Lung cancer is the leading cause of cancer death in the US. While an extensive literature exists detailing lung cancer risk factors and mortality among patients with a history of tobacco use, the data are more limited among individuals who have never smoked. The purpose of this investigation is to compare survival rates between the two groups and evaluate potential risk factors among never smokers.
This retrospective study included 3380 smokers and 334 never smokers who were diagnosed with lung cancer at Stony Brook University Hospital between 2003 and 2016. 1-, 3-, 5- and 10-year survival outcomes, stratified by smoking status, were compared and Kaplan-Meier curves for overall survival are provided. Cox Proportional Hazard models were used to evaluate factors influencing survival among never smokers.
Never smokers with lung cancer were more likely to be female, be diagnosed with adenocarcinoma histology, and had fewer comorbidities than lung cancer patients who smoked. Although 60% of patients were diagnosed at a later stage of disease development, regardless of smoking status, overall short- and long-term survival was significantly higher among never smokers compared to those with a history of tobacco use. In addition to age and stage at diagnosis, a history of diabetes was found to be a significant prognostic factor for decreased survival among never smokers (HR=3.15, 95% CI (1.74, 5.71)).
Data from the present investigation suggest that, regardless of smoking status, approximately three of every five lung cancer patients are diagnosed at a later stage, and that both short- and long-term survival outcomes are significantly better among never smokers compared to those with a history of tobacco use. Additional studies are required to validate these findings and better explain the mechanistic drivers for the improved outcomes among never smokers.
Sixty percent of patients with lung cancer were diagnosed at stage III/IV, regardless of smoking status.
Short- and long-term survival rates were significantly higher among never smokers compared to smokers.
Older age, later stage of diagnosis and a history of diabetes were found to significantly decrease survival among never smokers.
Lung cancer mortality leads all other cancer types with a 5-year survival rate of 19% . While tobacco use is the most significant risk factor for the development of lung cancer, 10–30% of cases involve patients who have never smoked . Recent studies have suggested that the etiology of lung cancer in smokers may be different than in abstainers . Never-smoker lung cancer patients are reported as more likely to be female, to be of older age, and to have higher socioeconomic status. Additionally, they typically have fewer co-morbidities and an adenocarcinoma diagnosis .
Radon has been cited by the United States Environmental Protection Agency (USEPA) and World Health Organization (WHO) as a leading cause of lung cancer among never smokers ( and it has recently been reported that indoor radon exposure may have a negative effect on survival . A number of review articles and meta- analyses have further implicated other risk factors for lung cancer among never smokers. These include (but are not limited to) a variety of genetic determinants , inhalation of second hand smoke and some infections (e.g., tuberculosis and human papilloma virus) and inflammatory diseases (e.g., asthma and sarcoidosis) . Additionally, a pooled analysis of 6 multi-center case-control studies reported that wine and spirits may increase lung cancer risk among never smokers, particularly in women . It remains unclear, however, to what extent these factors impact disease development and mortality.
There have been conflicting reports in the literature regarding survival outcomes in never smokers compared to those with a history of tobacco use. Some studies have reported a survival benefit among never smokers , while others found no difference in rates between the two groups . Furthermore, there is a scarcity of longitudinal data describing survival outcomes among never smokers and the majority of reports provide rates up to and including 5-years with few, if any, comparing outcomes for a longer term. The purpose of this investigation was to compare 1-, 3-, 5- and 10-year survival outcomes between smokers and never smokers and to identify predictors of mortality among the latter group.