Prognostic Relevance of Surgical Margins According to KRAS and BRAF Status in Colorectal Liver Metastases: BRAF-KRAS LiverMet Collaborative Group

Background: Hepatic resection combined with systemic therapy represents the standard of care for colorectal liver metastases (CRLMs). Although parenchyma-sparing surgery prioritizes R0 resection and preserves liver function, the clinical relevance of minimal margins remains debated. At the same time, tumor biology, particularly KRAS and BRAF mutations, has emerged as a key determinant of outcomes. This study investigated whether mutational status modifies the impact of resection margin type on survival and recurrence. Methods: This international multicenter study included patients undergoing curative-intent liver resection for CRLMs (2016–2021) across 17 hepatopancreatobiliary centers. Only patients with known KRAS/BRAF status and documented margin type were analyzed. Margins were classified as R0, parenchymal R1 (R1P) or vascular R1 (R1V). Results: Among 1078 patients (592 wild-type, 451 KRAS-mutated, 35 BRAF-mutated), R1P resection was associated with significantly worse overall survival than R0 (53 % vs 61 %; p < 0.0001), with the greatest detriment observed in KRAS-mutated tumors. In contrast, R1V was not significant in all molecular subgroups. Consistently, R1P margins were associated with higher recurrence rates in both wild-type and mutated patients, including KRAS and BRAF subgroups. Conversely, R1V margin was not associated with higher recurrence risk. Conclusions: In CRLMs, the prognostic relevance of surgical margins may depend on tumor biology. For BRAF/KRAS wild-type disease, R0 resection remains the preferred goal, whereas the role of wider margins in high-risk molecular subgroups requires further validation. Preoperative molecular profiling may support more individualized surgical planning.