Neoadjuvant Chemotherapy in Locally Advanced and Borderline Resectable Gallbladder Cancer: A PRISMA 2020 Systematic Review and Meta-analysis of Radiologic Response, Resection, R0 Status, and Survival

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 (ICTRP), and ClinicalTrials.gov were searched from 1 January 2010 to 15 May 2026 for studies involving adults with cT3/cT4, node-positive, vascular-involved, or adjacent-organ-involved gallbladder cancer without distant metastases who were 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 2,094 patients were included, and eleven contributed to the 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 resection 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 vs. 10.0 months) and a higher R0 resection rate (51.6% vs. 29.7%; p = 0.01). The available evidence supports NACT as a rational first step in appropriately selected patients with LA/BR-GBC, with selective consolidation chemoradiation and disciplined surgical selection. However, multicentre, response-adapted randomized trials are still required to define the optimal neoadjuvant regimen and sequencing strategy.