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Background <p>Programmed death-ligand 1 (PD-L1) expression has emerged as a potential predictive biomarker for immunotherapy response in esophageal cancer (EC). However, its clinical utility as a biomarker is influenced by variability in detection methods, scoring systems, and positivity thresholds, leading to inconsistent interpretations across studies. This meta-analysis aims to evaluate the role of PD-L1 expression as a predictive biomarker in EC.</p> Methods <p>A systematic search was conducted in PubMed, Google Scholar, Embase, Cochrane, and Web of Science up to November 6, 2024. Studies evaluating PD-L1 expression in EC and its correlation with survival outcomes were included. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using random- or fixed-effects models. Study registration: Prospero ID ( CRD420251046175).</p> Results <p>The meta-analysis included 31 studies (5,121 patients). The pooled analysis revealed a significant association between high PD-L1 expression and worse overall survival (OS) (HR = 1.87, 95% CI: 1.11–3.17, <i>P</i> = 0.02). However, this result was accompanied by extreme heterogeneity (I² = 98%, <i>P</i> &lt; 0.00001). For disease-free survival (DFS), a secondary analysis demonstrated a trend toward poorer outcomes with PD-L1 positivity (HR = 1.44, 95% CI: 0.97–2.14, <i>P</i> = 0.08), though statistical significance was not reached. Substantial heterogeneity was observed (I² = 82%).</p> Conclusion <p>This analysis suggests an association between high PD-L1 expression and worse OS in EC. However, the extreme heterogeneity observed, likely stemming from variability in PD-L1 assessment methods and patient populations, indicates that this relationship is context-dependent and not universally generalizable. These findings highlight the urgent need for standardized evaluation protocols to establish PD-L1 as a reliable prognostic marker in clinical practice.</p>

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The Role of PD-L1 Expression as a Predictive Biomarker in Esophageal Cancer: a Meta-Analysis

  • 期刊论文

  • 发表日期：

    2026年2月25日

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  • Acquah Theophilus,
  • Zakari Shaibu,
  • Jie Ma

摘要

Background

Programmed death-ligand 1 (PD-L1) expression has emerged as a potential predictive biomarker for immunotherapy response in esophageal cancer (EC). However, its clinical utility as a biomarker is influenced by variability in detection methods, scoring systems, and positivity thresholds, leading to inconsistent interpretations across studies. This meta-analysis aims to evaluate the role of PD-L1 expression as a predictive biomarker in EC.

Methods

A systematic search was conducted in PubMed, Google Scholar, Embase, Cochrane, and Web of Science up to November 6, 2024. Studies evaluating PD-L1 expression in EC and its correlation with survival outcomes were included. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using random- or fixed-effects models. Study registration: Prospero ID ( CRD420251046175).

Results

The meta-analysis included 31 studies (5,121 patients). The pooled analysis revealed a significant association between high PD-L1 expression and worse overall survival (OS) (HR = 1.87, 95% CI: 1.11–3.17, P = 0.02). However, this result was accompanied by extreme heterogeneity (I² = 98%, P < 0.00001). For disease-free survival (DFS), a secondary analysis demonstrated a trend toward poorer outcomes with PD-L1 positivity (HR = 1.44, 95% CI: 0.97–2.14, P = 0.08), though statistical significance was not reached. Substantial heterogeneity was observed (I² = 82%).

Conclusion

This analysis suggests an association between high PD-L1 expression and worse OS in EC. However, the extreme heterogeneity observed, likely stemming from variability in PD-L1 assessment methods and patient populations, indicates that this relationship is context-dependent and not universally generalizable. These findings highlight the urgent need for standardized evaluation protocols to establish PD-L1 as a reliable prognostic marker in clinical practice.