KRAS Might be Prognostic for Colorectal Cancer Liver Metastases Resection

Recurrence-free survival after colorectal cancer liver metastases surgery linked to KRAS status

medwireNews: K-Ras Mutations may predict poor recurrence-free survival (RFS) in patients who undergo liver surgery for colorectal cancer (CRC) metastases, US researchers have found.

Three-year RFS was 46% for the 118 patients with Wild-type K-ras versus 30% for the 51 patients with a K-ras mutation and K-ras status remained a significant risk factor for RFS in multivariate analysis, with a hazard ratio of 1.9.

The team from Memorial Sloan-Kettering Cancer Center in New York also reports that patients with K-ras mutations had significantly higher 3-year cumulative rates of recurrence to sites other than the liver than those without K-ras mutations, at 13.4% versus 2.0% for spread to bone and 58.0% versus 33.2% to the lung. There was also a trend towards an increased rate of brain metastases, at 14.5% versus 2.0%.

“These trends need to be examined in larger cohorts of patients to determine whether this is really accurate and whether changes in follow-up should be implemented for patients with KRAS [mutation]”, write Nancy Kemeny and co-authors in Cancer.

Although 3-year overall survival (OS) was lower in patients with a K-ras mutation than those without, at 81% versus 95%, K-ras status was not a significant predictor in multivariate analysis.

Noting this OS result differs from those of previous studies, the researchers believe that the use of both systemic and hepatic arterial infusion after liver resection in the present study patients may have reduced the risk of recurrent liver metastases and thereby improved OS.

Editorialists Kjetil Søreide, and co-authors, from Stavanger University Hospital in Norway, say that the current results corroborate previous studies, making it tempting to suggest K-ras is a “strong and independent Prognostic factor” that “overrules” clinical risk scores and other prognostic markers for patients undergoing liver surgery for metastases.

However, while the different study cohorts are heterogeneous in size and patient selection, they showed a very low prevalence of the BRAF mutation pointing to a “somewhat preselected population of patients”.

This “questions the role of KRAS as a useful prognostic Biomarker in an upfront selection of patients with [colorectal cancer liver metastases] and the proposed relation to prognosis”, Kjetil Søreide et al write.

“More importantly, it raises doubts regarding the role of KRAS in decision-making prior to surgical resection.”

They conclude: “Whether KRAS is truly a biomarker for cancer biology or a byproduct of patient selection therefore remains an open question.”

Reference

Kemeny N, Chou J, Capanu M, et al. KRAS mutation influences recurrence patterns in patients undergoing hepatic resection of colorectal metastases. Cancer 2014; Early online version, 25 August. DOI: 10.1002/cncr.28954

Søreide K, Sandvik O, Søreide J. KRAS mutation in patients undergoing hepatic resection for colorectal liver metastasis: A biomarker of cancer biology or a byproduct of patient selection? Cancer 2014; Early online version, 25 August. DOI: 10.1002/cncr.28979

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