Inhaled corticosteroid use and the incidence of lung cancer in COPD

Background: Inhaled corticosteroids (ICS) are suggested for potential chemoprevention of lung cancer. Several observational studies in patients with chronic obstructive pulmonary disease (COPD) reported inconsistent results, either significant reductions in lung cancer incidence with ICS use or no effect. We assessed this association, using an approach that avoided biases affecting some of the studies. Methods: A cohort of patients with COPD, new users of long-acting bronchodilators over 2000-2014, was formed using the Quebec healthcare databases, and followed until 2015 for a first diagnosis of lung cancer. A 1-year delay after cohort entry was used to avoid protopathic bias and a 1-year latency period was included after the initiation of ICS use. A time-dependent Cox regression model was used to estimate the hazard ratio (HR) of lung cancer associated with ICS exposure, adjusted for covariates. Results: The cohort involved 63 276 subjects, including 63% receiving ICS, with 3743 lung cancers occurring during a mean follow-up of 5 years. The adjusted HR of lung cancer associated with any ICS exposure was 1.01 (95% CI 0.94-1.08), relative to no ICS use. The HR with longer time (>4 years) since ICS initiation was 0.92 (95% CI 0.83-1.03), while with higher mean daily ICS dose (>1000 mu g fluticasone equivalents) was 1.36 (95% CI 1.03-1.81). Conclusions: Inhaled corticosteroid use is not associated with a reduction in lung cancer incidence in patients with COPD. Observational studies reporting such reduction may have been affected by time-related biases and the inclusion of patients with asthma. The proposition of a randomised trial warrants some caution.