Potential missed diagnostic opportunities after low dose CT screening for lung cancer: results from the National Lung Cancer Screening Trial

Abstract Objectives Low-dose CT (LDCT) screening is critical for early lung cancer detection. We assessed diagnostic uncertainty following positive LDCTs in the National Lung Screening Trial (NLST). We defined this pathway as an “Potential missed diagnostic opportunity” for participants eventually diagnosed with lung cancer. Methods This is a secondary analysis of the NLST trial, examining potential missed diagnostic opportunity among screen-detected participants who were diagnosed with lung cancer in the LDCT arm. Potential missed diagnostic opportunity (PMDO) defined as no lung cancer diagnosis following a positive LDCT, which was then followed by a subsequent annual positive LDCT that did lead to lung cancer diagnosis. Results Of 1,089 lung cancers diagnosed in the LDCT arm, 58 % (630 individuals) were adherent screen-detected at risk for a PMDO (605 55 % using Lung-RADS). Overall, 37.3 % (235 of 630) experienced ≥1 PMDO (33.1 % using Lung-RADS). Among the 235 participants who experienced a PMDO , only 1.7 % (four individuals) received a diagnostic resection or biopsy, and 35.7 % (84 individuals) had little to no diagnostic procedures following their first positive LDCT. Once diagnosed, the group that experienced PMDO tended to have earlier stage lung cancer and longer survival rates compared to those without such events. Conclusions While LDCT is a vital screening tool, a substantial proportion of lung cancer patients experience a period of diagnostic uncertainty after an initial positive screen. This pathway highlights a critical area for process improvement. Understanding the clinical decision-making during these periods is essential to fully optimize the benefits of early detection.