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Original Investigation
July 28, 2022

Assessment of Lung Cancer Risk Among Smokers for Whom Annual Screening Is Not Recommended

Author Affiliations
  • 1Veterans Affairs Medical Center, Washington, DC
  • 2Department of Medicine, School of Medicine, George Washington University, Washington, DC
  • 3Department of Medicine, School of Medicine, Uniformed Services University, Washington, DC
  • 4Department of Biostatistics, School of Public Health, University of Alabama at Birmingham, Birmingham
  • 5Department of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham
  • 6Department of Medicine, School of Medicine, University of California, Los Angeles, Los Angeles
  • 7Department of Surgery, School of Medicine, George Washington University, Washington, DC
  • 8Department of Biomedical Engineering, School of Engineering and Applied Science, George Washington University, Washington, DC
  • 9Department of Medicine, School of Medicine, University of Alabama at Birmingham, Birmingham
  • 10Department of Medicine, School of Medicine, University of California, San Francisco, San Francisco
  • 11Department of Medicine, School of Medicine, Yale University, New Haven, Connecticut
  • 12Department of Medicine, School of Medicine, Georgetown University, Washington, DC
JAMA Oncol. Published online July 28, 2022. doi:10.1001/jamaoncol.2022.2952
Key Points

Question  What is the risk of lung cancer among smokers for whom annual low-dose computed tomography screening is not recommended?

Findings  In this cohort study of 4279 individuals 65 years and older who were followed up for a median (IQR) of 13.3 (7.9-18.8) years, former smokers with a 20 pack-year or greater smoking history who quit 15 or more years before baseline and current smokers with less than 20 pack-years of smoking (2 groups not recommended for lung cancer screening) had a 10-fold greater risk of lung cancer than never smokers.

Meaning  These findings suggest that there is a need to develop and test prediction models to identify high-risk subsets of these smokers for lung cancer screening and highlight the importance of abstinence and early cessation.

Abstract

Importance  The US Preventive Services Task Force does not recommend annual lung cancer screening with low-dose computed tomography (LDCT) for adults aged 50 to 80 years who are former smokers with 20 or more pack-years of smoking who quit 15 or more years ago or current smokers with less than 20 pack-years of smoking.

Objective  To determine the risk of lung cancer in older smokers for whom LDCT screening is not recommended.

Design, Settings, and Participants  This cohort study used the Cardiovascular Health Study (CHS) data sets obtained from the National Heart, Lung and Blood Institute, which also sponsored the study. The CHS enrolled 5888 community-dwelling individuals aged 65 years and older in the US from June 1989 to June 1993 and collected extensive baseline data on smoking history. The current analysis was restricted to 4279 individuals free of cancer who had baseline data on pack-year smoking history and duration of smoking cessation. The current analysis was conducted from January 7, 2022, to May 25, 2022.

Exposures  Current and prior tobacco use.

Main Outcomes and Measures  Incident lung cancer during a median (IQR) of 13.3 (7.9-18.8) years of follow-up (range, 0 to 22.6) through December 31, 2011. A Fine-Gray subdistribution hazard model was used to estimate incidence of lung cancer in the presence of competing risk of death. Cox cause-specific hazard regression models were used to estimate hazard ratios (HRs) and 95% CIs for incident lung cancer.

