Abstract
Background Lung cancer screening with low-dose chest CT (LDCT) reduces the mortality of eligible individuals. Bloodsignatures might act as a standalone screening tool, refine the selection of patients at risk, or help to classifyundetermined nodules detected on LDCT. We previously showed that circulating tumour cells (CTCs) could bedetected, using the isolation by size of epithelial tumour cell technique (ISET), long before the cancer was diagnosedradiologically. We aimed to test whether CTCs could be used as a biomarker for lung cancer screening.Methods We did a prospective, multicentre, cohort study in 21 French university centres. Participants had to beeligible for lung cancer screening as per National Lung Screening Trial criteria and have chronic obstructivepulmonary disease with a fixed airflow limitation defined as post-bronchodilator FEV1/FVC ratio of less than 0∙7.Any cancer, other than basocellular skin carcinomas, detected within the previous 5 years was the main exclusioncriterion. Participants had three screening rounds at 1-year intervals (T0 [baseline], T1, and T2), which involved LDCT,clinical examination, and a blood test for CTCs detection. Participants and investigators were masked to the results ofCTC detection, and cytopathologists were masked to clinical and radiological findings. Our primary objective was totest the diagnostic performance of CTC detection using the ISET technique in lung cancer screening, compared withcancers diagnosed by final pathology, or follow up if pathology was unavailable as the gold standard. This studyis registered with ClinicalTrials.gov identifier, number NCT02500693.Findings Between Oct 30, 2015, and Feb 2, 2017, we enrolled 614 participants, predominantly men (437 [71%]), aged65∙1 years (SD 6∙5), and heavy smokers (52∙7 pack-years [SD 21∙5]). 81 (13%) participants dropped out betweenbaseline and T1, and 56 (11%) did between T1 and T2. Nodules were detected on 178 (29%) of 614 baseline LDCTs.19 participants (3%) were diagnosed with a prevalent lung cancer at T0 and 19 were diagnosed with incident lungcancer (15 (3%) of 533 at T1 and four (1%) of 477 at T2). Extrapulmonary cancers were diagnosed in 27 (4%) ofparticipants. Overall 28 (2%) of 1187 blood samples were not analysable. At baseline, the sensitivity of CTC detectionfor lung cancer detection was 26∙3% (95% CI 11∙8–48∙8). ISET was unable to predict lung cancer or extrapulmonarycancer development.