Discordance of PD-L1 expression between primary and paired metastatic non-small cell lung cancer: a systematic review and meta-analysis
- 1Department of Pathology, China-Japan Union Hospital of Jilin University
- 2Science Research Center, China-Japan Union Hospital of Jilin University
Abstract
Background: PD-L1 expression in non-small cell lung cancer (NSCLC) serves as a key predictive biomarker of response to immune checkpoint inhibitors; however, the concordance of PD-L1 expression between primary tumors and their corresponding metastatic lesions remains uncertain. We therefore performed a systematic review and meta-analysis to evaluate the variability of PD-L1 expression across paired primary and metastatic NSCLC sites.
Methods: We systematically searched the Cochrane Library, Embase, PubMed, and Web of Science for eligible studies. Pooled discordance rates and patterns of mismatch were estimated using a random-effects model, and subgroup analyses were conducted according to PD-L1 cutoff, antibody clone, and metastatic site.
Results: Fifteen studies fulfilled the inclusion criteria, encompassing 1,029 matched primary–metastatic sample pairs from 1,014 patients with NSCLC. The pooled analysis revealed an overall PD-L1 discordance rate of 21% between primary tumors and corresponding metastases (95% CI: 18%–25%). Notably, transitions from PD-L1-positive primary tumors to PD-L1-negative metastatic lesions occurred more frequently (26%, 95% CI: 22%–30%) than the reverse pattern, from negative primaries to positive metastases (18%, 95% CI: 12%–24%). Discordance of similar magnitude was observed across PD-L1 positivity thresholds and antibody clones and in both lymph node and brain metastases, although the site-specific estimates are exploratory.
Discussion: In patients with NSCLC, PD-L1 expression frequently differs between primary and metastatic lesions, with a greater tendency for expression to decrease at metastatic sites. These findings indicate that PD-L1 results obtained from an archival primary tumor should be interpreted with caution when they are used to inform treatment of metastatic disease. Whether repeat testing of metastatic tissue improves patient selection or immunotherapy outcomes has not been demonstrated and requires prospective evaluation.
Systematic review registration: https://www.crd.york.ac.uk/PROSPERO , identifier CRD42022336191.
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BibTeX
@article{zhang2026discordance,
title = {{Discordance of PD-L1 expression between primary and paired metastatic non-small cell lung cancer: a systematic review and meta-analysis}},
author = {Leichao Zhang and Yiyao Gao and Xuemei Wang and Yu Gu and Lijian Hou and Xueju Wang},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1942041},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1942041/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Discordance of PD-L1 expression between primary and paired metastatic non-small cell lung cancer: a systematic review and meta-analysis
AU - Leichao Zhang
AU - Yiyao Gao
AU - Xuemei Wang
AU - Yu Gu
AU - Lijian Hou
AU - Xueju Wang
PY - 2026
DA - 2026/10/20
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1942041
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1942041/full
AB - Background: PD-L1 expression in non-small cell lung cancer (NSCLC) serves as a key predictive biomarker of response to immune checkpoint inhibitors; however, the concordance of PD-L1 expression between primary tumors and their corresponding metastatic lesions remains uncertain. We therefore performed a systematic review and meta-analysis to evaluate the variability of PD-L1 expression across paired primary and metastatic NSCLC sites. Methods: We systematically searched the Cochrane Library, Embase, PubMed, and Web of Science for eligible studies. Pooled discordance rates and patterns of mismatch were estimated using a random-effects model, and subgroup analyses were conducted according to PD-L1 cutoff, antibody clone, and metastatic site. Results: Fifteen studies fulfilled the inclusion criteria, encompassing 1,029 matched primary–metastatic sample pairs from 1,014 patients with NSCLC. The pooled analysis revealed an overall PD-L1 discordance rate of 21% between primary tumors and corresponding metastases (95% CI: 18%–25%). Notably, transitions from PD-L1-positive primary tumors to PD-L1-negative metastatic lesions occurred more frequently (26%, 95% CI: 22%–30%) than the reverse pattern, from negative primaries to positive metastases (18%, 95% CI: 12%–24%). Discordance of similar magnitude was observed across PD-L1 positivity thresholds and antibody clones and in both lymph node and brain metastases, although the site-specific estimates are exploratory. Discussion: In patients with NSCLC, PD-L1 expression frequently differs between primary and metastatic lesions, with a greater tendency for expression to decrease at metastatic sites. These findings indicate that PD-L1 results obtained from an archival primary tumor should be interpreted with caution when they are used to inform treatment of metastatic disease. Whether repeat testing of metastatic tissue improves patient selection or immunotherapy outcomes has not been demonstrated and requires prospective evaluation. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO , identifier CRD42022336191.
SN - 1664-3224
ER -