Prognostic factors in gallbladder cancer: a comprehensive systematic review and meta-analysis

Background: Gallbladder cancer (GBC) is one of the most common biliary cancers and is characterized by its high malignancy. Moreover, the incidence of GBC has been increasing over the decades, partly due to advancements in diagnostic techniques and devices. The purpose of this systematic review is to provide a comprehensive assessment of factors influencing the prognosis of GBC. We aim to identify and evaluate both established and controversial prognostic factors, including lymphocyte-monocyte ratio (LMR), adjuvant therapy, carbohydrate antigen 19-9 (CA199), carcinoembryonic antigen (CEA), tumor mutation status, surgical margins, the presence of gallstones, and jaundice. Methods: We conducted a systematic search of eligible studies in PubMed, Cochrane Library, and Embase. Our analysis focused on data from GBC patients who had undergone surgical resection, with the primary outcome being overall survival. Forest plots were generated using hazard ratios (HRs) to visualize the effect sizes, and the Quality in Prognostic Factor Studies (QUIPS) tool was employed to assess the risk of bias. Results: This study synthesized data from 52 studies, encompassing a total of 23,174 patients over the period of 2000 to 2022. Notably, several factors significantly influenced the outcomes of GBC, including LMR (HR =2.17), CEA (HR =1.81), CA199 (HR =1.56), lymph node stage (HR =2.03), T stage (HR =2.37), presence of invasion (HR =1.74), tumor location (HR =1.42), and surgical margins (HR =2.66). Additionally, chemotherapy (HR =0.75) and radiotherapy (HR =0.56) demonstrated marked improvements in overall survival compared to control arms. Jaundice and the presence of gallstones were not defined as independent predictors, as they reflect advanced stage symptoms in GBC. Conclusions: The findings from this comprehensive review offer valuable insights into the assessment of the necessity for aggressive treatment approaches and the prognostication of GBC patients. Furthermore, there is a need for well-designed, ongoing studies to further advance our understanding of this challenging malignancy.