Patients With Smoking History Have Elevated Long-Term Lung Cancer Risk Despite Negative Initial Screening: JAMA
China: Researchers have discovered in a new cohort study that smokers with negative baseline low-dose CT (LDCT) scans still showed a significantly increased long-term risk of lung cancer, which became evident only after 2 years. These findings support extending the initial screening interval and adopting personalized long-term monitoring strategies based on smoking history.
A study published in JAMA Network Open by Yin Liu and colleagues provides new insights into how tobacco exposure influences lung cancer risk even after an initially reassuring screening result. The research explored the association between smoking status, cumulative exposure measured in pack-years, and duration of smoking cessation with long-term lung cancer outcomes.
The large prospective cohort study was conducted under the Cancer Screening Program in Urban China and included 30,565 individuals aged 40 to 74 years who had negative baseline LDCT findings between 2013 and 2021. Participants were followed until the end of 2023 to monitor the development of lung cancer. Among them, 15,804 were smokers and 14,761 had never smoked.
The study led to the following findings:
- During over 139,000 person-years of follow-up, 76 lung cancer cases were identified.
- Smokers had a significantly higher lung cancer risk than never smokers (AHR 2.73).
- The increased risk was mainly driven by heavier smoking exposure, particularly ≥20 pack-years.
- Individuals with ≥30 pack-years had more than threefold higher lung cancer risk.
- No significant increase in risk was observed within the first 2 years after screening.
- Lung cancer risk became significantly higher from the third year onward (AHR 2.54).
- A nonlinear dose-response relationship was observed, with risk rising markedly beyond ~20 pack-years.
- Women showed higher susceptibility to lung cancer than men at similar smoking exposure levels.
- Individuals aged ≥50 years had increased risk, especially with heavier smoking histories.
- Smoking cessation for less than 15 years did not significantly reduce lung cancer risk.
These findings suggest that a negative LDCT result does not ensure long-term protection, especially for smokers. The authors highlight the need for risk-based screening strategies that consider smoking intensity, duration, age, and sex. Extending screening intervals while maintaining long-term surveillance may improve early detection.
However, limitations include reliance on self-reported smoking data, potential influence of unmeasured confounders such as environmental exposures, and limited statistical power in some subgroup analyses. The findings may also have limited generalizability beyond similar urban populations.
Overall, the study highlights the importance of continued monitoring and personalized screening approaches in individuals with a history of smoking, even after an initial negative LDCT scan.
Reference:
Liu Y, Guo X, Qie R, et al. Tobacco Smoking and Lung Cancer Risk After Negative Baseline Low-Dose Computed Tomography Findings. JAMA Netw Open. 2026;9(3):e261913. doi:10.1001/jamanetworkopen.2026.1913
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