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Critical appraisal of surgical margins according to KRAS status in liver resection for colorectal liver metastases: should surgical strategy be influenced by tumor biology?

Abstract: Background: KRAS mutation is a negative prognostic factor for colorectal liver metastases. Several studies have investigated the resection margins according to KRAS status, with conflicting results. The aim of the study was to assess the oncologic outcomes of R0 and R1 resections for colorectal liver metastases according to KRAS status. Methods: All patients who underwent resection for colorectal liver metastases between 2010 and 2015 with available KRAS status were enrolled in this multicentric international cohort study. Logistic regression models were used to investigate the outcomes of R0 and R1 colorectal liver metastases resections according to KRAS status: wild type versus mutated. The primary outcomes were overall survival and disease-free survival. Results: The analysis included 593 patients. KRAS mutation was associated with shorter overall survival (40 vs 60 months; P = .0012) and disease-free survival (15 vs 21 months; P = .003). In KRAS-mutated tumors, the resection margin did not influence oncologic outcomes. In multivariable analysis, the only predictor of disease-free survival and overall survival was primary tumor location (P = .03 and P = .03, respectively). In KRAS wild-type tumors, R0 resection was associated with prolonged overall survival (74 vs 45 months, P < .001) and disease-free survival (30 vs 17 months, P < .001). The multivariable model confirmed that R0 resection margin was associated with prolonged overall survival (hazard ratio = 1.43, 95% confidence interval: 1.01?2.03) and disease-free survival (hazard ratio = 1.42; 95% confidence interval: 1.06?1.91). Conclusions: KRAS-mutated colorectal liver metastases showed more aggressive tumor biology with inferior overall survival and disease-free survival after liver resection. Although R0 resection was not associated with improved oncologic outcomes in the KRAS-mutated tumors group, it seems to be of paramount importance for achieving prolonged long-term survival in KRAS wild-type tumors.

 Fuente: Surgery, 2024, 176, 124-133

 Publisher: Elsevier

 Year of publication: 2024

 No. of pages: 10

 Publication type: Article

 DOI: 10.1016/j.surg.2024.02.008

 ISSN: 0039-6060,1532-7361

 Publication Url: https://doi.org/10.1016/j.surg.2024.02.008

Authorship

RHAIEM, RAMI

DURAMÉ, ADRIEN

PRIMAVESI, FLORIAN

DORCARATTO, DIMITRI

SYN, NICHOLAS

HOZ RODRÍGUEZ, ÁNGELA DE LA

DUPRÉ, AURÉLIEN

PIARDI, TULLIO

BLANCO FERNÁNDEZ, GERARDO

PRADA VILLAVERDE, ARANCHA

ROBERTO FERNANDEZ SANTIAGO

FERNÁNDEZ-MORENO, MARÍA-CARMEN

FERRET, GEORGINA

LÓPEZ BEN, SANTIAGO

SUÁREZ MUÑOZ, MIGUEL Á.

PÉREZ-ALONSO, ALEJANDRO

KOH, YE-XIN

JONES, ROBERT

MARTÍN-PÉREZ, ELENA