Prognostic significance of programmed cell death‐ligand 1 expression on circulating tumor cells in various cancers: A systematic review and meta‐analysis

Background The prognostic significance of programmed cell death‐ligand 1 (PD‐L1) expression on circulating tumor cells (CTCs) has been explored but is still in controversy. We performed, for the first time, a meta‐analysis to systematically evaluate its prognostic value in human cancers. Methods Literature databases were searched for eligible studies prior to June 30, 2021. The pooled hazard ratios (HRs) and 95% confidence intervals (95% CIs) were calculated for the associations of pre‐treatment and post‐treatment PD‐L1+ CTCs with progression‐free survival (PFS) and overall survival (OS). Subgroup analyses with regards to cancer type, treatment, CTC enrichment method, PD‐L1 detection method, cut‐off, and specifically the comparison model were performed. Results We included 30 eligible studies (32 cohorts, 1419 cancer patients) in our analysis. Pre‐treatment PD‐L1+ CTCs detected by immunofluorescence (IF) tended to predict better PFS (HR = 0.55, 95% CI 0.28–1.08, p = 0.084) and OS (HR = 0.61, 95% CI 0.36–1.04, p = 0.067) for immune checkpoint inhibitor (ICI) treatment, but were significantly associated with unfavorable survival for non‐ICI therapies (PFS: HR = 1.85, 95% CI 1.21–2.85, p = 0.005; OS: HR = 2.44, 95% CI 1.69–3.51, p
Meta‐analysis shows that positive expression of PD‐L1 on circulating tumor cells predicts better survival prognosis in cancer patients treated with immune checkpoint inhibitors but unfavorable survival in those treated with other therapies. PD‐L1 expression on CTCs may be a promising prognostic marker for tumor treatment.