KRAS Mutation Status Predicts Site-Specific Recurrence and Survival After Resection of Colorectal Liver Metastases Irrespective of Location of the Primary Lesion

Ann Surg Oncol. 2016 Jun;23(6):1890-6. doi: 10.1245/s10434-016-5087-5. Epub 2016 Jan 19.

Abstract

Background: The KRAS mutation status is reportedly correlated with poor survival outcome in patients with colorectal liver metastases (CLM); however, its true prognostic impact and the reason for the poor prognosis remain unclear.

Methods: Data on 163 patients with a known KRAS mutation status who underwent curative resection for CLM were retrospectively reviewed. The long-term survival and site-specific incidence of recurrence were then compared between patients with a KRAS mutation (mtKRAS) and those without a mutation (wtKRAS).

Results: The mtKRAS group had a poorer 3-year disease-specific survival (DSS) rate (59.8 vs. 83.6 %, p = 0.016), 3-year recurrence-free survival (RFS) rate (0 vs. 20.2 %, p = 0.069), and median time to surgical failure (TSF) [18.8 vs. 39.7 months, p = 0.001] than the wtKRAS group. The cumulative incidences of liver recurrence and lung recurrence at 3 years were also higher in the mtKRAS group (76.2 vs. 54.7 %, p = 0.060; and 71.9 vs. 37.3 %, p < 0.001, respectively). A multivariate analysis confirmed that an mtKRAS status had a significant effect on the DSS rate (hazard ratio [HR] 2.9, p = 0.006), RFS (HR 2.0, p = 0.004), TSF (HR 2.4, p < 0.001), liver recurrence (HR 1.7, p < 0.001), and lung recurrence (HR 2.6, p < 0.001). Lung-related unresectable recurrences were more frequent (41 vs. 18 %, p = 0.048) and were associated with an earlier TSF (9.6 vs. 14.0 months, p = 0.14) in the mtKRAS group, regardless of the location of the primary lesions.

Conclusions: mtKRAS is associated with poor survival outcome after CLM resection because of a relatively high incidence of lung recurrence and a relatively short TSF.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / mortality*
  • Colorectal Neoplasms / pathology
  • Colorectal Neoplasms / surgery
  • Female
  • Follow-Up Studies
  • Hepatectomy / mortality*
  • Humans
  • Liver Neoplasms / genetics
  • Liver Neoplasms / mortality*
  • Liver Neoplasms / secondary
  • Liver Neoplasms / surgery
  • Male
  • Middle Aged
  • Mutation*
  • Neoplasm Recurrence, Local / genetics
  • Neoplasm Recurrence, Local / mortality*
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Recurrence, Local / surgery
  • Prognosis
  • Proto-Oncogene Proteins p21(ras) / genetics*
  • Retrospective Studies
  • Survival Rate

Substances

  • KRAS protein, human
  • Proto-Oncogene Proteins p21(ras)