Risk Factors for Overall and Disease Free Survival in Those Patients with Multiple Colorectal Liver Metastases in the Era of Target Therapy

Purpose: Although,the number of colorectal liver metastases (CRLM) is decreasingly considered as contraindication to surgery, most of the scores still include the number of lesions (GAME score, Tumor Burden Score) as one of main predictors of worst overall survival.This study aimed to evaluate the outcome after liver surgery of those patients with 5 or more lesions and to identify prognostic factors for survival in such group of patients. Methods: The study population consisted of an european unicentre cohort of patients with CRLM operated from January 2010 to December 2019 and whose data were prospectively collected in the LivermetSurvey registry after Ethics Committee aproval. An univariate and multivariate analyses was performed to identify the risk factors associated with overall and disease free survival in those patients with ≥5 lesions at diagnoses. Results: We included 250 patients of whom 54 patients had ≥5 lesions.The main characteristics of this group: right side primary tumor in 22%, stage N positive of primary tumor in 65%, CEA level at diagnoses in 16.8ng/mL (0.5-2,933), synchronous disease in 78%, KRAS and BRAF mutation 43% and 4%, GAME Score≥4 in 22% and preoperative chemotherapy 91% of whom targeted therapy was administered in 50% of the patients. The median overall survival (OS) and disease free survival (DFS) in this group was 25 months (4-108) and 10 months (0-103) respectively. Multivariate analyses showed that the primary tumor stage N positive (HR=3.41) and right side primary tumor (HR= 1.93) emerged as the strongest risk factor for OS. Regarding DFS, R1 resection (HR=3.09), right side primary tumor (HR=1.88) and KRAS mutation (HR= 1.56) were the main risk factors. The model demonstrated that a median of 30 months of OS could be achieved in selected cases and more than 16 months of DSF was possible providing R0 resection associated with at least an more additional favorable factor. Conclusions: Multiple CRLM is an important factor with impact in long-term survival however longer OS and DFS could be achieved in selected cases.