• Division of Cancer Prevention and Genetics, IEO European Institute of Oncology IRCCS, Milan, Italy.
• Division of Epidemiology and Biostatistics, IEO European Institute of Oncology IRCCS, Milan, Italy.
• Division of Thoracic Surgery, IRCCS San Raffaele Scientific Institute, Milan, Italy.
• Department of Medical Imaging and Radiation Sciences, IEO European Institute of Oncology IRCSS, Milan, Italy.
• IEO European Institute of Oncology IRCCS, Milan, Italy.
• Department of Oncology and Hemato-oncology, University of Milan, Milan, Italy.
• Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
• Division of Cancer Prevention, National Cancer Institute, Bethesda, MD, USA.

Lung cancer screening by helical low-dose computed tomography detects nonsolid nodules that may be lung adenocarcinoma precursors. Aspirin's anti-inflammatory properties make it an attractive target for prevention of multiple cancers, including lung cancer. Therefore, we conducted a phase IIb trial (NCT02169271) to study the efficacy of low-dose aspirin to reduce the size of subsolid lung nodules (SSNs). A total of 98 current or former smokers (67.3% current) undergoing annual low-dose computed tomography screening with persistent SSNs were randomly assigned to receive aspirin 100 mg/day or placebo for 1 year. There was no difference in change in the sum of the longest diameters of target nodules in the placebo and aspirin arm after 12 months of treatment (-0.12 mm [SD = 1.55 mm] and +0.30 mm [SD= 2.54 mm], respectively; 2-sided P = .33 primary endpoint). There were no changes observed in subgroup analyses by individual characteristics or nodule type. One year of low-dose aspirin did not show any effect on lung SSNs. SSNs regression may not be the proper target for aspirin, and/or longer duration may be needed to see SSNs modifications.