Benefit-risk assessment of lung cancer screening for (ex-)smokers using low-dose CT

Patient in einem CT-Gerät Source: REB Images via Getty Images

Background

Lung cancer is a serious disease that primarily affects smokers. In Germany, it is the leading cause of cancer deaths in men and the second most common in women. The question is therefore whether screening measures are advisable for this group of people. The World Health Organization (WHO) sees the purpose of tests for early detection as being to identify cancer precursors or early stages of cancer in asymptomatic individuals. Timely diagnosis and the early initiation of treatment can lead to better outcomes for some people (WHO 2022). Thanks to technical progress, low-dose computed tomography (LDCT) in particular provides good conditions for the early detection of lung cancer. At a relatively low radiation dose, it has proven to be sensitive enough to detect even small tumours with a diameter of a few millimetres (Yau et al. 2007).

Objective

In a preliminary investigation, lung cancer screening with LDCT was identified as a promising method. The BfS has investigated whether and in what circumstances the use of this technique for (ex-)smokers outweighs the associated harm and risk due to radiation exposure. The results were intended to provide the Federal Ministry for the Environment, Nature Conservation, Nuclear Safety and Consumer Protection (BMUV) with a basis for decision-making regarding the authorisation of LDCT screening.

Methods

Benefit-risk assessment

The benefit-risk assessment was carried out in several stages. A systematic literature review served to record advantages and disadvantages of LDCT screening that had been identified in clinical studies, including the reduction of lung cancer mortality and possible harm due to false-positive screening results or overdiagnoses. Subsequently, the risk arising due to radiation exposure in regular LDCT examinations was estimated and weighed up against the benefit.

Systematic literature review

For the systematic literature review, a search was made of electronic databases in April 2020. Complete publications of studies were included if they were randomised controlled trials (RCTs) of current or former heavy smokers that compared LDCT screening either with no screening or with screening by means of a chest X-ray. The main focus of the review was on disease-specific mortality. Among the other interesting findings were lung cancer incidence, including information on tumour stage and histology, invasive further diagnostic examinations, false-positive screening results, overdiagnoses and health-related quality of life, including psychosocial consequences and radiation exposure. The studies were reviewed, selected, checked and systematically evaluated by two independent experts from the BfS with a background in epidemiology.

Risk assessment

The radiation risk was assessed using established gender-, age- and organ-specific radiation epidemiological models adapted to a German population of smokers. The assessment incorporated representative organ doses calculated for a volume CT dose index of 1 milligray (mGy), which can be achieved on modern systems. The radiation risks were assessed for various screening scenarios, taking account of the participants’ age and gender.

Summary

Benefit: estimate based on literature review

Based on the systematic literature review, the effect of LDCT lung cancer screening was the subject of a meta-analysis of eight studies (RCTs) with a total of more than 87,000 participants. The relative reduction in lung cancer mortality due to screening with LDCT was 20% in comparison to no screening.

Risk assessment

This benefit must be weighed up against the associated adverse effects on health – and particularly against the radiation risks in the case of LDCT lung screening.

Annual LDCT screening of (ex-)smokers aged between 50 and 75 is estimated to be associated with the following radiation risks of developing cancer within the remaining lifespan: 0.25 % for women and approximately 0.1 % for men. If the determined reduction in lung cancer mortality of approximately 20 % is compared with the radiation risk, this screening scenario has a benefit-risk ratio of approximately 10 avoided lung cancer deaths per additional cancer death for women and approximately 25 per additional death for men.

Further adverse effects can result from overdiagnosis, which is sometimes associated with invasive follow-up examinations. LDCT often leads to false-positive results, identifying conspicuous changes that do not turn out to be lung cancer on further examination. In the studies, particularly following the first LDCT scan, it was common for up to 25 % of people to be summoned for further diagnostic examinations even though lung cancer was only diagnosed in approximately 1 %.

The above estimates of benefit-risk ratio are based on the results of RCTs of the highest evidence level. Stringent quality management for the entire screening process and regular evaluation of the measure are essential so that benefit also outweighs risk in the comprehensive healthcare context.

References:

Hunger, T.;Wanka-Pail, E.; Brix, G.; Griebel, J. Lung Cancer Screening with Low-Dose CT in Smokers: A Systematic Review and Meta-Analysis. Diagnostics 2021, 11, 1040.

Nekolla, E.A.; Brix, G.; Griebel, J. Lung Cancer Screening with Low-Dose CT: Radiation Risk and Benefit–Risk Assessment for Different Screening Scenarios. Diagnostics 2022, 12, 364.