurrence by sidedness. The first point is that MSI/MSS is exactly the same, no influence of sidedness on DFS. But, if you look at BRAF and KRAS mutant, it seems like having this mutant population, having a right-sided tumor is a good prognostic factor—which is very surprising and has never been described before.

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