Risk prediction models versus simplified selection criteria to determine eligibility for lung cancer screening: an analysis of German federal-wide survey and incidence data

Abstract

As randomized trials in the USA and Europe have convincingly demonstrated efficacy of lung cancer screening by computed tomography (CT), European countries are discussing the introduction of screening programs. To maintain acceptable cost-benefit and clinical benefit-to-harm ratios, screening should be offered to individuals at sufficiently elevated risk of having lung cancer. Using federal-wide survey and lung cancer incidence data (2008–2013), we examined the performance of four well-established risk models from the USA (PLCOM2012, LCRAT, Bach) and the UK (LLP2008) in the German population, comparing with standard eligibility criteria based on age limits, minimal pack years of smoking (or combination of total duration with average intensity) and maximum years since smoking cessation. The eligibility criterion recommended by the United States Preventive Services Taskforce (USPSTF) would select about 3.2 million individuals, a group equal in size to the upper fifth of ever smokers age 50–79 at highest risk, and to 11% of all adults aged 50–79. According to PLCOM2012, the model showing best concordance between numbers of lung cancer cases predicted and reported in registries, persons with 5-year risk ≥ 1.7% included about half of all lung cancer incidence in the full German population. Compared to eligibility criteria (e.g. USPSTF), risk models elected individuals in higher age groups, including ex-smokers with longer average quitting times. Further studies should address how in Germany these shifts may affect expected benefits of CT screening in terms of life-years gained versus the potential harm of age-specific increasing risk of over-diagnosis.

Implementation of lung cancer screening: what are the main issues?

“…Thereby, it is good to realise that risk-based strategies are more likely to recruit older individuals and other groups with diminished life-expectancies (34,38). More research is needed to identify the optimal thresholds for risk-based selection of lung cancer screening eligibles.…”

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

“…To minimally offset the lifetime risk of radiation-induced cancer of about 0.03-0.07 %, as estimated for 50-54 year old men and women in Germany [20], screening participants should have a 5-year lung cancer risk of about 0.5 % or higher if one assumes at least 80 % sensitivity of lung cancer detection and 20 % mortality risk reduction by LDCT screening. Theoretical calculations [58] and analyses of population survey data [52,59] show that NELSON, NLST, or USPSTF criteria may include a proportion of individuals (e. g. younger ages, who quit smoking more than 10 years ago) for whom the ratio of lung cancer deaths to radiation-induced risks and harms related to biopsy or surgery of benign lesions will be less favorable, and who should not be included in screening (see also ▶ Fig. 2).…”

“…The latter approach also provides a better guarantee that each eligible subject will have a minimal individual lung cancer risk required to optimally offset the harms that may result from radiation of invasive investigations triggered by false-positive screening tests. On the other hand, risk-based selection tends to elect individuals in higher age groups [29,52,[60][61][62] who have a higher risk of overdiagnosis. Comparative modeling shows [54] that, for equal numbers of individuals screened, risk-based strategies may avert more lung cancer deaths than current USPSTF recommendations, but with only modestly higher LYG and with considerably more overdiagnosis.…”

“…In Germany, analyses of survey data show that about 3.0 million men and women would be eligible according to NLST criteria, and 3.2 million according to the extended USPSTF criteria. Based on risk prediction models (see below), it can be further estimated that about 40 % or 45 % of yearly incident lung cancer cases would occur in these two risk sets [52]. Using the criteria of the NELSON trial, which require a more moderate smoking history of ≥ 10 cigarettes a day for 30 years or ≥ 15 cigarettes a day for 25 years but more stringent criteria for maximum time since smoking cessation (< 10 years) and cover an overall younger age range of 50 to 75 years, 5.5 million German ever smokers would be eligible, among whom about 47 % of incident lung cancer cases occur [52].…”

Validation of multivariable lung cancer risk prediction models for the personalized assignment of optimal screening frequency: a retrospective analysis of data from the German Lung Cancer Screening Intervention Trial (LUSI)

“…Expert organizations in North America (7,8) and Europe (9) recommend annual screening, with eligibility criteria similar to those used previously in the US National Lung Cancer Screening Trial (NLST) (10), i.e., based on lower and upper limits for age, minimum lifetime cumulative smoking exposure (pack-years) and, for ex-smokers, maximum time since quitting. Compared to the latter eligibility criteria, using more detailed models for the prediction of individuals' LC risk may further improve net benefit and cost-efficiency of LC screening (11)(12)(13)(14).…”