• Division of Pulmonary and Critical Care Medicine, Henry Ford Health System, Detroit, MI, United States. Electronic address: pkvale1@hfhs.org.
• Department of Public Health Sciences, Henry Ford Health System, Detroit, MI, United States. Electronic address: cjohnso1@hfhs.org.
• Department of Community Health Sciences, Brock University, St. Catharines, Ontario, Canada. Electronic address: martin.tammemagi@brocku.ca.
• National Cancer Institute, Bethesda, MD, United States. Electronic address: marcusp@mail.nih.gov.
• Department of Radiology, Henry Ford Health System, Detroit, MI, United States. Electronic address: zylak@rad.hfh.edu.
• Department of Radiology, Henry Ford Health System, Detroit, MI, United States. Electronic address: davidl@rad.hfh.edu.
• Department of Clinical Oncology, Marshfield Clinic, Marshfield, WI, United States. Electronic address: hocking.william@marshfieldclinic.org.
• Division of Environmental Health Sciences, School of Public Health, University of Minnesota, Minneapolis, MN, United States. Electronic address: travelermmo@yahoo.com.
• Information Management Services, Inc., Rockville, MD, United States. Electronic address: comminsj@imsweb.com.
• Westat, Inc., Rockville, MD, United States. Electronic address: lawrenceragard@westat.com.

BACKGROUND: The Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial provides us an opportunity to describe interval lung cancers not detected by screening chest X-ray (CXR) compared to screen-detected cancers.

METHODS: Participants were screened for lung cancer with CXR at baseline and annually for two (never smokers) or three (ever smokers) more years. Screen-detected cancers were those with a positive CXR and diagnosed within 12 months. Putative interval cancers were those with a negative CXR screen but with a diagnosis of lung cancer within 12 months. Potential interval cancers were re-reviewed to determine whether lung cancer was missed and probably present during the initial interpretation or whether the lesion was a "true interval" cancer.

RESULTS: 77,445 participants were randomized to the intervention arm with 70,633 screened. Of 5227 positive screens from any screening round, 299 resulted in screen-detected lung cancers; 151 had potential interval cancers with 127 CXR available for re-review. Cancer was probably present in 45/127 (35.4%) at time of screening; 82 (64.6%) were "true interval" cancers. Compared to screen-detected cancers, true interval cancers were more common among males, persons with <12 years education and those with a history of smoking. True interval lung cancers were more often small cell, 28.1% vs. 7.4%, and less often adenocarcinoma, 25.6% vs. 56.2% (p<0.001), more advanced stage IV (30.5% vs. 16.6%, p<0.02), and less likely to be in the right upper lobe, 17.1% vs. 36.1% (p<0.02).

CONCLUSION: True interval lung cancers differ from CXR-screen-detected cancers with regard to demographic variables, stage, cell type and location. ClinicalTrials.gov number: NCT00002540.