Prognostic Function of Programmed Cell Death-Ligand 1 in Esophageal Squamous Cell Carcinoma Patients Without Preoperative Therapy: A Systematic Review and Meta-Analysis

Background: Studies investigating the correlation between the expression of programmed cell death-ligand 1 (PD-L1) and prognosis in patients with esophageal squamous cell carcinoma (ESCC) not receiving preoperative therapy have increased significantly, but conclusions remain inconclusive. Therefore, this study aimed to determine the association between clinical outcomes and expression of PD-L1 in ESCC patients without preoperative therapy.

Methods: We conducted a comprehensive literature search using four databases up to May 2020. Quality assessment was carried out according to the Newcastle-Ottawa Quality Assessment Scale (NOS). Hazard ratios (HRs) were used to analyze the association between PD-L1 expression with prognosis. Furthermore, we evaluated the correlation between PD-L1 and clinicopathological characteristics using odds ratios (ORs) and 95% confidence intervals (CIs).

Results: Twenty studies (19 publications) comprising 3,677 patients were included in this meta-analysis. We found that the expression of PD-L1 was not related to overall survival (OS, HR: 1.16, 95% CI: 0.94-1.42, p = 0.16) or disease-free survival (DFS, HR: 0.85, 95% CI: 0.66-1.10, p = 0.21) in ESCC. Furthermore, although PD-L1 expression was not significantly associated with sex, degree of differentiation, TNM stage, T stage, lymph node status, smoking, or alcohol use, the merged OR demonstrated that the expression of PD-L1 was higher in older patients compared to younger patients (OR: 1.40, 95% CI: 1.07-1.83, p = 0.01). No obvious publication bias was observed.

Conclusions: Our present study illustrated that PD-L1 expression was not related to poor prognosis of ESCC patients not receiving preoperative therapy, albeit the association only showed a tendency for statistical significance. Notably, PD-L1 expression showed a significant association with age. This meta-analysis had several limitations; therefore, our results need to be verified through further large-scale and prospective studies.