Newly published research in JAMA Network Open suggests that changes may be necessary for low-dose computed tomography (LDCT) screening protocols in people deemed to be at high risk for lung cancer.
For the prospective study, researchers examined potential association between smoking status, pack-year history and time since cessation of smoking in 30,565 participants who had negative findings on baseline LDCT exams. The cohort was comprised of 14,761 never smokers and 15,804 smokers, according to the study.
The study authors found that smokers in this cohort with negative baseline LDCTs were over 2.7 times more likely than never smokers to develop lung cancer.
However, the researchers also determined there was no significantly elevated risk at two years with smokers and no significant association between reduced lung cancer risk and short-term cessation of smoking (< 15 years).
“These findings challenge current screening paradigms and provide actionable evidence for refining LDCT guidelines and tobacco control strategies,” noted lead study author Yin Liu, Ph.D., who is affiliated with the Department of Cancer Epidemiology at the Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital in Zhengzhou, China, and colleagues.
In contrast to never smokers, the researchers noted a nearly 2.5 times higher risk of lung cancer among those with 20 < 30 pack years and over a three times higher risk for people with > 30 pack years.
However, the study authors also determined that women with > 30 pack years had a greater than fourfold higher risk for lung cancer than men with similar pack years (5.78 adjusted hazard ratio (AHR) vs. 1.36 AHR).
Three Key Takeaways
• Persistent elevated risk despite negative baseline LDCT. Smokers with initially negative LDCT scans remained at significantly higher risk (≈2.7×) of developing lung cancer compared to never smokers, underscoring that a negative baseline scan does not equate to low future risk in this population.
• Pack-year burden and sex differences matter. Lung cancer risk increased with cumulative smoking exposure (> three times risk for >30 pack-years), with notably higher relative risk observed in women than men at similar exposure levels, highlighting the potential need for sex-specific risk stratification.
• Limited short-term risk reduction with recent cessation. No significant reduction in lung cancer risk was observed within two years or with short-term smoking cessation (<15 years), suggesting current screening intervals and eligibility criteria may need refinement to better reflect ongoing risk in former smokers.
While cautioning that this difference may be inflated due to one lung cancer occurring in the male never smoker cohort, the researchers maintained that prior research has shown similar findings.
“As smoking rates among women in low- and middle-income countries continue to rise, these findings underscore the need for mechanistic research into sex differences in lung carcinogenesis and support the development of sex-specific screening and cessation programs,” posited Liu and colleagues.
(Editor’s note: For related content, see “Chest CT Research Reveals at Least One Lung Nodule in 42 Percent of Non-Smokers,” “Can AI Predict Future Lung Cancer Risk from a Single CT Scan?” and “CT-Based Deep Learning Model May Reduce False Positives with Indeterminate Lung Nodules by Nearly 40 Percent.”)
In regard to study limitations, the authors conceded that the urban Chinese cohort may limit extrapolation of the findings to broader patient population and those in non-urban settings. The researchers also suggested that unmeasured cofounding factors, such as genetic factors and air pollution, could have impacted risk estimates. They also acknowledged that smoking history and cessation status were self-reported.
