Screening approaches for lung cancer by blood-based biomarkers: Challenges and opportunities.

Lung cancer (LC) is one of the leading causes for cancer-related deaths in the world, accounting for 28% of all cancer deaths in Europe. Screening for lung cancer can enable earlier detection of LC and reduce lung cancer mortality as was demonstrated in several large image-based screening studies such as the NELSON and the NLST. Based on these studies, screening is recommended in the US and in the UK a targeted lung health check program was initiated. In Europe lung cancer screening (LCS) has not been implemented due to limited data on cost-effectiveness in the different health care systems and questions on for example the selection of high-risk individuals, adherence to screening, management of indeterminate nodules, and risk of overdiagnosis. Liquid biomarkers are considered to have a high potential to address these questions by supporting pre- and post- Low Dose CT (LDCT) risk-assessment thereby improving the overall efficacy of LCS. A wide variety of biomarkers, including cfDNA, miRNA, proteins and inflammatory markers have been studied in the context of LCS. Despite the available data, biomarkers are currently not implemented or evaluated in screening studies or screening programs. As a result, it remains an open question which biomarker will actually improve a LCS program and do this against acceptable costs. In this paper we discuss the current status of different promising biomarkers and the challenges and opportunities of blood-based biomarkers in the context of lung cancer screening.