Clinicopathologic and Prognostic Significance of Programmed Cell Death Ligand 1 Expression in Patients with Non-Medullary Thyroid Cancer: A Systematic Review and Meta-Analysis

Background: Evidence has shown that programmed cell death ligand 1 (PD-L1) overexpression is associated with poor prognosis and resistance to immune therapies in several human cancers. However, data on the prognostic significance of PD-L1 expression in thyroid cancer are limited and remain controversial. This systematic review and meta-analysis aimed to evaluate comprehensively the clinicopathologic significance and prognostic value of PD-L1 expression in non-medullary thyroid cancers. Methods: Electronic databases, including Medline/PubMed, EMBASE, and the Cochrane Library, were searched up until July 5, 2017. In total, seven comparisons (from six articles) comprising 1421 patients were included in the pooled analysis. Results: There was moderate quality evidence from four studies (n=721) that shows positive PD-L1 expression was significantly associated with poor survival among thyroid cancer patients (pooled hazard ratio=3.73 [confidence interval (CI) 2.75-5.06]). Increased PD-L1 expression was also found to be significantly associated with disease recurrence (odds ratio=1.95 [CI 1.15-3.32]) and concurrent thyroiditis (odds ratio=1.65 [CI 1.09-2.51]). Conclusions: The results confirm the prognostic significance of PD-L1 expression in thyroid cancer patients. PD-L1 expression has the potential to be implemented as a prognostic biomarker used to guide clinicians in identifying patients with more aggressive cancers, and for the selection of individuals that would derive durable clinical benefit from anti-PD-1/PD-L1 immunotherapy. Prospective clinical trials will be useful to support these findings.