A Retrospective Evaluation of PD-L1 Expression and Heterogeneity in Early-Stage Non-Small Cell Lung Cancer (REPLICA)

Eleni C. Josephides; Daniel Smith; Andrea Bille; Akshay Patel; Hannah L. Rush; Roberta Dunn; Daniel J. Hughes; Sarah Hunter; Phillipe Taniere; Danielle Crawley; Maria Monroy-Iglesias; Annie Rose Henry; Ana Montes; Mieke Van Hemelrijck; James Spicer; Debra Josephs; George Santis; Daisuke Nonaka; Eleni M. Karapanagiotou

doi:10.1016/j.cllc.2025.01.008

A Retrospective Evaluation of PD-L1 Expression and Heterogeneity in Early-Stage Non-Small Cell Lung Cancer (REPLICA)

Eleni C. Josephides
, Daniel Smith
, Andrea Bille
, Akshay Patel
, Hannah L. Rush
, Roberta Dunn
, Daniel J. Hughes
, Sarah Hunter
, Phillipe Taniere
, Danielle Crawley
, Maria Monroy-Iglesias
, Annie Rose Henry
, Ana Montes
, Mieke Van Hemelrijck
, James Spicer
, Debra Josephs
, George Santis
, Daisuke Nonaka
, Eleni M. Karapanagiotou^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

2 Citations (Scopus)

Abstract

Background: Immune checkpoint inhibitors have improved survival in patients with non-small cell lung cancer (NSCLC). Whilst PD-L1 expression is a useful predictive biomarker, data on concordance of expression between primary tumor and nodal metastases in the surgical setting are sparse. Methods: We assessed PD-L1 expression in paired primary tumor and involved lymph node samples from 451 consecutive patients with stage IIB-IIIB NSCLC who underwent curative lung resection and lymphadenectomy at our institution between 2009 and 2018, to assess intertumor heterogeneity. Clinical records were examined to determine survival outcomes, and relationship to PD-L1 expression was explored. Results: Using PD-L1 expression categories of < 1%, 1% to 49% and ≥ 50% there was heterogeneity of PD-L1 expression between the primary and corresponding lymph node metastases in 24% of cases with only moderate positive correlation (Spearman's coefficient 0.7). 46% of early-stage primary tumors expressed PD-L1, although only 11% demonstrated a high (> 50%) level. It was more common for PD-L1 expression to be higher in the primary tumor than its metastatic lymph node than the converse. PD-L1 expression irrespective of site, had no significant impact on disease-free or overall survival. Conclusion: Our study confirms the heterogeneity of PD-L1 expression in early-stage NSCLC and suggests that a biopsy specimen from a single site may not be a comprehensive representation of PD-L1 expression. The proportion of tumours with high PD-L1 expression appears lower in early-stage NSCLC than in advanced disease.

Original language	English
Pages (from-to)	e223-e231
Journal	Clinical Lung Cancer
Volume	26
Issue number	3
Early online date	26 Apr 2025
DOIs	https://doi.org/10.1016/j.cllc.2025.01.008
Publication status	Published - May 2025

Keywords

Biopsy specimen
Immunotherapy
Intertumoral heterogeneity
Lymph nodes
Surgery

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.cllc.2025.01.008

Cite this

Josephides, E. C., Smith, D., Bille, A., Patel, A., Rush, H. L., Dunn, R., Hughes, D. J., Hunter, S., Taniere, P., Crawley, D., Monroy-Iglesias, M., Henry, A. R., Montes, A., Van Hemelrijck, M., Spicer, J., Josephs, D., Santis, G., Nonaka, D., & Karapanagiotou, E. M. (2025). A Retrospective Evaluation of PD-L1 Expression and Heterogeneity in Early-Stage Non-Small Cell Lung Cancer (REPLICA). Clinical Lung Cancer, 26(3), e223-e231. https://doi.org/10.1016/j.cllc.2025.01.008

