A Moving Target: Integration of Smoking Cessation into Screening for Second Primary Lung Cancer

To the Editor:

We thank Drs. Pelosi and Pasini for their interest in our study¹ and for sharing important patient survival data that supports the critical need to offer smoking cessation guidance in tandem with lung cancer screening. These data build on our study results which identified tobacco smoking as a prominent risk factor for the development of second primary lung cancer (SPLC) among participants harboring an initial primary lung cancer (IPLC), as observed across three epidemiologic cohorts. In their analysis of 134 early-stage lung cancer patients who were disease-free at five years following surgical resection, Drs. Pelosi and Pasini found that 20 patients met criteria for SPLC during follow-up. Notably, all of these patients maintained a current smoking status after IPLC diagnosis. Excess mortality within the cohort was confined to deaths from lung cancer, which was nearly six times higher than expected, indicating that lung cancer-related mortality continues to have a non-negligible impact on patients with early-stage lung cancer beyond the 5-year benchmark used for assessing cure.

Another recent study evaluated the association between SPLC diagnosis and overall survival, and found that SPLC patients had a significantly decreased survival compared to matched IPLC patients without SPLC (median 3.63 years versus 7.31 years; p<0.001)². Although the role of tobacco smoking in mediating potential mortality differences needs to be elucidated, these data suggest that development of SPLC may be a poor prognostic factor in IPLC patients. Given the expected increase in lung cancer survivors owing to advances in early detection and therapeutics, strategies for preventing and identifying SPLCs early on are imperative to optimize cancer care.

Currently, there is limited evidence on how to best incorporate smoking cessation support into lung cancer screening. As one of their study objectives, the randomized controlled 4-IN THE LUNG RUN trial aims to develop and integrate personalized smoking cessation services into screening of high-risk populations in Europe³. Recognizing that early detection is not enough, this effort will be among the first to systematically incorporate IPLC prevention, through smoking cessation, in the optimization of lung cancer screening. In considering cessation implementation strategies, one relevant question concerns their impact on costs. A recent cost-effective analysis used a Cancer Intervention and Surveillance Modeling Network model to simulate individuals born in 1960 over their lifetimes in comparing annual screening with or without smoking cessation interventions⁴. Compared to screening alone, screening with smoking cessation interventions resulted in fewer lung cancer cases and deaths and increased life expectancy. Importantly, the added costs of providing a smoking cessation intervention to current smoking individuals eligible for screening were offset by future decreases in screening—by individuals who were no longer screen-eligible due to cessation—and reduced cancer treatment costs from having fewer lung cancer cases.

Our study provides initial data demonstrating that smoking cessation after IPLC diagnosis is associated with a reduced risk of SPLC (HR 0.17 95% CI 0.06-0.47). Together with emerging evidence of SPLC as a poor prognostic factor and the mortality reduction that cessation can have among lung cancer patients⁵, these data support SPLC screening in combination with smoking cessation programs with the potential for improving long-term survival. In the development and evaluation of evidence-based SPLC surveillance strategies, smoking cessation must be considered an integral component as we increasingly shift our focus towards the care of lung cancer survivors.