Primary tumor location may not predict non-metastatic colon cancer outcomes

Last Updated: 2017-11-30

By David Douglas

NEW YORK (Reuters Health) - In patients with stage 3 colon cancer, primary tumor location (PTL) - according to BRAF and RAS mutations, and microsatellite instability (MSI) status - showed no prognostic value in a post hoc analysis of data from the PETACC-8 study.

In a November 22 online article in JAMA Oncology, Dr. Julien Taieb of Universite Paris Descartes, France, and colleagues note that PTL has been a clear and consistent predictor of overall survival in metastatic colorectal cancer, but not in stage 3 non-metastatic colorectal disease.

To investigate further, the team examined data on 1,869 PETACC-8 participants with available tumor blocks of resected stage 3 colon adenocarcinoma. The patients had been receiving adjuvant treatment with FOLFOX (folinic acid, fluorouracil, and oxaliplatin) with or without cetuximab.

Of these patients, 40% had a right-sided tumor, 10% had MSI, 50% had RAS mutations, and 11% had BRAF mutations.

Although right-sided tumor location was not prognostic for disease-free survival (DFS) overall, it was associated with significantly shorter survival after relapse (hazard ratio, 1.54) and shorter overall survival (HR, 1.25).

DFS was similar between microsatellite-stable tumors and tumors with MSI, better in right-sided than in left-sided tumors among patients with RAS mutations, and worse in right-sided than in left-sided tumors among patients with RAS and BRAF double wild-type mutations.

The researchers point out that no benefit or detriment of adding cetuximab to FOLFOX was found in patients with stage 3 left-sided or right-sided tumors.

However, they note that "the association with disease recurrence appears to vary for patients with stage 3 colon cancer and RAS or BRAF mutations versus those with double wild type."

In an email to Reuters Health, Dr. Taieb further observed, "If sidedness seems a strong prognostic and predictive factor in metastatic patients, it is not the case in non-metastatic disease. And no treatment modification or stratification in clinical trials seems warranted regarding primary tumor location in these patients."

Dr. Frank A. Sinicrope of Rochester, Minnesota, told Reuters Health by email, "Among patients whose colon cancers harbored RAS mutations, better survival occurred if the tumor was located in the right versus left colon, and this was also seen among patients whose cancer recurred."

Dr. Sinicrope, co-leader of the GI cancer program at the Mayo Clinic Comprehensive Cancer Center, added, "The association of the KRAS oncogene and prognosis by primary tumor site are consistent with those previously reported for the same chemotherapy treatments evaluated in the U.S. adjuvant trial NCCTG N0147."

SOURCE: http://bit.ly/2AhkjAV

JAMA Oncol 2017.