Protocol for an Umbrella Review of Non-Invasive Biomarkers used to Guide Pre-diagnostic Decision Making in Lung Cancer Screening (The BIOLUX-Umbrella Study)

<ns3:p>Lung cancer remains a leading cause of mortality worldwide, largely due to diagnosis at an advanced stage. While low-dose computed tomography (LDCT) screening can reduce lung cancer mortality, it carries limitations such as high false-positive rates and radiation exposure. These drawbacks highlight the need for more refined screening approaches. Non-invasive biomarkers have been proposed as tools to improve risk stratification before LDCT. This umbrella review will synthesise existing systematic reviews that evaluate the use of biomarkers in guiding pre-diagnostic decision-making for lung cancer screening. A comprehensive search will be conducted across MEDLINE, Embase, Web of Science, Scopus, and the Cochrane Database of Systematic Reviews. Eligible reviews must focus on individuals enrolled in screening before a lung cancer diagnosis and report on biomarker-based risk stratification. Outcomes of interest include lung cancer incidence and diagnostic accuracy metrics. For each included review, we will extract details on study setting, population, quality assessment methods, biomarker characteristics, and key findings, including sensitivity, specificity, and predictive values where available. The results will be summarised to assess the consistency of findings and identify research gaps. This review will provide a comprehensive overview of current evidence on biomarker use in lung cancer screening. It aims to inform future research and support more efficient, accurate, and less harmful screening strategies.</ns3:p>