Immune checkpoint inhibitors targeting the programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) pathway improve clinical outcomes in patients with locally advanced/metastatic urothelial carcinoma (UC). PD-L1 complementary or companion diagnostic assays are now available for anti-PD-1 and anti-PD-L1 antibodies and these assays enable testing at diagnosis. The role of PD-L1 testing in UC is, however, the subject of much discussion within the medical community, particularly in light of recent restrictions on recruitment of PD-L1-low patients in clinical trials of atezolizumab and pembrolizumab as first-line therapy, and the European Medicines Agency and US Food and Drug Administration limiting use of these agents as first-line therapy in cisplatin-ineligible patients to those with high PD-L1 expression. We explore the evolving evidence for PD-L1 expression testing in UC and the role of PD-L1 expression in both tumor cells and tumor-infiltrating immune cells. We review clinical data on the prognostic and predictive value of PD-L1 expression in response to anti-PD-1/PD-L1 agents as first- and second-line therapy, considering issues such as the differences among complementary diagnostic assays in terms of the type of cells scored, antibodies used, and cutoff values. We consider how PD-L1 testing fits into decision-making and the potential of emerging biomarkers in UC. We conclude that, based on the scientific rationale for its use and evidence from clinical trials, PD-L1 testing provides enriched information on the patients most likely to benefit from immune checkpoint blockade and should be routinely offered to patients with metastatic UC.

中文翻译：

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PD-L1检测在转移性尿路上皮癌患者中的作用不断演变。

靶向程序性细胞死亡1（PD-1）/程序性细胞死亡配体1（PD-L1）途径的免疫检查点抑制剂可改善局部晚期/转移性尿路上皮癌（UC）患者的临床结局。PD-L1互补或伴随诊断测定现已可用于抗PD-1和抗PD-L1抗体，这些测定可在诊断时进行测试。然而，PD-L1检测在UC中的作用是医学界广泛讨论的主题，特别是考虑到最近在atezolizumab和pembrolizumab作为一线治疗的临床试验中招募PD-L1低患者的近期限制，以及欧洲药品管理局和美国食品和药物管理局（US Food and Drug Administration）将这些药物作为不适合顺铂治疗的患者的一线治疗，仅限于PD-L1高表达的患者。我们探讨了PD-L1在UC中的表达测试的不断发展的证据以及PD-L1在肿瘤细胞和肿瘤浸润性免疫细胞中的表达。我们回顾了有关抗PD-1 / PD-L1药物作为一线和二线治疗的PD-L1表达的预后和预测价值的临床数据，考虑了诸如互补诊断分析之间的差异等问题。评分的细胞类型，使用的抗体和截止值。我们考虑PD-L1测试如何适应决策以及UC中新兴生物标志物的潜力。我们得出结论，基于其使用的科学原理和来自临床试验的证据，PD-L1检测可提供有关最有可能从免疫检查点封锁中获益的患者的丰富信息，应常规向转移性UC患者提供。