RAS Mutation is Associated with Unsalvageable Recurrence Following Hepatectomy for Colorectal Cancer Liver Metastases

Background: RAS mutation status predicts survival after hepatectomy for colorectal liver metastases (CRLM) and survival after repeat hepatectomy for intrahepatic recurrence. This study was aimed at determining the impact of RAS mutation on amenability of recurrence to local therapy and on post-recurrence survival following hepatectomy. Methods: CRLM patients with recurrence at any location after curative intent hepatectomy during the period 2006–2015 were retrospectively analyzed. Factors associated with recurrence not amenable to local therapy and with post-recurrence survival were evaluated. Results: Of 566 patients with recurrence, 309 (54.6%) underwent chemotherapy only, 189 (33.4%) underwent surgical resection, 47 (8.3%) underwent ablation, and 21 (3.7%) underwent radiation therapy. Median post-recurrence survival was significantly longer in patients with local therapy than in those with chemotherapy only (65.1 vs. 26.5 months, p < 0.0001). RAS mutation (p = 0.01), presence of extrahepatic metastases (p = 0.0006), and positive surgical margin at prior hepatectomy (p = 0.01) were associated with recurrence not amenable to local therapy. RAS mutation [hazard ratio (HR) 1.49, p = 0.0012], disease-free interval < 12 months (HR 1.76, p < 0.0001), recurrence at multiple organs (HR 1.71, p < 0.0001), and recurrence not amenable to local therapy (HR 4.11, p < 0.0001) were independent risk factors for shorter post-recurrence survival. RAS mutation was associated with poor post-recurrence survival in both patients who received local therapy and those who received chemotherapy only. Conclusions: RAS mutation predicts recurrence not amenable to any local therapy and shorter post-recurrence survival after hepatectomy for CRLM.