@article{2ad05c2091eb4ada8ead201b744a3f53,

title = "A Retrospective Evaluation of PD-L1 Expression and Heterogeneity in Early-Stage Non-Small Cell Lung Cancer (REPLICA)",

abstract = "Background: Immune checkpoint inhibitors have improved survival in patients with non-small cell lung cancer (NSCLC). Whilst PD-L1 expression is a useful predictive biomarker, data on concordance of expression between primary tumor and nodal metastases in the surgical setting are sparse. Methods: We assessed PD-L1 expression in paired primary tumor and involved lymph node samples from 451 consecutive patients with stage IIB-IIIB NSCLC who underwent curative lung resection and lymphadenectomy at our institution between 2009 and 2018, to assess intertumor heterogeneity. Clinical records were examined to determine survival outcomes, and relationship to PD-L1 expression was explored. Results: Using PD-L1 expression categories of < 1\%, 1\% to 49\% and ≥ 50\% there was heterogeneity of PD-L1 expression between the primary and corresponding lymph node metastases in 24\% of cases with only moderate positive correlation (Spearman's coefficient 0.7). 46\% of early-stage primary tumors expressed PD-L1, although only 11\% demonstrated a high (> 50\%) level. It was more common for PD-L1 expression to be higher in the primary tumor than its metastatic lymph node than the converse. PD-L1 expression irrespective of site, had no significant impact on disease-free or overall survival. Conclusion: Our study confirms the heterogeneity of PD-L1 expression in early-stage NSCLC and suggests that a biopsy specimen from a single site may not be a comprehensive representation of PD-L1 expression. The proportion of tumours with high PD-L1 expression appears lower in early-stage NSCLC than in advanced disease.",

keywords = "Biopsy specimen, Immunotherapy, Intertumoral heterogeneity, Lymph nodes, Surgery",

author = "Josephides, \{Eleni C.\} and Daniel Smith and Andrea Bille and Akshay Patel and Rush, \{Hannah L.\} and Roberta Dunn and Hughes, \{Daniel J.\} and Sarah Hunter and Phillipe Taniere and Danielle Crawley and Maria Monroy-Iglesias and Henry, \{Annie Rose\} and Ana Montes and \{Van Hemelrijck\}, Mieke and James Spicer and Debra Josephs and George Santis and Daisuke Nonaka and Karapanagiotou, \{Eleni M.\}",

note = "Publisher Copyright: {\textcopyright} 2025 Elsevier Inc.",

year = "2025",

month = may,

doi = "10.1016/j.cllc.2025.01.008",

language = "English",

volume = "26",

pages = "e223--e231",

journal = "Clinical Lung Cancer",

issn = "1525-7304",

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Josephides, EC, Smith, D, Bille, A, Patel, A, Rush, HL, Dunn, R, Hughes, DJ, Hunter, S, Taniere, P, Crawley, D , Monroy-Iglesias, M, Henry, AR, Montes, A, Van Hemelrijck, M , Spicer, J , Josephs, D , Santis, G, Nonaka, D & Karapanagiotou, EM 2025, 'A Retrospective Evaluation of PD-L1 Expression and Heterogeneity in Early-Stage Non-Small Cell Lung Cancer (REPLICA)', Clinical Lung Cancer, vol. 26, no. 3, pp. e223-e231. https://doi.org/10.1016/j.cllc.2025.01.008

TY - JOUR

T1 - A Retrospective Evaluation of PD-L1 Expression and Heterogeneity in Early-Stage Non-Small Cell Lung Cancer (REPLICA)

AU - Josephides, Eleni C.

AU - Smith, Daniel

AU - Bille, Andrea

AU - Patel, Akshay

AU - Rush, Hannah L.

AU - Dunn, Roberta

AU - Hughes, Daniel J.

