Highlight
- The CASTL trial evaluated 16 combinations of tobacco cessation components among smokers scheduled for lung cancer screening in the U.S.
- Loss-framed messaging combined with nicotine patch and lozenge demonstrated the highest value-efficiency, with an expected 30% abstinence at a cost of $287.41.
- Gain-framed messaging alone offered a low-cost alternative with 13% abstinence at $51.29.
- High dependency was evident, with 79% of participants smoking within 30 minutes of waking.
Study Background
Lung cancer remains the leading cause of cancer death globally and in the United States. Early detection via low-dose computed tomography lung cancer screening (LCS) has become an important tool for reducing mortality in high-risk populations. However, nearly half of the estimated 14 million people eligible for LCS continue to smoke, which not only increases their risk but also compounds health issues. Smoking cessation is a critical adjunct to screening, yet optimal tobacco cessation strategies integrated within the LCS context have not been well defined. The Cessation and Screening to Save Lives (CASTL) trial was designed to address this gap by systematically testing combinations of cessation interventions to identify the most effective and cost-efficient strategies for this high-risk group.
Study Design
CASTL was an optimization randomized clinical trial conducted across 17 lung cancer screening sites in the United States. Eligible participants were adults aged 50 to 80, current smokers scheduled for lung cancer screening. A total of 758 participants were randomized to receive one of 16 intervention combinations derived from four tobacco treatment components: enhanced standard care, motivational interviewing, nicotine replacement therapy (patch and lozenge), and message framing (loss-framed or gain-framed). The primary endpoint was self-reported smoking abstinence at 6 months post-intervention. Cost analyses included time and resource expenditure for each intervention combination, with value efficiency defined by the balance between abstinence rates and intervention costs.
Key Findings
At enrollment, participant commitment to quitting varied, with 5% not interested, 59% contemplating quitting, and 38% actively modifying smoking behaviors. Nicotine dependence was notably high; 79% of smokers reported smoking within 30 minutes of waking, highlighting a group with significant addiction challenges.
Outcome analysis revealed no statistically significant differences in smoking abstinence rates across the 16 intervention combinations. Nevertheless, examining value efficiency identified that the most cost-effective strategy for promoting abstinence combined loss-framed messaging with nicotine patch and lozenge treatment, reaching an expected 30% abstinence rate at a mean intervention cost of $287.41. This approach emphasized the risks of continued smoking, which may resonate strongly with screened individuals concerned about lung cancer risk.
For settings with more constrained resources, a less expensive yet relatively effective alternative was gain-framed messaging alone, associated with 13% abstinence at a cost of $51.29. Gain-framed approaches highlight benefits of quitting rather than risks of continuing. Motivational interviewing and enhanced standard care components did not significantly improve abstinence outcomes when added to these messaging and pharmacotherapy strategies.
The findings underscore that integrating pharmacotherapy with targeted behavioral messaging enhances cessation success in the screening context, while complex or resource-intensive interventions do not necessarily yield additional benefit.
Expert Commentary
The CASTL trial advances understanding of tobacco cessation strategies tailored for lung cancer screening populations, an area of critical clinical importance. The approximately 30% abstinence rate with loss-framed messaging plus nicotine replacement is clinically meaningful, especially considering the high level of addiction among participants. These results reinforce current guidelines advocating for combining pharmacotherapy with behavioral support but add nuance by identifying message framing as a key component shaping intervention efficiency.
Limitations include reliance on self-reported abstinence without biochemical verification, which may introduce bias. Additionally, the generalizability to populations outside the U.S. or with different demographic characteristics requires caution. Long-term abstinence beyond six months and impacts on lung cancer outcomes remain to be studied. Nevertheless, CASTL offers a practical framework for delivering cost-effective cessation services within LCS programs.
Conclusion
The CASTL trial identifies loss-framed messaging combined with nicotine patch and lozenge as the most value-efficient tobacco cessation intervention for people seeking lung cancer screening who currently smoke. This approach balances efficacy and cost, fitting well into clinical workflows for LCS. For resource-limited settings, gain-framed messaging alone also achieves a modest cessation benefit at low cost. Integrating these findings into lung cancer screening programs could improve smoking cessation rates and thereby reduce lung cancer morbidity and mortality. Future research should aim to validate these strategies with biochemical confirmation and explore long-term outcomes.
Funding and Registration
The trial was conducted with funding from the National Cancer Institute and additional institutional resources. The clinical trial is registered under ClinicalTrials.gov identifier NCTXXXXXXX.
References
- Ostroff JS, Shelley D, Chichester LR, et al. An Optimization Randomized Clinical Trial to Identify an Effective, Efficient Smoking Cessation Intervention in the Context of Lung Cancer Screening: Cessation and Screening to Save Lives (CASTL). Chest. 2026 Jul 8. PMID: 42419585.
- U.S. Preventive Services Task Force. Screening for Lung Cancer: US Preventive Services Task Force Recommendation Statement. JAMA. 2021;325(10):962-970.
- Fiore MC, Jaén CR, Baker TB, et al. Treating Tobacco Use and Dependence: 2008 Update Clinical Practice Guideline. Rockville, MD: U.S. Dept. of Health and Human Services; 2008.