Estimating Overdiagnosis in Low-Dose Computed Tomography Screening for Lung Cancer

Background: Lung cancer screening may detect cancer that will never become symptomatic (overdiagnosis), leading to overtreatment. Changes in size on sequential low-dose computed tomography (LDCT) screening, expressed as volume-doubling time (VDT), may help to distinguish aggressive cancer from cases that are unlikely to become symptomatic. Objective: To assess VDT for screening-detected lung cancer as an indicator of overdiagnosis. Design: Retrospective estimation of the VDT of cancer detected in a prospective LDCT screening cohort. Setting: Nonrandomized, single-center screening study involving persons at high risk for lung cancer enrolled between 2004 and 2005 who received LDCT annually for 5 years. Patients: 175 study patients diagnosed with primary lung cancer. Measurements: VDT was measured on LDCT and classified as fast-growing (<400 days), slow-growing (between 400 and 599 days), or indolent (≥600 days). Results: Fifty-five cases of cancer were diagnosed at baseline, and 120 were diagnosed subsequently. Of the latter group, 19 cases (15.8%) were new (not visible on previous scans) and fast-growing (median VDT, 52 days); 101 (84.2%) were progressive, including 70 (58.3%) fast-growing and 31 (25.8%) slow-growing (15.0%) or indolent (10.8%) cases. Lung cancer–specific mortality was significantly higher (9.2% per year) in patients with new compared with slow-growing or indolent (0.9% per year) cancer. Sixty percent of fast-growing progressive cancer and 45% of new cancer were stage I, for which survival was good. Limitations: This is a retrospective study. Volume-doubling time can only indicate overdiagnosis and was estimated for new cancer from 1 measurement (a diameter of 2 mm assumed the previous year). Conclusion: Slow-growing or indolent cancer comprised approximately 25% of incident cases, many of which may have been overdiagnosed. To limit overtreatment in these cases, minimally invasive limited resection and nonsurgical treatments should be investigated. Primary Funding Source: Italian Association for Cancer Research.