Cytisine for Smoking Cessation Within a Lung Cancer Screening Program: Results From the Italian RISP Trial

Background: Tobacco cessation support should be offered to all participants with active tobacco use within lung cancer (LC) screening programs. Among the pharmacologic options, cytisine is effective and safe, although data in individuals aged ≥65 years remain limited. Methods: From September 2022, all participants with active tobacco use enrolled in the RISP LC screening trial were offered a smoking cessation program, with optional cytisine treatment (1.5 mg in an escalating/de-escalating schedule). The primary end point was self-reported continuous smoking abstinence during the 2-week period following completion of the smoking cessation program, assessed at predefined counseling visits or through telephone follow-up when needed. Secondary end points included cigarette consumption reduction, feasibility of a cessation program within the Italian healthcare system, and cytisine safety. Results: Overall, 10,191 participants were enrolled; 7,805 had current smoking history, of whom 3,548 (45.5%) pursued a tobacco cessation program and 1,375 (38.7%) accepted cytisine treatment. The smoking cessation rate was 50.1% among cytisine users vs. 8.1% for counseling alone (n=2,173), p<0.05, adjusted odds ratio: 14.53 (95% CI: 11.67-18.08). The cytisine group showed greater reduction in cigarette consumption (23.4% vs. 10.0%, p<0.0001). Cytisine uptake was associated with greater smoking exposure (pack-years, baseline exhaled CO) and motivation for smoking cessation (all p<0.05). The most frequent adverse events (AEs) were nausea (36.2%), insomnia (19.0%), and abdominal discomfort (18.1%). Efficacy and toxicity were similar in volunteers ≥65 years (n=428, 31.1%), while women experienced more AEs, in particular abdominal discomfort (p<0.05). Dropouts occurred in 15.0% of cytisine users, 28.0% of whom experienced ≥1 AE. Conclusions: This is the largest analysis of cytisine use within an LC screening program, providing supportive evidence of its potential effectiveness and safety profile, including in adults ≥65 years.