Lung Cancer Screening: Cumulative Risk and Multilevel Impact of False Positive Findings

ABSTRACT The National Lung Screening Trial demonstrated the efficacy of lung cancer screening (LCS) with low-dose computed tomography in reducing 5-year lung cancer mortality by 20%, albeit with high rates of false-positive results. The US Preventive Services Task Force recommends annual LCS with LDCT for individuals ages 50-

80-years who currently or formerly (quit within 15-years) smoked with a 20-pack-year history. Despite the task force Grade B recommendation, a major concern of LCS is the potential harm associated with false-positive results which are defined as having one or more nodules requiring follow-up and no change or lung cancer

diagnosis after one year. Specifically, false positives may burden the patient, clinician, and healthcare system due to the economic and psychological effects of extra imaging and invasive procedures, fear of missing cancer, and complications from procedures for benign lesions. There is a need to better estimate the burden

and the factors that affect false positive results in real-world practice over multiple rounds of screening to inform patient-clinician conversations, guide the development of interventions to reduce false positive rates, and optimize the risk-benefit ratio of LCS. The primary objective of this proposal is to identify the burden of

false-positive results at the patient, clinician, and facility levels and to understand the impact of false-positives across the screening continuum. Using rich sources of longitudinal LCS data for >40K LCS exams from 17 facilities linked with state-based cancer registry data, we will accomplish the objectives through the

following specific aims (1) Identify attitudes, knowledge, and experiences with false-positive results from LCS among patients and clinicians; (2) Determine patient-, exam-, radiologist-, and facility-level factors that affect false-positive findings on lung cancer screening; (3) Assess the cumulative risk of a false-positive LCS exam

over 5- and 10- rounds of annual screening across multilevel factors. An estimated 14.5 million US adults are eligible for LCS and are at risk of experiencing a false positive result. This study will generate in-depth knowledge about the potential harms of false-positive LCS results. These findings may inform patient-clinician

shared decision-making conversations or may help to reduce false positive rates by identifying modifiable radiologist or facility-level factors.