Clinical characteristics of lung cancer in never-smokers: a multicenter Saudi cohort.

Lung cancer remains a major global health problem. According to the latest GLOBOCAN estimates, it was the most commonly diagnosed cancer worldwide in 2022 and the leading cause of cancer death, accounting for about 2.5 million new cases and 1.8 million deaths. Despite advances in systemic therapy and molecular profiling, prognosis remains closely tied to stage at diagnosis, highlighting the importance of clinically characterizing distinct disease phenotypes. Although tobacco exposure remains the dominant risk factor for lung cancer, individuals who have never smoked are now widely recognized as a distinct clinical and biologic entity rather than simply a smoking-independent subset of the same malignancy. Prior reviews have estimated that 10% to 25% of lung cancers occur in never-smokers, with substantial geographic variations. This subgroup is important enough that, if considered separately, would rank among the more common causes of cancer death. Lung cancer in never-smokers differs from smoking-associated lung cancer in several clinically relevant ways: it is more frequently reported in women, commonly associated with adenocarcinoma histology, and is enriched for actionable oncogenic drivers such as Epidermal growth factor receptor (EGFR) mutations and Anaplastic lymphoma kinase (ALK) rearrangements. These differences have direct implications for diagnosis, molecular testing, and treatment. Data from the Middle East remain comparatively limited. The age-standardized incidence rate of lung cancer in Saudi Arabia in 2022 was 4.4 per 100 000 (1585 cancers in one year) with marked regional variation; lung cancer ranks approximately fifth among cancers in Saudi men and seventeenth in women, reflecting historically low-though rising-tobacco consumption, particularly among women.