Incidentally-Detected Lung Cancer in Persons Too Young or Too Old for Lung Cancer Screening in a Mississippi Delta Cohort.

Lung cancer risk in screening age-ineligible persons with incidentally-detected lung nodules is poorly characterized. We evaluated lung cancer risk in two age-ineligible Lung Nodule Program (LNP) cohorts. Prospective observational study comparing 2-year cumulative lung cancer diagnosis risk, lung cancer characteristics and overall survival (OS) between low-dose CT (LDCT) screening participants aged 50-80 years and LNP participants aged 35 - <50 years (young) and >80 years (elderly). From 2015 to 2022, lung cancer was diagnosed in 329 (3.43%), 39 (1.07%) and 172 (6.87%) LDCT, young and elderly LNP patients, respectively. Two-year cumulative incidence was 3.0% (95% CI: 2.6%-3.4%) versus 0.79% (CI: 0.54%-1.1%) versus 6.5% (CI: 5.5%-7.6%), respectively, but lung cancer diagnosis risk was similar between young LNP and Lung-RADS 1 (aHR 0.88 [CI: 0.50-1.56]) and 2 (aHR 1.0 [0.58-1.72]). Elderly LNP risk was greater than Lung-RADS 3 (aHR 2.34 [CI: 1.50-3.65]), but less than 4 (aHR 0.28 [CI: 0.22-0.35]). Lung cancer was stage I/II in 62.92% of LDCT versus 33.33% of young (p=0.0003) and 48.26% of elderly (p=0.0004) LNP cohorts; 16.72%, 41.03% and 29.65%, respectively were diagnosed at stage IV. Aggregate 5-year OS rates were 57% (CI: 48-67), 55% (CI: 39-79) and 24% (CI: 15-40) (Log-rank p<0.0001). Results were similar after excluding persons with any history of cancer. LNP modestly benefited persons too young or old for screening. Differences in clinical characteristics and outcomes suggest differences in biologic characteristics of lung cancer in these three patient cohorts.

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