Risk Factors and Clinical Predictors Associated with Incidental Gallbladder Cancer: A Systematic Review and...

Gallbladder cancer is the fifth most common gastrointestinal cancer worldwide, often diagnosed incidentally after cholecystectomy for presumed benign disease. Previous studies have reported geographic variations in the incidence of incidental gallbladder cancer (IGBC), but comprehensive pooled estimates examining multiple predictors of IGBC are lacking. The study aims to synthesize the risk factors and clinical predictors associated with IGBC in patients undergoing cholecystectomy for benign gallbladder conditions.

This systematic review and meta-analysis assessed studies published between January 2010 and February 2024 in databases from EMBASE, PUBMED-MEDLINE, and Scopus. Eligible studies included observational study designs evaluating risk or predictive factors for IGBC diagnosed during or after cholecystectomy for presumed benign gallbladder disease. Heterogeneity across studies was assessed using the I² statistic. Sensitivity analyses were conducted to explore the robustness of the pooled estimates.

Of 2899 studies screened, 18 were included in the systematic review and 9 of these were included in the meta-analysis, covering 788,214 patients undergoing cholecystectomy. Advancing age (OR:1.09; 95% CI:1.07-1.12, I²=55.9%), female gender (OR:1.91; 95% CI:1.33-2.75, I² = 72.1% ), elevated alkaline phosphatase (OR:1.68; 95% CI:1.41-2.00, I² = 0%), polyp size > 10 mm (OR:8.63; 95% CI:1.95-38.26, I² = 0%), and open cholecystectomy (OR:9.20; 95% CI:5.68-14.89, I² = 83.5%) were found to have association with IGBC. Large gallstones (> 3 cm) showed no significant association. Risk of bias was low, and sensitivity analyses confirmed model robustness.

This review identifies key demographic, and clinical factors associated with IGBC. These findings support the need for risk-based preoperative evaluation and careful intraoperative vigilance, particularly in patients with advanced age, female gender, elevated alkaline phosphatase, and larger gallbladder polyps. Incorporating these predictors into clinical decision-making may guide targeted histopathological examination policies, leading to earlier GBC detection and improved patient outcomes. PROSPERO Registration No: CRD42024528982.