Retrospective evaluation of plasma protein tumour markers for early lung cancer detection

Michael Peter Alan Davies; Ruwanthi Kolamunnage-Dona; Suzannah Phillips; Angela Lambert; Stephanie Tate; John Kirkpatrick Field

doi:10.1038/s44276-024-00082-6

Retrospective evaluation of plasma protein tumour markers for early lung cancer detection

BJC Rep. 2024 Aug 19;2(1):59. doi: 10.1038/s44276-024-00082-6.

Authors

Michael Peter Alan Davies¹, Ruwanthi Kolamunnage-Dona², Suzannah Phillips³, Angela Lambert³, Stephanie Tate⁴, John Kirkpatrick Field⁴

Affiliations

¹ Department of Molecular and Clinical Cancer Medicine, Institute of Systems, Molecular & Integrative Biology, The University of Liverpool, Liverpool, UK. [email protected].
² Department of Health and Data Science, Institute of Population Health, The University of Liverpool, Liverpool, UK.
³ Department of Biochemistry, Liverpool Clinical Laboratories, Liverpool University Hospitals National Health Service Foundation Trust, Liverpool, UK.
⁴ Department of Molecular and Clinical Cancer Medicine, Institute of Systems, Molecular & Integrative Biology, The University of Liverpool, Liverpool, UK.

PMID: 39516252
DOI: 10.1038/s44276-024-00082-6

Abstract

Background: Blood-based biomarkers might help lung cancer diagnosis. A panel of serum tumour markers (TM) has been validated for hospital referrals due to clinical suspicion of lung cancer. We have compared plasma from a cohort enriched for early-stage lung cancer, including controls from a healthy population cohort.

Methods: TM assays for CEA, CYFRA 21-1, CA15.3, ProGRP and SCC were run on a Roche Elecsys 2010 Immunoassay Analyser for a retrospective, nested case-control cohort from the Liverpool Lung Project. The primary endpoints were the sensitivity and specificity of a pre-defined TM panel using published thresholds.

Results: Except for ProGRP, TM levels were significantly higher in cases and ROC AUC values demonstrated significant discriminant power. Accuracy and levels were higher for late-stage cancers, except for ProGRP which was highest in stage 1 cancers. Although providing similar sensitivity (82.4% vs 88.5%), TMs performed worse for specificity (39.3% vs 82%) and overall (Youden's Index 0.22 vs 0.77) and this was not improved by threshold optimisation or binary logistic regression.

Conclusions: Although the TMs were associated with lung cancer status and discriminatory with a high sensitivity when combined, performance was compromised in early-stage disease, which casts some doubt on utility in the screening setting.