Smoking cessation before lung cancer diagnosis significantly reduces excess mortality risk
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Key takeaways:
- Former smokers had a 26% higher mortality risk than those who never smoked.
- Associations between smoking history and OS may vary depending on clinical stage at diagnosis.
Patients with non-small cell lung cancer who had stopped smoking before diagnosis had higher rates of survival after diagnosis, results of a retrospective cohort study showed.
The findings — published in JAMA Network Open — showed the greatest survival benefit among those who had gone the longest without smoking prior to diagnosis.
“The longer the cessation period before diagnosis, the better it is for many disease outcomes, especially for [lung cancer] risk,” David C. Christiani, MD, MPH, MS, Elkan Blout professor of environmental genetics at Harvard T.H. Chan School of Public Health, told Healio.
Background
Previous studies of the impact of smoking on lung cancer survival focused on current vs. former smokers at the point of diagnosis and failed to consider the impact of smoking on survival among those who quit before diagnosis, according to Chrisitiani.
“We already known that ... those who stop smoking at the time of their initial diagnosis and treatment or after have a lower risk for recurrence into a progression,” he said. “We wanted to take an incremental step forward to get more granular detail about prediagnosis smoking and the impact it may have on mortality once people are diagnosed with non-small cell lung cancer.”
Having this type of information won’t change treatment approaches but could help researchers more easily account for variability in response to treatment and more accurately predict a patient’s chances of full or partial recovery, he added.
Methodology
The investigators conducted a retrospective cohort study of patients with NSCLC to determine any association between duration of smoking cessation before diagnosis and OS.
The study sample included 5,594 NSCLC survivors (mean age, 65.6 ± 10.8 years; 53.4% men; 93.3% white) in the Boston Lung Cancer Survival Cohort at Massachusetts General Hospital recruited between 1992 and 2022.
Study participants had detailed smoking history and clinical characteristics prospectively collected at study enrollment and during follow-up.
The study cohort comprised 795 (14.2%) never smokers, 3,308 (59.1%) former smokers, and 1,491 (26.7%) current smokers.
Researchers used hospital clinical and cancer registry data to determine OS after lung cancer diagnosis.
Any association between detailed smoking history and OS after NSCLC diagnosis served as the study’s primary outcome measurement.
Key findings
A total of 3,842 (69.1%) participants died during the study follow-up period, including 1,177 (79.3%) current smokers, 2,191 (66.8%) former smokers and 474 (59.6%) never smokers.
Investigators reported significantly longer median OS of 58.9 months (95% CI, 51.9-67.4) among never smokers compared with former smokers (51.2 months; 95% CI, 47.7-54.6) and current smokers (34 months; 95% CI, 29.1-42.3).
A multivariate Cox regression analysis showed former smokers had a 26% higher mortality risk compared with those who never smoked (HR = 1.26; 95% CI, 1.13-1.4). Current smokers had even higher additional mortality risk (68%) than nonsmokers (HR = 1.68; 95% CI, 1.5-1.89).
A subgroup analysis stratified by clinical stage at diagnosis revealed an association between history of smoking and shorter OS among patients with early-stage disease (former smoker vs. never smoker, HR = 1.37; 95% CI, 1.16-1.63; current smoker vs. never smoker, HR = 1.93; 95% CI, 1.61-2.32) compared with patients who received a diagnosis of stage IIIB to stage IV NSCLC (former smoker vs. never smoker, HR = 1.19; 95% CI, 1.03-1.36; current smoker vs. never smoker, HR = 1.43; 95% CI, 1.23-1.66).
Investigators observed a significant association between doubling of years since smoking cessation and lower mortality risk among former smokers (HR = 0.96; 95% CI, 0.93-0.99).
Clinical implications
Christiani hopes the results will lead to more accurate estimates of additional mortality risk based on a granular look at the timing of smoking cessation among those diagnosed with NSCLC.
His group plans further study to determine any impact of timing of smoking cessation on PFS in the era of novel immunotherapies — which tend to be used for late-stage disease — Christiani added.
“I think trials now need to take into account smoking as more than just a yes-no characterization,” he told Healio. “It’s in the interest of people developing new therapies to find out what proportion of people respond, and now we have another variable to put in the equation that may explain variability in response.”
For more information:
David C. Christiani, MD, MPH, MS, can be reached at Department of Environmental Health, Harvard T.H. Chan School of Public Health, Harvard University, 677 Huntington Ave., Boston, MA 02215; email: dchris@hsph.harvard.edu.
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