Surgical Resection for Recurrence After Two-Stage Hepatectomy for Colorectal Liver Metastases Is Feasible, Is Safe, and Improves Survival

Background: Recurrence rates are high for patients who have undergone two-stage hepatectomy (TSH) for bilateral colorectal liver metastases, and there is no established treatment approach for recurrent disease. This study aimed to determine the feasibility, safety, and prognostic impact of surgical resection for recurrence after TSH and the prognostic role of RAS mutation in this cohort. Methods: The study included 137 patients intended to undergo TSH for bilateral colorectal metastases during 2003–2016. Clinicopathologic factors were compared using univariate and multivariate analyses. Results: One hundred eleven patients (81%) completed TSH. The median recurrence-free survival in these patients was 12 months. Of the 83 patients with subsequent recurrence, 31 (37%) underwent resection for recurrence, and 11 underwent multiple resections for recurrence. Forty-eight operations were performed for recurrence: 23 repeat hepatectomies, 14 pulmonary resections, 5 locoregional resections, and 6 concurrent resections in multiple organ sites. The median overall survival (OS) among patients with recurrence was 143 months for patients who underwent resection and 49 months for those who did not (P < 0.001). On multivariate analysis, resection for recurrence (hazard ratio [HR] 0.25; 95% CI 0.10–0.54, P < 0.001) was associated with better OS, whereas RAS mutation (HR 2.25; 95% CI 1.16–4.50, P = 0.016) and first recurrence in multiple sites (HR 2.28; 95% CI 1.17–4.37, P = 0.016) were independent predictors of worse overall survival. Conclusions: In patients who have undergone TSH for bilateral colorectal liver metastases, recurrence is frequent and should be treated with resection whenever possible. Patients with wild-type RAS fare particularly well with resection for recurrence.