BRAF Mutations, Survival, and Recurrence in Patients Undergoing Surgery for Colorectal Cancer Liver Metastases


Key Points

  • BRAF V600E but not non-V600E mutations were associated with significantly poorer outcomes.
  • The BRAF V600E mutation had a stronger association with overall and disease-free survival than did KRAS mutation. 

In a study reported in JAMA Surgery, Margonis et al found that presence of a BRAF V600E mutation was associated with higher risk of recurrence and poorer overall survival among patients undergoing surgical resection of liver metastases from colorectal cancer.

Study Details

The cohort study included 849 evaluable patients (60% male) who underwent hepatectomy for colorectal cancer liver metastases with curative intent from January 2000 through December 2016 at institutions participating in the International Genetic Consortium for Colorectal Liver Metastasis and who had available data on BRAF and KRAS mutation status. Among all patients, 5.1% had a mutated (mut) BRAF/wild-type (wt) KRAS (V600E and non-V600E) genotype; 56.5% a wtBRAF/wtKRAS genotype; and 38.4% a wtBRAF/mutKRAS genotype. Compared with the wtBRAF/wtKRAS group, patients with mutBRAF/wtKRAS were more likely to be female (62.8% vs 35.2%), aged ≥ 65 years (51.2% vs 36.9%), have right-sided primary tumors (62.8% vs 17.4%), and present with metachronous liver metastasis (64.3% vs 46.8%).

Prognostic Associations

On multivariate analysis, presence of V600E (hazard ratio [HR] = 2.76, P < .001) but not non-V600E BRAF mutation (HR = 1.75, P = .35) was associated with significantly poorer overall survival. Similarly, presence of V600E (HR = 2.04, P = .002) but not non-V600E mutation (HR = 0.67, P = .48) was associated with significantly poorer disease-free survival. Compared with KRAS mutation, the V600E BRAF mutation, which was the strongest overall prognostic factor for both overall and disease-free survival, had a stronger association with overall survival (β coefficient = 10.15 vs 2.94) and disease-free survival (β coefficient = 7.14 vs 2.27). 

The investigators concluded, “The presence of the V600E BRAF mutation was associated with worse prognosis and increased risk of recurrence. The V600E mutation was not only a stronger prognostic factor than KRAS but also was the strongest prognostic determinant in the overall cohort.”

The study was supported by the Bodossaki Foundation, Drs. Keith and Valda Kaye Research Fund, and Carolyn Pastorini Research Fund.

Matthew J. Weiss, MD, of the Department of Surgery, Johns Hopkins University School of Medicine, is the corresponding author for the JAMA Surgery article.

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