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

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.

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.

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.

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.