Efficacy of Neoadjuvant Therapy in Gallbladder Cancer - a meta-analysis utilising reconstructed time-to-event data

Sean Loke; Chen Ee Low; Benedict Ding Chao Ong; Kunlin Xie; Alfred Wei Chieh Kow; Jia-Hao Law

doi:10.1016/j.gassur.2025.102133

Efficacy of Neoadjuvant Therapy in Gallbladder Cancer - a meta-analysis utilising reconstructed time-to-event data

J Gastrointest Surg. 2025 Jun 26:102133. doi: 10.1016/j.gassur.2025.102133. Online ahead of print.

Authors

Sean Loke¹, Chen Ee Low¹, Benedict Ding Chao Ong¹, Kunlin Xie², Alfred Wei Chieh Kow³, Jia-Hao Law⁴

Affiliations

¹ Yong Loo Lin School of Medicine, National University of Singapore, 10 Medical Dr, Singapore 117597, Singapore.
² Liver Transplant Centre, West China Hospital, Sichuan University, 37 Guoxue Lane, Wuhou District, Chengdu, Sichuan, China.
³ Yong Loo Lin School of Medicine, National University of Singapore, 10 Medical Dr, Singapore 117597, Singapore; Division of Hepatobiliary & Pancreatic Surgery, Department of Surgery, National University Hospital, 1E Kent Ridge Road, Singapore 119228, Singapore; National University Centre for Organ Transplantation, National University Hospital, 1E Kent Ridge Road, Singapore 119228, Singapore.
⁴ Division of Hepatobiliary & Pancreatic Surgery, Department of Surgery, National University Hospital, 1E Kent Ridge Road, Singapore 119228, Singapore; National University Centre for Organ Transplantation, National University Hospital, 1E Kent Ridge Road, Singapore 119228, Singapore. Electronic address: jia_hao_law@nuhs.edu.sg.

PMID: 40581320
DOI: 10.1016/j.gassur.2025.102133

Abstract

Background: Gallbladder cancer (GBC) is an aggressive malignancy with poor prognosis due to its late-stage diagnosis and high recurrence rates after surgery. Neoadjuvant chemotherapy (NAC) has been explored as a strategy to improve resectability, downstage tumors, and target micro-metastatic disease. However, the efficacy of NAC remains inconclusive due to heterogeneous study designs. This meta-analysis evaluates the impact of NAC compared to upfront surgery on overall survival (OS) and disease-free survival (DFS) in GBC patients.

Methods: A systematic review was conducted following PRISMA guidelines (PROSPERO: CRD42024621395). PubMed, Embase, and Cochrane databases were searched for studies reporting on GBC patients receiving NAC followed by surgery or upfront surgery. Kaplan-Meier curves from studies were digitized and reconstructed, and a one-stage meta-analysis was performed. The primary objective was evaluating OS, while secondary objectives included evaluating DFS, postoperative complications, and surgical futility.

Results: Thirteen studies (n=6059) were included, with four studies comparing NAC to upfront surgery and nine single-arm studies evaluating NAC outcomes alone. NAC was associated with significantly improved OS (HR=0.54, 95%CI: 0.47; 0.62) compared to upfront surgery. DFS analysis showed a median of 42.9 months (95%CI: 33.9; 56) in NAC-treated patients. Postoperative complication rates were similar between groups, while the proportion of patients unable to proceed to surgery due to disease progression was lower in the NAC group (Proportion=0.16, 95%CI: 0.05; 0.38) than in the upfront surgery group (Proportion=0.27, 95%CI: 0.05; 0.73).

Conclusion: NAC in GBC is associated with an improved OS and reduced surgical futility without an increase in postoperative morbidity. These findings highlight the need for randomised controlled trials to validate NAC's role in treatment algorithms for resectable GBC.

Availability of data and materials: The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. The data includes this study's statistical analysis plan, and will be available with publication through emailing the corresponding author.

Keywords: Cancer; Chemotherapy; Gallbladder; Neoadjuvant.