title: PD-L1 testing for lung cancer in the UK: recognizing the challenges for implementation.
abstract: A new approach to the management of non-small-cell lung cancer (NSCLC) has recently emerged that works by manipulating the immune checkpoint controlled by programmed death receptor 1 (PD-1) and its ligand programmed death ligand 1 (PD-L1). Several drugs targeting PD-1 (pembrolizumab and nivolumab) or PD-L1 (atezolizumab, durvalumab, and avelumab) have been approved or are in the late stages of development. Inevitably, the introduction of these drugs will put pressure on healthcare systems, and there is a need to stratify patients to identify those who are most likely to benefit from such treatment. There is evidence that responsiveness to PD-1 inhibitors may be predicted by expression of PD-L1 on neoplastic cells. Hence, there is considerable interest in using PD-L1 immunohistochemical staining to guide the use of PD-1-targeted treatments in patients with NSCLC. This article reviews the current knowledge about PD-L1 testing, and identifies current research requirements. Key factors to consider include the source and timing of sample collection, pre-analytical steps (sample tracking, fixation, tissue processing, sectioning, and tissue prioritization), analytical decisions (choice of biomarker assay/kit and automated staining platform, with verification of standardized assays or validation of laboratory-devised techniques, internal and external quality assurance, and audit), and reporting and interpretation of the results. This review addresses the need for integration of PD-L1 immunohistochemistry with other tests as part of locally agreed pathways and protocols. There remain areas of uncertainty, and guidance should be updated regularly as new information becomes available.
authors.affiliation: Department of Pathology, University Hospitals Coventry and Warwickshire NHS Trust, Coventry, UK.
authors.forename: Ian A
authors.initials: IA
authors.lastname: Cree
authors.affiliation: Respiratory and Allergy Research Group, Institute of Inflammation & Repair, North West Lung Centre, University of Manchester, University Hospital of South Manchester NHS Foundation Trust, Manchester, UK.
authors.forename: Richard
authors.initials: R
authors.lastname: Booton
authors.affiliation: Department of Histopathology, Guy's and St Thomas' NHS Foundation Trust, London, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Cane
authors.affiliation: Department of Pathology, Royal Liverpool and Broadgreen University Hospitals NHS Trust, Liverpool, UK.
authors.forename: John
authors.initials: J
authors.lastname: Gosney
authors.affiliation: UK National External Quality Assessment Service for Immunocytochemistry and In Situ Hybridisation, London, UK.
authors.forename: Merdol
authors.initials: M
authors.lastname: Ibrahim
authors.affiliation: Department of Pathology, Aberdeen Royal Infirmary/Aberdeen University Medical School, Aberdeen, UK.
authors.forename: Keith
authors.initials: K
authors.lastname: Kerr
authors.affiliation: Guy's and St Thomas' NHS Foundation Trust, London, UK.
authors.forename: Rohit
authors.initials: R
authors.lastname: Lal
authors.affiliation: Oncology Department, Charing Cross Hospital, Imperial College Healthcare NHS Trust, London, UK.
authors.forename: Conrad
authors.initials: C
authors.lastname: Lewanski
authors.affiliation: Lungs for Living Research Centre, UCL Respiratory, University College London Hospitals NHS Foundation Trust, London, UK.
authors.forename: Neal
authors.initials: N
authors.lastname: Navani
authors.affiliation: Royal Brompton and Harefield Hospitals NHS Foundation Trust and National Heart and Lung Division, Imperial College, London, UK.
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Nicholson
authors.affiliation: Department of Oncology, NHS Grampian, Aberdeen Royal Infirmary, Aberdeen, UK.
authors.forename: Marianne
authors.initials: M
authors.lastname: Nicolson
authors.affiliation: The Christie Hospital NHS Foundation Trust, Manchester, UK.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Summers
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D060890:B7-H1 Antigen / Q000187:drug effects / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis* / Q000188:drug therapy / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000188:drug therapy / Q000378:metabolism; D000077594:Nivolumab; D061026:Programmed Cell Death 1 Receptor / Q000187:drug effects / Q000378:metabolism; D011786:Quality Control
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D060890:B7-H1 Antigen; D014408:Biomarkers, Tumor; C423236:CD274 protein, human; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D000077594:Nivolumab; C582435:pembrolizumab
keywords: immunohistochemistry; immunotherapy; non-small-cell lung cancer; programmed death ligand 1; programmed death receptor 1; quality assurance; specimen handling; treatment stratification