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

Abstract

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).

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 as an imaging biomarker for effective lung cancer risk stratification; however, volume doubling time can effectively be used as an imaging biomarker to rule out lesions with benign tissue growth.

  • The LDCT lung cancer screening interval should eventually be tailored to the expected mean nodule growth of the targeted population, starting with personalized screening, to improve screening performance (in particular for women).

  • Effective smoking cessation interventions must be integrated within cost-effective lung cancer screening programmes.

  • We propose a framework — the Screening Planning and Implementation RAtionale for Lung cancer (SPIRAL) — to define the scope of future implementation research on lung cancer screening programmes.

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Fig. 1: Screening Planning and Implementation RAtionale for Lung cancer.
Fig. 2: Randomized controlled trials of LDCT-based approaches to lung cancer screening.
Fig. 3: The NELSON-Plus Protocol for LDCT scan-detected lung nodules.
Fig. 4: Cost-effectiveness of LDCT-based lung cancer screening.

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M.O. contributed to all aspects of the preparation of this article. S.L. and J.E.W. researched data. M.A.H. contributed to discussions, researched data and supported the draft of the manuscript. J.K.F. contributed to all aspects of the preparation of this article. The final manuscript was approved by all authors.

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Oudkerk, M., Liu, S., Heuvelmans, M.A. et al. Lung cancer LDCT screening and mortality reduction — evidence, pitfalls and future perspectives. Nat Rev Clin Oncol 18, 135–151 (2021). https://doi.org/10.1038/s41571-020-00432-6

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