Tumor Biology and Surgical Margin Patterns in Colorectal Liver Metastases: Association Between KRAS/BRAF Status and Type of Resection Margin—BRAF-KRAS LiverMet Collaborative Group

BACKGROUND: Surgical strategies for colorectal liver metastases (CRLM) have progressively evolved toward parenchyma-sparing approaches, increasing the relevance of understanding the relationship between tumor biology and resection margin patterns. In parallel, KRAS and BRAF mutations have emerged as key determinants of tumor behavior in CRLM. The interaction between mutational status and surgical margin type, however, remains insufficiently characterized. METHODS: This multicenter retrospective study included patients undergoing curative-intent liver resection for CRLM between 2016 and 2021 across 17 international HPB centers. Clinicopathological variables were compared according to mutational status and margin type. RESULTS: Among 1078 eligible patients, KRAS-mutated patients more frequently presented synchronous metastases, nodal involvement, and administration of perioperative chemotherapy compared with wild-type patients. Higher tumor burden was associated with both R1 parenchymal (R1P) and R1 vascular (R1V) resections. Within KRAS-mutated patients, synchronous disease and bilobar involvement were more frequently associated with R1P resections. CONCLUSIONS: KRAS/BRAF mutational status is associated with distinct clinicopathological patterns in patients undergoing liver resection for CRLM. Higher tumor burden and biologically aggressive disease features are more frequently associated with R1P and R1V resections, particularly among KRAS-mutated tumors.