KRAS and BRAF Mutations as survival prognostic factors for Metastatic Colorectal Cancer patients after Lung metastasectomy: A Systematic Review and Meta-Analysis

Introduction While knowledge has grown extensively regarding the impact of mutations on colorectal cancer prognosis, their role in outcomes after pulmonary metastasectomy (PM) remains minimally understood. Therefore, in this paper, we conduct a systematic review and meta-analysis of retrospective and prospective studies to evaluate whether KRAS or BRAF mutation status can be independent predictors in colorectal cancer patients undergoing complete lung metastasis surgery.Methods A systematic literature review was performed to identify articles reporting overall survival (OS) of patients who underwent lung metastasectomy for colorectal cancer lung metastases (CRLM), stratified according to KRAS and BRAF mutational status. Hazard ratios (HRs) from multivariate analyses were pooled in the meta-analysis.Results 9 studies, including 1833 patients, were eligible for the meta-analysis. Based on the random effect model, the total frequency of KRAS mutations in 1305 patients who had undergone the lung metastasectomy was 45% and the total 5-year OS in these patients was 55.7%. five of them reported OS stratified according to KRAS mutation. The pooled analysis revealed that KRAS mutation was negatively associated with OS (HR, 1.674; 95% confidence interval [CI], 1.341-2.089; P < .001). the rate of KRAS mutations were lower in the studies with higher male to female ratio. There was statistically significant linear trend in univariate meta-regression to explain effect size variation by male to female ratio of study with coefficient = 0.47 (95% CI 0.03, 0.91), P = 0.03. disease free survival (DFS), thoracic metastases and origin of primary tumor were significantly influenced by KRAS mutation status.Conclusions Our meta-analysis confirms the KRAS mutation as a strong and predictive biomarker which makes overall survival lower in patients with colorectal cancer undergoing pulmonary metastasis surgery. Certainly, this interesting evidence represents the first step towards a deeper understanding of the molecular mechanisms underlying tumor behavior and patient outcomes in a subgroup of clinically selected colorectal cancer patients. By considering tumor molecular characteristics and other clinical-pathological factors, our results confirm the use of new therapeutic models to predict outcomes of patients undergoing colorectal lung metastasis surgery and to isolate both systemic and loco-regional treatment strategies.