Lung cancer LDCT screening and mortality reduction — evidence, pitfalls and future perspectives

In the past decade, the introduction of molecularly targeted agents and immune-checkpoint inhibitors has led to improved survival outcomes for patients with advanced-stage lung cancer; however, this disease remains the leading cause of cancer-related mortality worldwide. Two large randomized controlled trials of low-dose CT (LDCT)-based lung cancer screening in high-risk populations — the US National Lung Screening Trial (NLST) and NELSON — have provided evidence of a statistically significant mortality reduction in patients. LDCT-based screening programmes for individuals at a high risk of lung cancer have already been implemented in the USA. Furthermore, implementation programmes are currently underway in the UK following the success of the UK Lung Cancer Screening (UKLS) trial, which included the Liverpool Health Lung Project, Manchester Lung Health Check, the Lung Screen Uptake Trial, the West London Lung Cancer Screening pilot and the Yorkshire Lung Screening trial. In this Review, we focus on the current evidence on LDCT-based lung cancer screening and discuss the clinical developments in high-risk populations worldwide; additionally, we address aspects such as cost-effectiveness. We present a framework to define the scope of future implementation research on lung cancer screening programmes referred to as Screening Planning and Implementation RAtionale for Lung cancer (SPIRAL). Despite the introduction of novel therapies, lung cancer remains the leading cause of cancer-related mortality worldwide. Randomized controlled trials of low-dose CT-based lung cancer screening in high-risk populations have shown a reduction in mortality. The authors of this Review discuss these studies and present the Screening Planning and Implementation RAtionale for Lung cancer (SPIRAL), a framework to define the scope of future implementation research on lung cancer screening. Key points The role of CT lung cancer screening on lung cancer-related mortality reduction has been under debate for five decades and is now an evidence-based reality. The implementation of low-dose CT (LDCT)-based screening requires an optimal risk modelling methodology in order to select the high-risk population that will derive the greatest benefits. Biomarkers have the potential to be included in future risk assessment models and work-up of CT nodules; laboratory tests should be developed to improve risk assessment before CT screening. LDCT-based lung nodule diameter measurement cannot be used