Overdiagnosis in lung cancer screening - estimates from the German Lung Cancer Screening Intervention Trial.

González Maldonado, Sandra; Motsch, Erna; Trotter, Anke; Kauczor, Hans-Ulrich; Heussel, Claus-Peter; Hermann, Silke; Zeissig, Sylke Ruth; Delorme, Stefan; Kaaks, Rudolf

Overdiagnosis is a major potential harm of lung cancer screening; knowing its potential magnitude helps to optimize screening eligibility criteria. The German Lung Screening Intervention Trial ("LUSI") is a randomized trial among 4052 long-term smokers (2622 men), 50.3-71.9 years of age from the general population around Heidelberg, Germany, comparing five annual rounds of low-dose computed tomography (n=2029) with a control arm without intervention (n=2023). After a median follow-up of 9.77 years post-randomization and 5.73 years since last screening, 74 participants were diagnosed with lung cancer in the control arm and 90 in the screening arm: 69 during the active screening period; of which 63 screen-detected and 6 interval cancers. The excess cumulative incidence in the screening arm (N=16) represented 25.4% [95%CI -11.3, 64.3] of screen-detected cancer cases (N=63). Analyzed by histologic subtype, excess incidence in the screening arm appeared largely driven by adenocarcinomas. Statistical modeling yielded an estimated mean pre-clinical sojourn time (MPST) of 5.38 [4.76, 5.88] years and a screen-test sensitivity of 81.6 [74.4%, 88.8%] for lung cancer overall, all histologic subtypes combined. Based on modeling, we further estimated that about 48% (47.5% [43.2%, 50.7%]) of screen-detected tumors have a lead time ≥4 years, whereas about 33% (32.8% [28.4%, 36.1%]) have a lead time ≥6 years, 23% (22,6% [18,6%, 25,7%]) ≥8 years, 16% (15.6% [12,2%, 18,3%]) ≥10 years and 11% (10,7% [8,0%, 13,0%]) ≥12 years. The high proportions of tumors with relatively long lead times suggests a major risk of overdiagnosis for individuals with comparatively short remaining life expectancies. This article is protected by copyright. All rights reserved.