Lung cancer in never smokers: from early detection to prevention

Lung cancer in never smokers (LCINS) is a growing global health challenge. Unlike smoking-related lung cancer, LCINS is characterized by distinct epidemiological patterns and unique molecular pathogenesis and, consequently, requires different clinical management approaches. Unfortunately, for patients with lung cancer who have never smoked, symptoms are nonspecific and often dismissed due to these patients not fitting a high-risk profile (e.g., smoker), underscoring the need for improved detection and interception. Emerging risk factors, including germline variants, clonal hematopoiesis, and environmental exposures, offer new avenues for risk stratification and preventive strategies. While low-dose computed tomography screening shows promise in high-risk subgroups, challenges remain in optimizing cost-effectiveness. Novel prevention approaches, from interleukin (IL)-1β inhibition to cancer vaccines, are under investigation. This opinion article discusses why LCINS demands unique clinical and research paradigms to address its biological complexity.