KRAS Mutation Status Dictates Optimal Surgical Margin Width in Patients Undergoing Resection of Colorectal Liver Metastases

Ann Surg Oncol. 2017 Jan;24(1):264-271. doi: 10.1245/s10434-016-5609-1. Epub 2016 Sep 30.

Abstract

Background: The optimal tumor-free margin width remains controversial and may be inappropriate to investigate without considering differences in the underlying tumor biology.

Methods: R1 resection was defined as margin clearance less than 1 mm. R0 resection was further divided into 3 groups: 1-4, 5-9, and ≥10 mm. The impact of margin width on overall survival (OS) relative to KRAS status [wild type (wtKRAS) vs. mutated (mutKRAS)] was assessed.

Results: A total of 411 patients met inclusion criteria. Median patient age was 58 years (interquartile range, 49.7-66.7); most patients were male (n = 250; 60.8 %). With a median follow-up of 28.3 months, median and 5-year OS were 69.8 months and 55.1 %. Among patients with wtKRAS tumors, although margin clearance of 1-4 mm or more was associated with improved OS compared to R1 (all P < 0.05), no difference in OS was observed when comparing margin clearance of 1-4 mm to the 5-9 mm and the ≥10 mm groups (all P > 0.05). In contrast, among patients with mutKRAS tumors, all three groups of margin clearance (1-4, 5-9, and ≥10 mm) fared no better in terms of 5-year survival compared to R1 resection (all P > 0.05).

Conclusions: While a 1-4 mm margin clearance in patients with wtKRAS tumors was associated with improved survival, wider resection width did not confer an additional survival benefit. In contrast, margin status-including a 1 cm margin-did not improve survival among patients with mutKRAS tumors.

MeSH terms

  • Aged
  • Colorectal Neoplasms / pathology*
  • Female
  • Hepatectomy
  • Humans
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / secondary*
  • Liver Neoplasms / surgery*
  • Male
  • Margins of Excision
  • Middle Aged
  • Mutation
  • Prognosis
  • Proto-Oncogene Proteins p21(ras) / genetics*
  • Survival Rate

Substances

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