Combined low-dose thoracic computed tomography and circulating tumor cell screening for cancer in ever smokers with peripheral arterial disease: A prospective multicenter cohort study.

OBJECTIVE: Patients with peripheral arterial disease (PAD) present a high risk of cancer-related mortality. We aimed to evaluate a screening approach combining low-dose thoracic computed tomography (LDCT) and circulating tumor cell (CTC) search for cancer detection in PAD patients. DESIGN: A prospective multicenter cohort study was conducted in France between January 1, 2017, and June 30, 2020. Eligible PAD patients were aged 55-80 years, with a smoking history ≥ 30 pack-years (current or smoking cessation within the past 15 years). METHODS: Three consecutive annual screening rounds were planned combining LDCT and CTC detection. Patients were followed-up for a total of three years. Primary outcome was the diagnostic performance of this combined screening strategy. RESULTS: Among 149 ever-smoker PAD patients enrolled (median age 66 years [60.4-71.0]; 114 [76.5 %] men), nine cancers were diagnosed at first screening round. After three years, a total of ten lung and eight extrapulmonary cancers were diagnosed in 18 patients (12.1 %): LDCT detected nine lung cancers and one extrapulmonary cancer (pulmonary metastasis), while CTCs were found in six lung cancer patients and in four with extrapulmonary cancer. Combined screening strategy allowed to detect ten lung cancers plus five of eight extrapulmonary cancers, yielding a sensitivity of 83.3 % (95 % CI 66.1-100) and specificity of 45.0 % (95 % CI 36.5-53.6). CONCLUSION: Ever smokers with PAD demonstrated a high prevalence of pulmonary and extrapulmonary cancers. Screening strategy combining LDCT and CTC detection may improve early diagnosis in this high-risk population. Larger studies are warranted to validate this approach in clinical screening programs.