Results  There were 4279 CHS participants (mean [SD] age, 72.8 [5.6] years; 2450 [57.3%] women; 663 [15.5%] African American, 3585 [83.8%] White, and 31 [0.7%] of other race or ethnicity) included in the current analysis. Among the 861 nonheavy smokers (<20 pack-years), the median (IQR) pack-year smoking history was 7.6 (3.3-13.5) pack-years for the 615 former smokers with 15 or more years of smoking cessation, 10.0 (5.3-14.9) pack-years for the 146 former smokers with less than 15 years of smoking cessation, and 11.4 (7.3-14.4) pack-years for the 100 current smokers. Among the 1445 heavy smokers (20 or more pack-years), the median (IQR) pack-year smoking history was 34.8 (26.3-48.0) pack-years for the 516 former smokers with 15 or more years of smoking cessation, 48.0 (35.0-70.0) pack-years for the 497 former smokers with less than 15 years of smoking cessation, and 48.8 (31.6-57.0) pack-years for the 432 current smokers. Incident lung cancer occurred in 10 of 1973 never smokers (0.5%), 5 of 100 current smokers with less than 20 pack-years of smoking (5.0%), and 26 of 516 former smokers with 20 or more pack-years of smoking with 15 or more years of smoking cessation (5.0%). Compared with never smokers, cause-specific HRs for incident lung cancer in the 2 groups for whom LDCT is not recommended were 10.54 (95% CI, 3.60-30.83) for the current nonheavy smokers and 11.19 (95% CI, 5.40-23.21) for the former smokers with 15 or more years of smoking cessation; age, sex, and race–adjusted HRs were 10.06 (95% CI, 3.41-29.70) for the current nonheavy smokers and 10.22 (4.86-21.50) for the former smokers with 15 or more years of smoking cessation compared with never smokers.

Conclusions and Relevance  The findings of this cohort study suggest that there is a high risk of lung cancer among smokers for whom LDCT screening is not recommended, suggesting that prediction models are needed to identify high-risk subsets of these smokers for screening.

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    2 Comments for this article
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    Exposure intensity, cumulative effect and smoking cessation
    Saeed Taheri, M.D. | NLMJ; Lahijan
    An incredible study providing such a robust & extensive data on a hottest topic for the first time to the literature; here I want to raise some points. In the interpretation of the study results we should consider that although the cancer incidence curves start at point zero for all, that doesn't mean that's indicative of a universal starting point for the different study groups. For example, for nonheavy (NH) smokers with cessation duration >15 years, point zero is indicative of about 15 years after smoking cessation. & considering the overall curves presented in the figure for either the current or former smokers, the steep of event rates seem to be attenuated by time, with higher event rates within the earlier time periods relative to the smoking start time. This mean that although the curves associated with smoking cessation populations are lower than the current smokers, that might be due to the longer time period that had been lapsed after the exposure start point, and now their curves reaching some state of plateau.
    Another significant finding of the current study is the effects of smoking intensity on the incident lung cancers. There are two evidence presented in this study that the intensity of smoking is as important as the cessation, if not even more, in the prediction of cancer incidence. Unexpectedly, former NH (<20PY) smokers who ceased smoking >15 years have a cancer incidence curve of a little above the counterparts who have ceased smoking for <15 years. But if you see their detailed data, despite having an overall lower pack/years of smoking (8.4 vs. 10.1), the former group had a relatively higher number of cigarettes smoked per day (10 vs 5) compared to the groups with <15 years smoking cessation. This might indicate that the intensity of smoking (indicated by cigarettes/day) is an overwhelming factor in predicting lung cancers. The almost overlapping cancer incidence curves for the current <20PY smokers & former >20PY smokers quitting >15 years also confirms the relative importance of smoking intensity (as well as pack/years) besides the cessation effect.
    One explanation for this observation could be the long-term effects of smoking on epimutation (alterations in epigenetic signature) that are supposed to be relatively persistent despite smoking cessation. Of course the abovementioned discussions are not arguing against the beneficial effects of smoking cessation in the incidence of lung cancers, but I just tried to bring more factors into the equation for adjustments.
    CONFLICT OF INTEREST: None Reported
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    Isn't there an error in the abstract?
    Philip Kleine, Dr. med. | Wuerzburg University Hospital
    The last sentence of the"results"reads: "...age, sex, and race–adjusted HRs were 10.06 (95% CI, 3.41-29.70) for the current nonheavy smokers and 10.22 (4.86-21.50) for the former smokers with LESS than 15 years of smoking cessation compared with never smokers." (Bold types by me)

    As the research ist concerned with the risk of those who do not qualify for screening, "for the former smokers with MORE than 15years of smoking cessation" should be correct.
    CONFLICT OF INTEREST: None Reported
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