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

Abstract

BackgroundBlood-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.MethodsTM 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.ResultsExcept 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.ConclusionsAlthough 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.