PD-L1 Testing in Cytological Non-Small Cell Lung Cancer Specimens: A Comparison with Biopsies and Review of the Literature

Abstract

<b><i>Introduction:</i></b> Programmed death-ligand 1 (PD-L1) expression is used for treatment prediction in non-small cell lung cancer (NSCLC). While cytology may be the only available material in the routine clinical setting, testing in clinical trials has mainly been based on biopsies. <b><i>Methods:</i></b> We included 2 retrospective cohorts of paired, concurrently sampled, cytological specimens and biopsies. Also, the literature on PD-L1 in paired cytological/histological samples was reviewed. Focus was on the cutoff levels ≥1 and ≥50% positive tumor cells. <b><i>Results:</i></b> Using a 3-tier scale, PD-L1 was concordant in 40/47 (85%) and 66/97 (68%) of the paired NSCLC cases in the 2 cohorts, with kappa 0.77 and 0.49, respectively. In the former cohort, all discordant cases had lower score in cytology. In both cohorts, concordance was lower in samples from different sites (e.g., biopsy from primary tumor and cytology from pleural effusion). Based on 25 published studies including about 1,700 paired cytology/histology cases, the median (range) concordance was 81–85% (62–100%) at cutoff 1% for a positive PD-L1 staining and 89% (67–100%) at cutoff 50%. <b><i>Conclusions:</i></b> The overall concordance of PD-L1 between cytology and biopsies is rather good but with significant variation between laboratories, which calls for local quality assurance.

Factors Influencing Concordance of PD-L1 Expression between Biopsies and Cytological Specimens in Non-Small Cell Lung Cancer

“…In our previous study, we compared PD-L1 expression between histology and cytology in two different cohorts in southern Sweden [20]. We found a slightly lower rate of concordance in one of the cohorts, and in the present study, we further analysed that cohort regarding the impact of preanalytical factors on the concordance between biopsies and cytological specimens.…”

“…As cytological specimens are handled differently, both compared to biopsies and between pathology departments, there is a need to evaluate cytology for reliability of PD-L1. Studies investigating the predictive value of PD-L1 on cytology in an immunotherapy-treated population are rare [31], while today, there is quite substantial data on PD-L1 staining in paired histological and cytological cases [19,20].…”

“…PD-L1 staining with the 28-8 assay (see below) had either been performed in the clinical setting or the specimens identically stained as part of the present study. For 83 (17 PE, 13 BB, and 53 BAL) of the cases, the paired specimens were included in a previous study [20].…”

“…Preparation and staining of specimens were consistent over time and has previously been described [20]. In brief, the cell blocks were routinely available together with smears and ThinPrep ® slides in the clinical setting.…”

“…The suitability of cytology for PD-L1 testing has been discussed [16][17][18], and the lack of comprehensive data and validation has prevented wide acceptance. PD-L1 expression in paired histological and cytological materials from NSCLC patients has been compared in several studies [19,20]. The overall agreement of PD-L1 reactivity has been reported to be relatively good between histology and cytology but with substantial variation between studies, both for concordance and proportion of positive PD-L1 NSCLC in cytological specimens.…”