Ecological time-series study of lung cancer incidence in relation to tobacco control and harm reduction in the Czech Republic

Lung cancer remains the leading cause of cancer mortality and is largely driven by tobacco smoking. In the Czech Republic, tobacco-control policies and smoking behaviors have changed over the last decade, alongside the introduction of smoke-free nicotine alternatives. We assessed population-level lung cancer incidence trends, emphasizing sex-, age- and histology-specific patterns.We analyzed National Cancer Registry data (01/2010-12/2022) comprising 85,065 incident lung cancer cases in individuals aged ≥15 years. Monthly crude incidence rates (per 100,000) were cleaned, decomposed, outliers detected by the generalized Extreme Studentized Deviate test were replaced, and seasonal components were removed. Segmented (piecewise) linear models were fitted overall and stratified by sex, age group (younger vs older), and histology (small-cell lung cancer [SCLC], non-small cell lung cancer [NSCLC], adenocarcinoma [AC], and squamous cell carcinoma [SQCC]). Changepoints were selected using the Bayesian Information Criterion, and post-changepoint trends were compared with counterfactual projections based on pre-changepoint slopes.Overall incidence was broadly stable, masking divergent sex-specific trends: a steady decline in men and an increase in women. SQCC declined markedly (overall break ~03/2013) and SCLC decreased mainly in men, while women-particularly older women-showed stable-to-increasing SCLC. AC showed the strongest age-by-sex divergence: AC incidence increased persistently in older women, whereas in younger women it peaked around ~07/2015 and then declined/stabilized versus counterfactual growth. This decrease in younger women is very likely related to higher uptake and adherence to smoke-free nicotine alternatives in this cohort, reducing exposure to combustion-derived carcinogens; however, this interpretation is hypothesis-generating given the ecological design.Importantly, AC is thought to arise through both smoking-dependent and smoking-independent carcinogenic pathways (including other inhalational exposures, i.e., non-tobacco smoke); nevertheless, cumulative exposure to cigarette smoke remains a major determinant of AC risk. In conclusion, Czech lung cancer epidemiology shows pronounced sex- and age-specific divergence and an ongoing shift in histologic composition. While patterns are compatible with evolving tobacco exposure and harm-reduction uptake, causal attribution is limited by the ecological design; longer follow-up and linkage with individual-level exposure data are needed.