• Pattraporn Tajarernmuang, Felipe Aliaga, Amr J Alwakeel, Gamuchirai Tavaziva, Kimberly Turner, Dick Menzies, Hangjun Wang, Linda Ofiara, Andrea Benedetti, and Anne V Gonzalez.
• Respiratory Epidemiology and Clinical Research Unit, Montreal Chest Institute, McGill University Health Centre, Montreal, QC, Canada; Respiratory, Critical Care and Allergy Division, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
• Chest. 2024 Feb 1; 165 (2): 461474461-474.

BackgroundProgrammed cell death ligand-1 (PD-L1) expression on tumor cells, evaluated by immunohistochemistry, guides the use of immunotherapy in advanced non-small cell lung cancer (NSCLC).Research QuestionWhat is the sensitivity and specificity of PD-L1 testing performed in cytologic vs paired histologic specimens in patients with NSCLC?Study Design And MethodsThe MEDLINE, Embase, Web of Science, and Cochrane Library databases were searched through June 1, 2021. The primary outcome was pooled sensitivity and specificity of PD-L1 testing performed on cytologic specimens compared with the reference standard of histologic specimens, analyzed at the PD-L1 expression cutoffs (tumor proportion score) ≥ 1% and ≥ 50%. Pooled sensitivity and specificity, and associated 95% CIs, were estimated using bivariate generalized linear mixed models.ResultsTwenty-six articles were included, encompassing a total of 1,064 pairs of histology specimens and cytology cell blocks, and 267 pairs of histology specimens and direct smears. Among these, 946 paired specimens were acquired without interval treatment between the collection of histology and cytology samples. The pooled sensitivity and specificity of cytology specimens compared with paired histology specimens at the PD-L1 expression cutoff ≥ 1% were 0.84 (95% CI, 0.77-0.89) and 0.88 (95% CI, 0.82-0.93), respectively, whereas the pooled sensitivity and specificity at cutoff ≥ 50% were 0.78 (95% CI, 0.69-0.86) and 0.94 (95% CI, 0.91-0.96), respectively. When only paired specimens acquired without interval treatment were considered, the pooled sensitivity and specificity of cytology specimens at PD-L1 expression cutoff ≥ 1% were 0.84 (95% CI, 0.76-0.90) and 0.89 (95% CI, 0.82-0.94), respectively, whereas the pooled sensitivity and specificity at cutoff ≥ 50% were 0.80 (95% CI, 0.71-0.89) and 0.94 (95% CI, 0.91-0.96), respectively.InterpretationCytologic specimens provide an accurate assessment of PD-L1 expression in most patients with NSCLC, at both ≥ 1% and ≥ 50% cutoffs, when compared with histologic specimens.Trial RegistrationPROSPERO; No.: CRD42020153279; URL: https://www.crd.york.ac.uk/prospero/.Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.

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