The Role of KRAS Status Among Patients Undergoing Staged Versus Simultaneous Resection for Synchronous Colorectal Liver Metastases

Background: This study aimed to evaluate the impact of surgical timing-simultaneous versus staged resection-on outcomes of patients with colorectal liver metastases (CRLM) in relation to KRAS mutation status, which is a key factor affecting prognosis. Methods: Patients who underwent curative-intent resection for synchronous CRLM (sCRLM) were identified from an international, multi-institutional database. The association between clinicopathologic factors, staged versus simultaneous approach and wild-type (wtKRAS) versus mutated (mtKRAS) KRAS with long-term outcomes was assessed. Results: Among 385 patients who underwent curative-intent resection for sCRLM, 205 (53.2%) individuals underwent a simultaneous primary tumor and CRLM resection; 180 (46.8%) individuals underwent a staged surgical approach. On multivariable analysis, the staged approach remained associated with improved OS compared with the simultaneous approach among patients who had mtKRAS CRLM (HR: 0.62, 95% CI: 0.39-0.99). Patients with mtKRAS and high TBS demonstrated an improved 5-year OS (67.0%, 95% CI: 54.2%-83.0% vs. 47.5%, 95% CI: 31.4%, 71.9%; p = 0.04) compared with a simultaneous procedure. There was no difference in OS among patients with either wtKRAS or mtKRAS and low TBS who underwent staged versus simultaneous resection (p > 0.05). Conclusion: Patients with sCRLM and an aggressive tumor biology as defined by KRAS status and TBS may benefit from a two-stage resection which may improve patient selection relative to achieving better long-term outcomes.