Abstract Rationale Interval cancers, diagnosed between rounds of lung cancer screening, often have aggressive tumor biology and worse oncologic outcomes. This represents an opportunity to investigate lung cancer (LC) risk factors and optimize screening strategies. We carried out a retrospective analysis of LC diagnoses among patients receiving screening through our centralized LCS Program. Methods We track LCS Program participants prospectively in our LCS Registry for screening-detected LC diagnosis; these cases were confirmed and additional LC diagnoses for individuals screened between January 2018-October 2025 were identified from the electronic health record using ICD-10 code 34.0. All LC cases were classified as either Screening-Detected (including Prevalence and Incidence LC) or Non-Screening-Detected (Non-SDCs) (including Interval and Non-Interval LC). Cases identified through the LCS Registry were classified as Screening-Detected LC, while diagnoses not present in the Registry were classified by manual chart review. Interval LC was defined using the IASLC recommendation, LC diagnosed after negative low-dose CT (LDCT) and within the interval recommended for next scheduled screening examination. We performed descriptive statistics, t-tests, and chi-square tests to compare groups. Results Among 165 LC diagnosed in the LCS Program cohort, Screening-Detected LC comprised 72.7% (n = 120) of cases. Among these, 54 (45.0%) were Prevalence LC detected on baseline LDCT and 66 (55.0%) were Incidence LC detected on subsequent LDCT (T1:26.7%, T2:10.8%, T3:8.3%). There were no significant differences in age, gender, race, smoking status, pack-years, insurance status, educational attainment, BMI, Chronic Obstructive Pulmonary Disease (COPD), or personal/family cancer history between the Prevalence and Incidence LC subgroups. Compared with the Screening-Detected LC group, Non-SDCs overall had significantly older age (mean, 70.0y±6.4 vs. 66.9y±5.7, p = 0.003) and greater smoking pack-years (mean, 65.6±29.2 vs. 53.7±26.2, p = 0.013). Additionally, small cell histology and stage IV LC diagnosis occurred approximately twice as often among Non-SDCs (17.8% vs. 9.2%; 20.0% vs. 10.0%, respectively); there was no difference in molecular alterations (Table). Four cases were classified as Interval LC, and included a high proportion of patients who currently smoke (75.0%), COPD (100.0%), very high pack-years (84.8±29.1) and small cell histology (100.0%). Conclusions This retrospective analysis demonstrates that interval LC diagnosed among screening participants comprise a very small proportion and occur in individuals at higher lung cancer risk, particularly those with very high smoking intensity. This could support tailoring evaluation of LDCT findings toward a more intensive management strategy for highest-risk individuals. Planned future analyses will include LC cases from 6 centralized LCS Programs across a health system. This abstract is funded by: none
Shusted et al. (Fri,) studied this question.