Former smokers who previously met lung cancer screening criteria but quit more than 10 years earlier continued to have elevated lung cancer and other-cause mortality, raising questions about whether current cessation-based cutoffs for screening eligibility are appropriate, according to a longitudinal cohort study.
The findings do not establish that screening should be extended, but they suggest that using years since quitting alone to stop eligibility may not fully reflect patients’ risk profiles, researchers reported in BMC Medicine.
The analysis included 24,715 participants in the European Prospective Investigation into Cancer and Nutrition–Heidelberg cohort. Smoking behavior was assessed repeatedly from 1994 through 2014, with mortality follow-up through May 2019. Over that period, 2,974 deaths occurred, including 273 from lung cancer and 2,701 from other causes.
Researchers used time-varying Cox models to estimate mortality by smoking status and by eligibility under German lung cancer screening criteria, which apply to patients aged 50 to 75 years with at least 25 years of smoking, at least 15 pack-years, and fewer than 10 years since quitting. Germany authorized low-dose computed tomography screening for lung cancer in 2024, making questions about eligibility thresholds particularly relevant.
Persistent Risk After Long-Term Quitting
Compared with never smokers, current smokers had approximately twofold to threefold higher hazards of death from causes other than lung cancer, depending on age and sex. Former smokers had lower mortality than current smokers, but risk varied substantially by age at cessation.
Patients who quit early in life had little or no excess other-cause mortality compared with never smokers. This threshold differed by sex, with no statistically significant increase observed among men who quit before age 30 years and women who quit before age 40 years. At later quitting ages, risk increased progressively, reaching nearly twofold in men who quit at age 60 years or older and about 1.5-fold in women who quit at age 50 to younger than 60 years.
Among patients who had once met screening criteria but became ineligible after more than 10 years of cessation, other-cause mortality hazards remained elevated. In men, these ranged from about 1.5-fold to threefold compared with never smokers, and in women from about 1.3-fold to nearly twofold, depending on age.
Notably, absolute rates of other-cause mortality in this “past-eligible” group were similar to those in younger patients who remained eligible for screening. Among men, rates were 33.9 per 1,000 person-years in past-eligible smokers aged 75 to younger than 80 years compared with 27.7 per 1,000 person-years in current-eligible smokers aged 70 to younger than 75 years. Among women, the corresponding rates were 22.9 and 22.4 per 1,000 person-years, although estimates in this subgroup were based on relatively few events (10 deaths over 437 person-years), limiting precision.
Lung Cancer Risk Does Not Decline with Time Since Quitting
For lung cancer outcomes, both current and former smoking were associated with persistently elevated mortality compared with never smoking. Importantly, longer time since cessation was not associated with reduced lung cancer mortality after accounting for cumulative smoking exposure.
A similar pattern was observed for lung cancer incidence, suggesting that the biological risk of lung cancer may remain elevated even after prolonged cessation once substantial cumulative exposure has occurred.
Implications for Screening Eligibility
Taken together, the findings highlight a key tension in screening eligibility: while cessation reduces competing mortality risk, former smokers who previously met eligibility criteria may still retain sufficient lung cancer risk—and comparable overall mortality profiles—to remain candidates for screening consideration, though whether this translates to net clinical benefit remains unestablished.
“The risk of other-cause mortality remains elevated, but less so than for continuing smokers, which may argue for a moderate extension of the maximum age limit for [lung cancer] screening,” wrote Yue Chen, of the German Cancer Research Center, and colleagues.
Limitations
The study was observational and did not evaluate clinical screening outcomes, including benefits of low-dose computed tomography, overdiagnosis, or cost-effectiveness. Screening eligibility was modeled rather than observed in a real-world screening program.
In addition, Cox models were not adjusted for factors beyond age, sex stratification, and smoking-related variables, leaving potential confounding from comorbidities, socioeconomic factors, or other lifestyle variables. Several subgroup estimates—particularly among older women—were based on small numbers of events, limiting precision. The cohort also had lower smoking prevalence than the general German population, which may affect generalizability.
Bottom Line
The findings suggest that fixed cessation-based cutoffs may not fully capture long-term lung cancer risk or competing mortality in former smokers who previously met screening criteria. However, the researchers emphasized that larger studies are needed to determine whether modifying screening stop ages would improve clinical outcomes.
Disclosures: The researchers reported no competing interests. The study was supported by Projekt DEAL, the Europe against Cancer program, German Cancer Aid, the German Federal Ministry of Education and Research, and the German Center for Lung Research.
Source: BMC Medicine
