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

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.