Abstract 4919: Evaluation of lung cancer risk and screening strategies for individuals who quit smoking more than 15 years ago

Abstract The U.S. Preventive Services Task Force (USPSTF) recommends lung cancer screening for individuals who currently or formerly smoked with at least 20 pack-years of smoking and quit less than 15 years ago. However, the number of former smokers now surpasses that of current smokers in the U.S., recently, the American Cancer Society (ACS) recommended removing the quit-year exclusion criterion for lung cancer screening eligibility. Little is known for about lung cancer risk in long-term former smokers, and the optimal criterion to identify high-risk long-term former smokers is uncertain. Our analysis included 424,483 long-term former smokers (>15 quit years) aged 40 to 80 years from the Lung Cancer Cohort Consortium (LC3) with detailed risk factors information and lung cancer incidence data from 24 prospective cohorts. We evaluated the validity of the PLCOm2012 risk model by estimating model calibration (E/O: ratio-of-expected to observed number of cases) and discrimination (AUC) in long-term former smokers. We considered individuals with six-year-risk above 1.0% as high risk, using the PLCOm2012 model. The 1.0% risk threshold was defined to identify a similar number of LDCT screening eligible individuals as the USPSTF2021 criteria. We further compared the effectiveness of the ACS criteria (i.e. USPSTF2021 without 15-year quit year exclusion) and the PLCOm2012 model in identifying future lung cancer cases and deaths in long-term former smokers. Among long-term former smokers, the PLCOm2012 model showed good risk discrimination with AUC of 0.78 (95% CI: 0.77-0.79) but underpredicted the overall lung cancer risk (E/O: 0.72; 95% CI: 0.70-0.74). The PLCOm2012 model indicated that 20.0% of long-term former smokers (N=85,041) had six-year-risk above 1.0%, which identified 62.0% (N=2,035) of lung cancers and 64.0% (N=1,169) of lung cancer deaths within 5 years in this population. The ACS criteria identified 31% of long-term former smokers as screening eligible (N=131,225), which identified 69.0% (N=2264) of lung cancers and 70.9% (N=1,294) of lung cancer deaths occurring within 5 years. When using the PLCOm2012 model to define eligibility, applying a threshold that selected a population of equal size to ACS criteria (6y risk ≥0.63%), 75.2% (N=2,469) of lung cancers and 76.4% (N=1,395) of lung cancer deaths would be identified in this group. Our findings suggest that at least 20% of long-term former smokers are at high risk and may benefit from LDCT screening. Removing the 15-year quit-year exclusion would identify over two-thirds of lung cancer cases, by screening one-third of long-term former smokers. A risk-based approach to prioritize a subset of long-term former smokers for screening may be more efficient than age and pack-year criteria. These results provide insight into the benefits of expanding current screening criteria to include long-term former smokers. Citation Format: Hanla A. Park, Karine Alcala, James McKay, Mattias Johansson, Hilary A. Robbins, Xiaoshuang Feng, Lung Cancer Cohort Consortium. Evaluation of lung cancer risk and screening strategies for individuals who quit smoking more than 15 years ago [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4919.