Lung cancer screening necessary for at-risk non-smokers

Never smokers with selected risk factors who undergo lung cancer screening may show similar detection rates to high-risk ever smokers or even higher rates when compared with unselected never smokers, reveals a Singapore study.

“When high-risk never smokers undergo low-dose computed tomography (LDCT) screening, detection rates for incident lung cancer may be several-fold higher than when unselected never smokers undergo screening,” said study author Dr Kay Choong See, senior consultant, Division of Respiratory and Critical Care Medicine, Department of Medicine, National University Hospital, Singapore.

In this study, See searched the database of PubMed from inception through 23 October 2022, with an update on 4 June 2023, for relevant studies.

Thirteen lung cancer screening studies involving unselected never smokers were included. The detection rates in this population ranged from 0.1 percent to 1.1 percent, while the positive predictive values ranged from 0.4 percent to 4.5 percent. [Singapore Med J 2026;67:3-10]

On the other hand, three lung cancer screening studies involved selected never smokers, with selection based primarily on occupational asbestos exposure, environmental radon exposure, and family history of lung cancer in first-degree relatives. The detection rates in this cohort ranged from 0.3 percent to 2.6 percent, while positive predictive values ranged from 0.7 percent to 15 percent.

In addition, 80 percent to 100 percent of lung cancer cases discovered by screening were early stage. However, data indicating survival benefit were limited.

“[C]urrent observational studies support further development of risk model-aided lung cancer screening for never smokers,” See said. “To optimize selection, promising risk factors include occupational asbestos exposure, environmental radon exposure, and family history of lung cancer in first-degree relatives.”

Risk models

Separate risk models with multiple risk factors have been generated using data from screening studies involving unselected never smokers. These models are necessary for never smokers, since existing models such as PLCOm2011 and PLCOm2012 prediction calculators are not suitable for non-smokers, according to See.

“One example is the CanSPUC risk model based on age, male gender, low education attainment, family history of lung cancer, history of tuberculosis, and absence of hyperlipidaemia,” See said.

This model had a moderate predictive discrimination for lung cancer risk, with AUCs of 0.668, 0.678, and 0.685 for 1-, 3-, and 5-year lung cancer risk, respectively. [Front Oncol 2021;11:766939]

“However, risk thresholds that identify high-risk subjects to increase detection rates tend to reduce the number of eligible participants,” See said. “An optimal threshold depends on not only the statistics of screening, but also society’s willingness to pay for screening and the healthcare system’s capacity for screening.”

A high LDCT screening burden may worsen imaging delays for patients with confirmed lung cancer in health systems at risk of overload. [Cancer Epidemiol 2022;79:102156]

“To mitigate screening burden, machine learning methods may be used to analyse clinical parameters and refine candidate selection, such that lower-risk subjects are excluded without affecting the detection of early-stage lung cancer cases,” See said. [Radiology 2022;305:209-218] 

“Further research is currently needed to construct and validate risk stratification models, especially in settings outside of Asia,” See added.