Discordance in PD-L1 scores on repeat testing of non-small cell lung carcinomas

Abstract

Introduction: PD-L1 expression may be used as a biomarker predictive of non-small cell lung carcinoma (NSCLC) response to PD-L1 inhibitor treatment. Spatial and temporal heterogeneity in PD-L1 expression and variation in PD-L1 test interpretation may contribute to differences in PD-L1 test results between samples of the same patient's disease.

Methods: Retrospective chart review identified 77 NSCLC patients with 22C3 PharmDx PD-L1 assays performed on two different tumor samples. Patients clinically suspected to have two separate primaries were excluded. PD-L1 test results in different score categories (<1%, 1-49% and ≥50%) were considered discordant. Clinical and pathologic factors associated with discordance were assessed.

Results: 28 (36%) of the 77 cases had discordant PD-L1 scores between samples. Patients with an initial test result of 1-49% were most likely to have a discordant second test result. Specimen type (cytology, small biopsy or resection), specimen site (lung, lymph node, pleura/pleural effusion or distant metastasis), time between specimen collection, and treatment between specimen collection were not significantly associated with the rate of discordance.

Conclusions: Repeat PD-L1 testing of the same patient's NSCLC results frequently resulted in discordant test results, independent of whether the samples differed in clinical or pathologic factors. This discordance rate underscores the extent to which PD-L1 levels are heterogeneous and difficult to accurately represent with a single test value. Further study of the predictive value of PD-L1 scores in cases with discordant results is needed.

Keywords: Biomarkers; Molecular pathology; Non-small cell lung carcinoma; PD-L1.