Abstract
Locally advanced and borderline resectable gallbladder cancer (LA/BR-GBC) has poor outcomes with primary surgery alone, and neoadjuvant chemotherapy (NACT), with or without consolidation chemoradiation, is increasingly used in high-volume hepatobiliary practice. PubMed, Scopus, Web of Science, Cochrane CENTRAL, the International Clinical Trials Registry Platform and ClinicalTrials.gov were searched from 1 January 2010 to 15 May 2026 for studies of adults with cT3/cT4, node-positive, vascular-involved or adjacent-organ-involved gallbladder cancer without distant metastases, treated with platinum-gemcitabine-based neoadjuvant therapy with or without consolidation radiation. Proportions were pooled using a DerSimonian-Laird random-effects model on the Freeman-Tukey double-arcsine scale. Egger testing, leave-one-out sensitivity analysis, subgroup analysis and GRADE certainty assessment were performed. Fifteen studies including 2094 patients were included, and eleven contributed to quantitative synthesis. The pooled radiologic objective response rate was 62.5% (95% CI 53.1-71.5%), the pooled intention-to-treat resection rate was 44.0% (95% CI 33.9-54.3%), and the pooled R0 rate among resected patients was 89.0% (95% CI 80.7-95.2%). The POLCAGB phase III trial reported improved median overall survival with neoadjuvant chemoradiation compared with NACT alone (21.8 versus 10.0 months) and a higher R0 rate (51.6% versus 29.7%; p = 0.01). The available evidence supports NACT as a rational first step in appropriately selected LA/BR-GBC, with selective consolidation chemoradiation and disciplined surgical selection. Multicentre response-adapted randomized trials are still required to define the optimal neoadjuvant regimen and sequencing strategy.
Keywords: Gallbladder Cancer, Meta-analysis, Neoadjuvant Chemoradiation, Neoadjuvant Chemotherapy, PRISMA 2020, R0 Resection.