Biomarkers in lung cancer screening: the importance of study design

Low radiation dose computed tomography is an effective method of screening people at high risk of developing lung cancer. Participants are selected either by age and tobacco smoking criteria or multivariable models. Using biomarkers to select people for lung cancer screening may be able to identify those at high risk who do not meet conventional criteria while avoiding further investigation in those without malignant disease. In this issue of the ERJ two biomarkers intended for use in selecting people for CT screening are reported. Both studies are unable to conclude that the biomarker is suitable for this intended use because of issues with the study design. The EarlyCDT-Lung blood test was used to select people at high risk of lung cancer for a regime of LDCT screening but only those with positive tests (10%) had LDCT, which is itself highly sensitive for early-stage lung cancer and can detect cancers 4-6 years before they present. Thus, it is impossible to calculate the contribution of the blood test to the detection of early-stage disease because 90% of the participants were excluded from LDCT. Gaga and colleagues report on the development and validation of a new blood biomarker, Lung EpiCheck; however here the issue is that the case and control groups are different and hence discrimination is likely overestimated. Study design should allow the added contribution of the biomarker to be identified and quantified, in direct comparison to the gold-standard method and in the population in which it is to be used.