Overdiagnosis in lung cancer screening: Estimates from the German Lung Cancer Screening Intervention Trial

Abstract

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 to 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 postrandomization 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% confidence interval: −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 preclinical 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 suggest a major risk of overdiagnosis for individuals with comparatively short remaining life expectancies.

Lung function impairment in the German Lung Cancer Screening Intervention Study (LUSI): prevalence, symptoms, and associations with lung cancer risk, tumor histology and all-cause mortality

“…However, similar to NLST-ACRIN findings, our data did suggest histology and stage shifts for lung cancer patients who had abnormal spirometry, notably so in the COPD and PRISm groups. Several screening studies ( 48 - 51 ), including LUSI ( 36 ), found an increased proportion of adenocarcinomas among early-stage lung tumors detected by CT screening, likely because these are more slowly growing tumors, detectable over a longer period prior to clinical manifestation ( 52 , 53 ), and because of their more peripheral location in the lungs, where small nodules are detected more easily. Analyses of the full NLST trial data by sex and by tumor histology ( 48 ) showed that non-small cell and non-squamous cell tumors, notably adenocarcinomas, likely are the tumor subtypes most associated with reduced mortality upon early detection by CT screening.…”

9G TestTM Cancer/Lung: A Desirable Companion to LDCT for Lung Cancer Screening

“…Though community screening is vital to identify lung cancer patients at stage 0~I, overdiagnosis in terms of false-positive results is a troubling aspect of cancer screening [6][7][8]. Conventionally, chest X-ray (CXR) and sputum cytology are used for the screening for lung neoplasms.…”

Design and Rationale of the HANSE Study: A Holistic German Lung Cancer Screening Trial Using Low-Dose Computed Tomography

“…New lung cancer cases will be verified using official hospital or cancer registry documents. The minimum follow-up period of 5 years was chosen to account for the sojourn-time bias 25 between tumor and symptom occurrence and cancer diagnosis in the low-risk group.…”