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Meta-Analysis
. 2025 Apr 23;20(4):e0295583.
doi: 10.1371/journal.pone.0295583. eCollection 2025.

Adjuvant chemotherapy compared with observation in patients with resected biliary tract cancer: A systematic review and meta-analysis of randomized controlled trials

Liying Tian  1 , Qian Guo  2 , Daidi Fu  3 , Xiao Ma  4 , Linjun Wang  1
Affiliations
Meta-Analysis

Adjuvant chemotherapy compared with observation in patients with resected biliary tract cancer: A systematic review and meta-analysis of randomized controlled trials

Liying Tian et al. PLoS One. .

Abstract

Objectives: Several randomized controlled trials compared adjuvant systemic chemotherapy with observation in patients with resected biliary tract cancer (BTC) have yielded inconsistent outcomes. In order to assess the efficacy of adjuvant therapy in these patients, we conducted this systematic review and meta-analysis.

Methods: We conducted a thorough search in various databases, which included MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, ASCO Abstracts, ESMO Abstracts and ClinicalTrials.gov. All relevant randomized controlled trials investigating the adjuvant chemotherapy compared with observation in resected biliary tract cancer were identified. The primary outcome of interest was overall survival (OS), while secondary outcome was relapse-free survival (RFS). Statistical analyses were conducted using Review Manager 5.3. Additionally, publication bias was evaluated using Egger's test in Stata 12.0.

Results: A total of 5 randomized controlled trials, involving 1406 patients, were included in this analysis. Compared with observation, adjuvant chemotherapy improved RFS [HR 0.84 (0.73-0.96), p=0.01] (I2=0%, p=0.89) but not OS [HR 0.89 (0.77-1.03), p=0.12] (I2=51%, p=0.09) in the entire population after BTC resection. Subgroup analyses revealed that adjuvant chemotherapy did improve both OS [HR 0.76 (0.62-0.93), p=0.009] (I2=7%, p=0.37) and RFS [HR 0.74 (0.58-0.95), p=0.02] (I2=0%, p=0.39) in patients with lymph node positivity. Furthermore, patients receiving oral fluoropyrimidine monotherapy showed benefit from the adjuvant therapy, with longer OS [HR 0.78 (0.65-0.94), p=0.009] (I2=2%, p=0.31) and RFS [HR 0.81 (0.68-0.95), p=0.01] (I2=0%, p=0.95).

Conclusions: To conclude, adjuvant chemotherapy have the potential to offer advantages in patients with resected BTC. Specifically, patients demonstrating positive lymph node status have a higher likelihood of benefiting from adjuvant therapy. Our analysis supports the current standard of care of adjuvant fluoropyrimidine. However, the recommendation of oral fluoropyrimidine monotherapy as the preferred option is not definitive, as it is based on limited studies. Further validation of these outcomes is necessary by conducting extensive randomized controlled trials.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Flow chart for identification and inclusion of studies for this meta-analysis.
Fig 2
Fig 2. Comparison of OS between adjuvant chemotherapy and observation.
SE: standard error. CI: Confidence interval. IV: Inverse variance.
Fig 3
Fig 3. Comparison of RFS between adjuvant chemotherapy and observation.
SE: standard error. CI: Confidence interval. IV: Inverse variance.
Fig 4
Fig 4. Publication bias shown in funnel plots.
See this image and copyright information in PMC

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