Personalizing Veterans' Lung Cancer Screening and Diagnosis

Annual lung cancer screening with low-dose computed tomography (LDCT) is recommended by the U.S. Preventive Services Task Force (USPSTF) for individuals aged 50-80 years with a ≥20 pack-year smoking history who currently smoke or quit within the past 15 years. However, USPSTF eligibility criteria identify only an estimated 45-65% of lung cancers that are ultimately diagnosed. Veterans face an increased risk of lung cancer due to higher rates of tobacco use and additional service-related exposures, including Agent Orange, asbestos, burn pits, and ionizing radiation. This proof-of-concept, non-inferiority prospective cohort study aims to evaluate a personalized lung cancer screening protocol tailored to the Veteran population. We will enroll 1,400 Veterans across seven VA medical centers (Nashville, Denver, Louisville, Chicago, Kansas City, Salisbury, and Seattle). Eligible participants will be 50-80 years old, have any history of cigarette smoking, and possess at least one additional lung cancer risk factor (COPD diagnosis, prior tobacco-related cancer, family history of lung cancer, or the above service-related exposures). Participants will undergo annual LDCT screening interpreted using standard-of-care Lung-RADS criteria. The primary non-inferiority analysis will determine whether this expanded, Veteran-specific screening eligibility (experimental group) detects at least the same proportion of lung cancers as the historical cohort screened under USPSTF criteria within Lung Precision Oncology Program sites. A non-inferiority margin of 0.5% was selected based on clinical significance. Because broader eligibility will increase the number of indeterminate pulmonary nodules, the investigators will also assess whether a combined biomarker strategy can improve diagnostic efficiency. Among 520 Nashville Veterans with positive LDCT results, the investigators will test whether pairing image-based biomarkers with blood-based biomarkers reduces invasive procedures and shortens time to diagnosis compared with the Brock Model. We hypothesize that the Veteran-specific screening criteria will be non-inferior to USPSTF criteria in lung cancer incidence detected and that a combined biomarker approach will reduce unnecessary procedures and accelerate diagnostic timelines for Veterans with positive screening findings. This study will provide proof-of-concept evidence supporting personalized lung cancer screening for Veterans and the integration of biomarker-guided management for screen-detected indeterminate pulmonary nodules. This study also includes a Community Advisory Board (CAB) composed of Veterans, members of Veteran organizations, and Veteran family members (n=15). The purpose of the CAB is to incorporate Veteran perspectives on study progress. The CAB will also inform dissemination of all study results to the community, including any lay written report and presentations to the community. We will conduct semi-structured interviews (n=60 or until thematic saturation is reached) with Veterans who have undergone lung cancer screening as part of expanded criteria and usual screening criteria (USPSTF). These interviews will assess Veteran preferences for lung cancer screening outreach and engagement.