Why PD-L1 expression varies between studies of lung cancer: results from a Bayesian meta-analysis
Abstract PD-L1 expression is an important biomarker for the management of non-small cell lung cancer (NSCLC) but has been highly heterogeneous across studies. We developed a statistical model to reconcile conflicting estimates of PD-L1 prevalence by accounting for between-study variation in test sen...
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Nature Portfolio
2025-02-01
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| Online Access: | https://doi.org/10.1038/s41598-024-80301-9 |
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| author | Preston Ngo Wendy A. Cooper Stephen Wade Kwun M. Fong Karen Canfell Deme Karikios Marianne Weber |
| author_facet | Preston Ngo Wendy A. Cooper Stephen Wade Kwun M. Fong Karen Canfell Deme Karikios Marianne Weber |
| author_sort | Preston Ngo |
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| description | Abstract PD-L1 expression is an important biomarker for the management of non-small cell lung cancer (NSCLC) but has been highly heterogeneous across studies. We developed a statistical model to reconcile conflicting estimates of PD-L1 prevalence by accounting for between-study variation in test sensitivity, specimen age, and laboratory count. In doing so, we obtained refined estimates for PD-L1 expression prevalence and identified differences by histological subtype, mutational status, and stage. Across 92 studies published between 2015 and 2023, the detectability of PD-L1 declined with increasing specimen age while the consistency of detection rates was greater for studies incorporating data from a higher number of laboratories. Using the 22C3 antibody as a benchmark, we predicted that 58.3% (95% CrI 49.8–66.1%) and 27.0% (95% CrI 21.2–33.1%) of NSCLC will have PD-L1 tumour proportion scores at the ≥ 1% and ≥ 50% threshold. PD-L1 expression was lower in EGFR-mutated NSCLC and higher in NSCLC with ALK, KRAS, MET, ROS1, and RET alterations. PD-L1 expression was more common with later-stage disease. Overall, this work highlights the continuing challenge of consistency in PD-L1 testing. Although the underlying prevalence of PD-L1 expression varies in the lung cancer population based on tumour-related factors, controllable differences in testing parameters also account for variations in PD-L1 prevalence. |
| format | Article |
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| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-02-01 |
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| spelling | doaj-art-ef9754f221bf4653a433ad41db09e4a72025-02-09T12:31:02ZengNature PortfolioScientific Reports2045-23222025-02-0115111010.1038/s41598-024-80301-9Why PD-L1 expression varies between studies of lung cancer: results from a Bayesian meta-analysisPreston Ngo0Wendy A. Cooper1Stephen Wade2Kwun M. Fong3Karen Canfell4Deme Karikios5Marianne Weber6The Daffodil Centre, The University of Sydney, A Joint Venture with the Cancer Council NSWDepartment of Tissue Pathology and Diagnostic Oncology, NSW Health Pathology, Royal Prince Alfred HospitalThe Daffodil Centre, The University of Sydney, A Joint Venture with the Cancer Council NSWPrince Charles HospitalThe Daffodil Centre, The University of Sydney, A Joint Venture with the Cancer Council NSWFaculty of Medicine and Health, University of SydneyThe Daffodil Centre, The University of Sydney, A Joint Venture with the Cancer Council NSWAbstract PD-L1 expression is an important biomarker for the management of non-small cell lung cancer (NSCLC) but has been highly heterogeneous across studies. We developed a statistical model to reconcile conflicting estimates of PD-L1 prevalence by accounting for between-study variation in test sensitivity, specimen age, and laboratory count. In doing so, we obtained refined estimates for PD-L1 expression prevalence and identified differences by histological subtype, mutational status, and stage. Across 92 studies published between 2015 and 2023, the detectability of PD-L1 declined with increasing specimen age while the consistency of detection rates was greater for studies incorporating data from a higher number of laboratories. Using the 22C3 antibody as a benchmark, we predicted that 58.3% (95% CrI 49.8–66.1%) and 27.0% (95% CrI 21.2–33.1%) of NSCLC will have PD-L1 tumour proportion scores at the ≥ 1% and ≥ 50% threshold. PD-L1 expression was lower in EGFR-mutated NSCLC and higher in NSCLC with ALK, KRAS, MET, ROS1, and RET alterations. PD-L1 expression was more common with later-stage disease. Overall, this work highlights the continuing challenge of consistency in PD-L1 testing. Although the underlying prevalence of PD-L1 expression varies in the lung cancer population based on tumour-related factors, controllable differences in testing parameters also account for variations in PD-L1 prevalence.https://doi.org/10.1038/s41598-024-80301-9PD-L1ImmunohistochemistryImmunotherapyBiomarkersNon-small cell lung cancer |
| spellingShingle | Preston Ngo Wendy A. Cooper Stephen Wade Kwun M. Fong Karen Canfell Deme Karikios Marianne Weber Why PD-L1 expression varies between studies of lung cancer: results from a Bayesian meta-analysis Scientific Reports PD-L1 Immunohistochemistry Immunotherapy Biomarkers Non-small cell lung cancer |
| title | Why PD-L1 expression varies between studies of lung cancer: results from a Bayesian meta-analysis |
| title_full | Why PD-L1 expression varies between studies of lung cancer: results from a Bayesian meta-analysis |
| title_fullStr | Why PD-L1 expression varies between studies of lung cancer: results from a Bayesian meta-analysis |
| title_full_unstemmed | Why PD-L1 expression varies between studies of lung cancer: results from a Bayesian meta-analysis |
| title_short | Why PD-L1 expression varies between studies of lung cancer: results from a Bayesian meta-analysis |
| title_sort | why pd l1 expression varies between studies of lung cancer results from a bayesian meta analysis |
| topic | PD-L1 Immunohistochemistry Immunotherapy Biomarkers Non-small cell lung cancer |
| url | https://doi.org/10.1038/s41598-024-80301-9 |
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