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

<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.

**引言：** 程序性死亡配体1（Programmed death-ligand 1，PD-L1）的表达可用于非小细胞肺癌（non-small cell lung cancer，NSCLC）的治疗预测。尽管在常规临床实践中，细胞学样本可能是唯一可获取的检测材料，但临床试验中的PD-L1检测主要以活检组织样本为基础。
**方法：** 本研究纳入两个回顾性队列，均包含配对的、同期采集的细胞学样本与活检组织样本。同时，本研究对已发表的关于配对细胞学/组织学样本中PD-L1表达的相关文献进行了系统回顾，分析重点聚焦于肿瘤细胞阳性率≥1%与≥50%这两个截断值。
**结果：** 采用三级评分量表进行评估时，两个队列中配对非小细胞肺癌样本的PD-L1表达一致性分别为40/47（85%）与66/97（68%），对应的科恩κ值分别为0.77与0.49。在第一个队列中，所有不一致病例的细胞学样本PD-L1评分均低于活检组织样本。在两个队列中，取材部位不同的样本（如原发肿瘤活检样本与胸腔积液细胞学样本）的一致性均更低。基于涵盖约1700例配对细胞学/组织学样本的25项已发表研究，当PD-L1染色阳性截断值为1%时，一致性的中位数（范围）为81%~85%（62%~100%）；当截断值为50%时，一致性中位数为89%（67%~100%）。
**结论：** 细胞学样本与活检组织样本的PD-L1表达整体一致性较好，但不同实验室间存在显著差异，因此需要开展本地化的质量保证工作。