Lung cancer across borders: From molecular epidemiology to precision treatment strategies

Lung cancer remains the leading cause of cancer-related mortality worldwide, accounting for approximately 1.8 million deaths annually. Beyond this universal burden, lung cancer is profoundly heterogeneous, shaped by geography, environmental exposures, genetic ancestry, and unequal access to molecular diagnostics and modern therapies. Compelling evidence indicates that non-small cell lung cancer (NSCLC) is not a single entity but a constellation of molecularly distinct subtypes whose distribution reflects regional carcinogens and population-specific susceptibilities. This Special Collection of Therapeutic Advances in Medical Oncology assembles five complementary studies that address the geographical heterogeneity of NSCLC. A comprehensive review by Laguna and colleagues maps the worldwide distribution of risk factors and molecular subtypes, illustrating how tobacco, indoor radon, air pollution, arsenic, biomass smoke, and genetic ancestry converge to produce distinct molecular landscapes across continents. García-Pardo and colleagues extend this framework with the RADON EUROPE study, the first ecological analysis to link estimated indoor radon exposure with ALK fusion prevalence across 21 European countries. Marjanski and colleagues expose critical gaps in real-world perioperative assessment in Poland, where limited preoperative biomarker testing and prolonged surgical intervals may exclude patients from neoadjuvant chemoimmunotherapy. Mo and colleagues describe an emerging consequence of therapeutic progress: a temporal rise in cardiovascular and pulmonary diseasespecific mortality in NSCLC, coinciding with the expanded use of targeted therapies and immune checkpoint inhibitors. Pham and colleagues demonstrate, in a Vietnamese cohort with EGFR-mutant NSCLC, that flexible, individualized afatinib dosing improves outcomes and underscores the persistent underrepresentation of non-European populations in pivotal trials. Taken together, these articles illustrate that the geographic distribution of carcinogens shapes molecular subtypes; molecular subtypes dictate treatment options; treatment options generate toxicities that must be managed within local healthcare systems; and those systems, in turn, determine equitable access to diagnostic and therapeutic innovation. Bridging these gaps will require integration of exposome-informed approaches, more diverse clinical trial populations, cardio-oncology surveillance, and pharmacological individualization. This editorial advocates for a geographically informed and globally equitable approach to thoracic oncology.