Screening values of carcinoembryonic antigen and cytokeratin 19 fragment for lung cancer in combination with low-dose computed tomography in high-risk populations: Initial and 2-year screening outcomes

Objectives: To assess added screening value of Carcinoembryonic Antigen (CEA) and Cytokeratin 19 Fragment (CYFRA 21-1) in combination with LDCT beyond LDCT alone and likelihood ratio of positive (LHR+) of their combination for lung cancer in high-risk populations with indeterminate and positive LDCT after initial screening and 2-year follow up. Materials and methods: LDCT was performed annually at baseline and for 2 years in 634 heavy smokers (>30 pack-years) who were aged 50-70 years, and it was classified as negative, indeterminate, or positive (suspicious for lung cancer). Serum CEA and CYFRA 21-1 were examined and followed with LDCT in the indeterminate and positive LDCT groups and defined as positive with an abnormal level of either CEA or CYFRA 21-1. Results: A total of 17 lung cancer cases were diagnosed (9 from initial screening and 8 from follow-up cycles). Seventy and 22 patients had indeterminate and positive baseline LDCT, respectively. Among indeterminate baseline LDCT, the LHR+ for lung cancer diagnosed after initial screening with a positive marker was 6.61 (p=.039) and 1.51 (p=.502) with a negative marker. After 2 years follow up, the LHR+ was 6.31 (p=.004) and 0.86 (p=.677), respectively. Among positive baseline LDCT, the LHR+ for lung cancer diagnosed after initial round with positive and negative markers was 69.44 (p<0.001) and 11.57 (p=.015), respectively. The corresponding LHR+ after 2-year round was 13.61 (p=.002) and 18.15 (p=.001), respectively. The combinations of CEA/CYFRA 21-1 and LDCT, and CEA and LDCT had crude and adjusted added value beyond LDCT alone (crude: 8%, p=.033 and 7%, p=.038; adjusted: 4%, p=.019 and 4%, p=.029, respectively). Conclusions: CEA in combination with LDCT significantly increases the value of lung cancer screening compared with using LDCT alone particularly in participants with indeterminate baseline LDCT in both initial and 2-year screening outcomes.