AU - Hunter, Sarah

AU - Taniere, Phillipe

AU - Crawley, Danielle

AU - Monroy-Iglesias, Maria

AU - Henry, Annie Rose

AU - Montes, Ana

AU - Van Hemelrijck, Mieke

AU - Spicer, James

AU - Josephs, Debra

AU - Santis, George

AU - Nonaka, Daisuke

AU - Karapanagiotou, Eleni M.

PY - 2025/5

Y1 - 2025/5

N2 - Background: Immune checkpoint inhibitors have improved survival in patients with non-small cell lung cancer (NSCLC). Whilst PD-L1 expression is a useful predictive biomarker, data on concordance of expression between primary tumor and nodal metastases in the surgical setting are sparse. Methods: We assessed PD-L1 expression in paired primary tumor and involved lymph node samples from 451 consecutive patients with stage IIB-IIIB NSCLC who underwent curative lung resection and lymphadenectomy at our institution between 2009 and 2018, to assess intertumor heterogeneity. Clinical records were examined to determine survival outcomes, and relationship to PD-L1 expression was explored. Results: Using PD-L1 expression categories of < 1%, 1% to 49% and ≥ 50% there was heterogeneity of PD-L1 expression between the primary and corresponding lymph node metastases in 24% of cases with only moderate positive correlation (Spearman's coefficient 0.7). 46% of early-stage primary tumors expressed PD-L1, although only 11% demonstrated a high (> 50%) level. It was more common for PD-L1 expression to be higher in the primary tumor than its metastatic lymph node than the converse. PD-L1 expression irrespective of site, had no significant impact on disease-free or overall survival. Conclusion: Our study confirms the heterogeneity of PD-L1 expression in early-stage NSCLC and suggests that a biopsy specimen from a single site may not be a comprehensive representation of PD-L1 expression. The proportion of tumours with high PD-L1 expression appears lower in early-stage NSCLC than in advanced disease.

AB - Background: Immune checkpoint inhibitors have improved survival in patients with non-small cell lung cancer (NSCLC). Whilst PD-L1 expression is a useful predictive biomarker, data on concordance of expression between primary tumor and nodal metastases in the surgical setting are sparse. Methods: We assessed PD-L1 expression in paired primary tumor and involved lymph node samples from 451 consecutive patients with stage IIB-IIIB NSCLC who underwent curative lung resection and lymphadenectomy at our institution between 2009 and 2018, to assess intertumor heterogeneity. Clinical records were examined to determine survival outcomes, and relationship to PD-L1 expression was explored. Results: Using PD-L1 expression categories of < 1%, 1% to 49% and ≥ 50% there was heterogeneity of PD-L1 expression between the primary and corresponding lymph node metastases in 24% of cases with only moderate positive correlation (Spearman's coefficient 0.7). 46% of early-stage primary tumors expressed PD-L1, although only 11% demonstrated a high (> 50%) level. It was more common for PD-L1 expression to be higher in the primary tumor than its metastatic lymph node than the converse. PD-L1 expression irrespective of site, had no significant impact on disease-free or overall survival. Conclusion: Our study confirms the heterogeneity of PD-L1 expression in early-stage NSCLC and suggests that a biopsy specimen from a single site may not be a comprehensive representation of PD-L1 expression. The proportion of tumours with high PD-L1 expression appears lower in early-stage NSCLC than in advanced disease.

KW - Biopsy specimen

KW - Immunotherapy

KW - Intertumoral heterogeneity

KW - Lymph nodes

KW - Surgery

UR - https://www.scopus.com/pages/publications/85217061087

U2 - 10.1016/j.cllc.2025.01.008

DO - 10.1016/j.cllc.2025.01.008

M3 - Article

C2 - 39915192

AN - SCOPUS:85217061087

SN - 1525-7304

VL - 26

SP - e223-e231

JO - Clinical Lung Cancer

JF - Clinical Lung Cancer

IS - 3

ER -

A Retrospective Evaluation of PD-L1 Expression and Heterogeneity in Early-Stage Non-Small Cell Lung Cancer (REPLICA)

Abstract

Keywords

UN SDGs

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