Prognostic factors for resected cases with gallbladder carcinoma: A systematic review and meta-analysis

Abstract

Objective: Current meta-analysis was performed to systematically evaluate the potential prognostic factors for overall survival (OS) among resected cases with gallbladder carcinoma (GBC). Methods: PubMed, EMBASE, and the Cochrane Library were systematically retrieved and hazard ratio (HR) and its 95% confidence interval (CI) were directly extracted from the original study or roughly estimated via Tierney’s method. Standard Parmar modifications were used to determine pooled HRs. Results: A total of 36 studies with 11502 cases were identified. Pooled results of univariate analyses indicated that advanced age (HR=1.02, P=0.00020), concurrent gallstone disease (HR=1.22, P=0.00200), elevated preoperative CA199 level (HR=1.93, P<0.00001), advanced T stage (HR=3.09, P<0.00001), lymph node metastasis (HR=2.78, P<0.00001), peri-neural invasion (HR=2.20, P<0.00001), lymph-vascular invasion (HR=2.37, P<0.00001), vascular invasion (HR=2.28, P<0.00001), poorly differentiated tumor (HR=3.22, P<0.00001), hepatic side tumor (HR=1.85, P<0.00001), proximal tumor (neck/cystic duct) (HR=1.78, P<0.00001), combined bile duct resection (HR=1.45, P<0.00001), and positive surgical margin (HR=2.90, P<0.00001) were well-established prognostic factors. Pathological subtypes (P=0.53000) and postoperative adjuvant chemotherapy (P=0.70000) were not prognostic factors. Pooled results of multi-variate analyses indicated that age, gallstone disease, preoperative CA199, T stage, lymph node metastasis, peri-neural invasion, lymph-vascular invasion, tumor differentiation status, tumor location (peritoneal side vs hepatic side), surgical margin, combined bile duct resection, and postoperative adjuvant chemotherapy were independent prognostic factors. Conclusion: Various prognostic factors have been identified beyond the 8th AJCC staging system. By incorporating these factors into a prognostic model, a more individualized prognostication and treatment regime would be developed. Upcoming multinational studies are required for the further refine and validation.