A retrospective cohort study found that while never-smokers with non–small cell lung cancer were more likely to present with stage IV disease compared with smokers, they demonstrated significantly better long-term survival rates, living an average of 2.7 years longer.
In the study, published in BMC Medicine, investigators analyzed 155 patients with non–small cell lung cancer (NSCLC) (88 smokers and 67 never-smokers) between 2010 and 2022. They revealed that never-smokers had a median survival of 6.6 years compared with 3.9 years for smokers (P = .045). Additionally, there was no statistically significant difference in 1-year all-cause mortality (P = .90) or 12-month progression-free survival outcomes (P = .28). However, smokers had nearly double the risk of all-cause mortality at 5 years (hazard ratio [HR] = 1.73, P = .056) and 10 years (HR = 1.77, P = .02).
Clinical characteristics showed that smokers were older (69 vs 62 years, P < .001) and more often male (58% male, P = .002). Seventeen percent of smokers were current smokers at the time of diagnosis, and the median pack-years of smoking was 35. The leading cause of mortality in both groups was NSCLC (79.3% for never-smokers and 79.5% for smokers).
Histopathology findings indicated that subsolid and ground-glass nodules were exclusively adenocarcinoma. Adenocarcinoma was more common among never-smokers (77.9%), whereas smokers had a near-even split between adenocarcinoma (48%) and squamous cell carcinoma (43%). Radiology findings showed similar nodule morphology between the groups, with solid nodules being the most common (91.6%).
Never-smokers were more often diagnosed with tumors in the right lower lobe, while smokers more commonly presented with tumors in the right upper lobe. Despite similar nodule characteristics, never-smokers were more frequently diagnosed with stage IV disease (P = .046), positive nodal disease (P = .002), and metastatic disease (P = .004).
The study highlighted potential implications for screening protocols, noting that while low-dose computed tomography screening exists for smokers, "no such screening program exists for never-smokers, which might explain why most never-smoker patients in our study were diagnosed at stage IIIa or higher," the study authors indicated.
The investigators emphasized that understanding these differences could help develop targeted management strategies: "Understanding and correlating clinical and imaging features of NSCLC in never-smokers may help develop artificial intelligence algorithms for improved patient management and prognosis."
Limitations of the study included its retrospective nature and lack of data regarding potential radon and secondhand smoke exposure, which are known risk factors for never-smokers. Additionally, treatment regimens were not evaluated as part of the study protocol.
The authors declared no competing interests.
