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

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 and older remain limited.

From September 2022, all participants with active tobacco use enrolled in the Rete Italiana Screening Polmonare (RISP) LC screening trial were offered a smoking cessation program, with optional cytisine treatment (1.5 mg on an escalating and deescalating schedule). The primary end point was self-reported continuous smoking abstinence during the 2-week period after 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, the feasibility of a cessation program within the Italian health care system, and cytisine safety.

Overall, 10,191 participants were enrolled; 7805 had a current smoking history, of whom 3548 (45.5%) pursued a tobacco cessation program and 1375 (38.7%) accepted cytisine treatment. The smoking cessation rate was 50.1% among cytisine users versus 8.1% for those receiving counseling alone (n = 2173) (p <0.05), adjusted OR: 14.53 (95% confidence interval [CI]: 11.67-18.08). The cytisine group reported a greater reduction in cigarette consumption (23.4% versus 10.0%, p <0.0001). Cytisine uptake was associated with greater smoking exposure (pack-years, baseline exhaled carbon monoxide) 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 aged 65 years and older (n = 428, 31.1%); women experienced more AEs, particularly abdominal discomfort (p <0.05). Dropouts occurred in 15.0% of cytisine users; 28.0% of these experienced at least one AE.

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 aged 65 years and older.