Lung Cancer Screening by Low-Dose Computed Tomography – Part 1: Expected Benefits, Possible Harms, and Criteria for Eligibility and Population Targeting

Abstract

Background Trials in the USA and Europe have convincingly demonstrated the efficacy of screening by low-dose computed tomography (LDCT) as a means to lower lung cancer mortality, but also document potential harms related to radiation, psychosocial stress, and invasive examinations triggered by false-positive screening tests and overdiagnosis. To ensure that benefits (lung cancer deaths averted; life years gained) outweigh the risk of harm, lung cancer screening should be targeted exclusively to individuals who have an elevated risk of lung cancer, plus sufficient residual life expectancy. Methods and Conclusions Overall, randomized screening trials show an approximate 20 % reduction in lung cancer mortality by LDCT screening. In view of declining residual life expectancy, especially among continuing long-term smokers, risk of being over-diagnosed is likely to increase rapidly above the age of 75. In contrast, before age 50, the incidence of LC may be generally too low for screening to provide a positive balance of benefits to harms and financial costs. Concise criteria as used in the NLST or NELSON trials may provide a basic guideline for screening eligibility. An alternative would be the use of risk prediction models based on smoking history, sex, and age as a continuous risk factor. Compared to concise criteria, such models have been found to identify a 10 % to 20 % larger number of LC patients for an equivalent number of individuals to be screened, and additionally may help provide security that screening participants will all have a high-enough LC risk to balance out harm potentially caused by radiation or false-positive screening tests. Key Points: Citation Format

Design and Rationale of the HANSE Study: A Holistic German Lung Cancer Screening Trial Using Low-Dose Computed Tomography

“…In addition, there is the risk of lung cancer overdiagnosis with increasing age and comorbidities 10 . The PLCO M2012 risk score is known to select participants that are slightly older with more comorbidities compared to the inclusion criteria based on age and smoking history 23 .…”

“…LCS should be targeted at individuals with a high risk of developing lung cancer, such that the expected benefits (mortality reduction) outweigh the risks of adverse effects, notably false-positive diagnoses and overdiagnosis, in comparison to financial costs 10 11 . Traditionally, the target population has been defined by concise criteria including age and lifetime cumulative smoking history 4 6 .…”

Lung Cancer Screening by Low-Dose Computed Tomography: Part 2 – Key Elements for Programmatic Implementation of Lung Cancer Screening

“…As discussed in the first part of our review [10], in view of the potential harms of overdiagnosis, screening should be offered only to individuals with sufficiently high residual life expectancy. At the same time, their risk of having lung cancer should be sufficiently high for the expected screening benefit (life years gained) to outweigh risks related to radiation exposure and invasive medical investigations triggered by false-positive screening tests.…”

“…With the maximum age of screening eligibility set at 74 years (i. e., stopping age of 75), the criteria such as those used in NLST (corresponding to about 3.0 million eligible ever-smokers in Germany, and covering about 38 % of all incident lung cancer cases) or NELSON (about 5.5 million eligible, covering about 46 % of incident cases) can be used, where the overall breadth of inclusion criteria may further depend on cost-efficiency and acceptance by health insurances [15]. Within broadly defined criteria, such as those of NELSON or NLST, the complementary use of more precise risk models based on age, sex, and lifetime smoking history [16][17][18][19] may further help ensure that each single screening participant will have a sufficiently elevated LC risk to anticipate positive net benefit from screening [10].…”

“…Part 1 of this review [10] reports on the epidemiologic backgrounds of lung cancer screening, the effects on lung cancer mortality in recent screening trials, the potential harms of screening, and how to identify persons who may benefit from taking part. In this second part, based on experiences and lessons learned from the German Lung Cancer Screening Intervention trial (LUSI) [8,11] as well as other screening trials in Europe and North America, we outline a number of organizational requirements for the successful programmatic implementation of high-quality cancer screening on a local level, including organized invitations and eligibility checks, systematic and quality-controlled performance of screening tests, and optimized oncologic treatment and structures for quality monitoring.…”