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Overdiagnosis of lung cancer with low-dose computed tomography screening: meta-analysis of the randomised clinical trials

John Brodersen, Theis Voss, Frederik Martiny, Volkert Siersma, Alexandra Barratt, Bruno Heleno
Breathe 2020 16: 200013; DOI: 10.1183/20734735.0013-2020
John Brodersen
1The Section of General Practice and the Research Unit for General Practice, Dept of Public Health, University of Copenhagen, Copenhagen, Denmark
2The Research Unit for General Practice in Region Zealand, Sorø, Denmark
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  • For correspondence: jobr@sund.ku.dk
Theis Voss
1The Section of General Practice and the Research Unit for General Practice, Dept of Public Health, University of Copenhagen, Copenhagen, Denmark
2The Research Unit for General Practice in Region Zealand, Sorø, Denmark
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Frederik Martiny
1The Section of General Practice and the Research Unit for General Practice, Dept of Public Health, University of Copenhagen, Copenhagen, Denmark
2The Research Unit for General Practice in Region Zealand, Sorø, Denmark
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Volkert Siersma
1The Section of General Practice and the Research Unit for General Practice, Dept of Public Health, University of Copenhagen, Copenhagen, Denmark
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Alexandra Barratt
3Sydney School of Public Health, University of Sydney, Sydney, Australia
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Bruno Heleno
4CEDOC, Chronic Diseases Research Centre, NOVA Medical School, Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, Lisbon, Portugal
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Abstract

In low-dose computed tomography (LDCT) screening for lung cancer, all three main conditions for overdiagnosis in cancer screening are present: 1) a reservoir of slowly or nongrowing lung cancer exists; 2) LDCT is a high-resolution imaging technology with the potential to identify this reservoir; and 3) eligible screening participants have a high risk of dying from causes other than lung cancer. The degree of overdiagnosis in cancer screening is most validly estimated in high-quality randomised controlled trials (RCTs), with enough follow-up time after the end of screening to avoid lead-time bias and without contamination of the control group.

Nine RCTs investigating LDCT screening were identified. Two RCTs were excluded because lung cancer incidence after the end of screening was not published. Two other RCTs using active comparators were also excluded. Therefore, five RCTs were included: two trials were at low risk of bias, two of some concern and one at high risk of bias. In a meta-analysis of the two low risk of bias RCTs including 8156 healthy current or former smokers, 49% of the screen-detected cancers were overdiagnosed. There is uncertainty about this substantial degree of overdiagnosis due to unexplained heterogeneity and low precision of the summed estimate across the two trials.

Key points

  • Nine randomised controlled trials (RCTs) on low-dose computed tomography screening were identified; five were included for meta-analysis but only two of those were at low risk of bias.

  • In a meta-analysis of recent low risk of bias RCTs including 8156 healthy current or former smokers from developed countries, we found that 49% of the screen-detected cancers may be overdiagnosed.

  • There is uncertainty about the degree of overdiagnosis in lung cancer screening due to unexplained heterogeneity and low precision of the point estimate.

  • If only high-quality RCTs are included in the meta-analysis, the degree of overdiagnosis is substantial.

Educational aims

  • To appreciate that low-dose computed tomography screening for lung cancer meets all three main conditions for overdiagnosis in cancer screening: a reservoir of indolent cancers exists in the population; the screening test is able to “tap” this reservoir by detecting biologically indolent cancers as well as biologically important cancers; and the population being screened is characterised by a relatively high competing risk of death from other causes

  • To learn about biases that might affect the estimates of overdiagnosis in randomised controlled trials in cancer screening

Abstract

In low-dose computed tomography (LDCT) screening for lung cancer, all three main reasons for overdiagnosis are present. Half of people detected as having lung cancer via their participation in LDCT screening are overdiagnosed. http://bit.ly/32tLZk4

Footnotes

  • Supplementary material This article has supplementary material available from breathe.ersjournals.com.

  • Author contributions J. Brodersen, T. Voss and B. Heleno conceived and designed this meta-analysis. J. Brodersen, T. Voss, F. Martiny and B. Heleno acquired, analysed and interpreted the data. J. Brodersen and B. Heleno drafted the manuscript: J.Brodersen, T. Voss, F. Martiny, V. Siersma, A. Barratt and B. Heleno critically revised the manuscript for important intellectual content.

  • Conflict of interest: J. Brodersen is a member of the Danish Lung Cancer Screening Trial steering committee. Besides that, he has nothing to disclose.

  • Conflict of interest: T. Voss has nothing to disclose.

  • Conflict of interest: F. Martiny has nothing to disclose.

  • Conflict of interest: V. Siersma has nothing to disclose.

  • Conflict of interest: A. Barratt has nothing to disclose.

  • Conflict of interest: B. Heleno has nothing to disclose.

  • Received January 20, 2020.
  • Accepted February 22, 2020.
  • Copyright ©ERS 2020
http://creativecommons.org/licenses/by-nc/4.0/

Breathe articles are open access and distributed under the terms of the Creative Commons Attribution Non-Commercial Licence 4.0.

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Overdiagnosis of lung cancer with low-dose computed tomography screening: meta-analysis of the randomised clinical trials
John Brodersen, Theis Voss, Frederik Martiny, Volkert Siersma, Alexandra Barratt, Bruno Heleno
Breathe Mar 2020, 16 (1) 200013; DOI: 10.1183/20734735.0013-2020

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Overdiagnosis of lung cancer with low-dose computed tomography screening: meta-analysis of the randomised clinical trials
John Brodersen, Theis Voss, Frederik Martiny, Volkert Siersma, Alexandra Barratt, Bruno Heleno
Breathe Mar 2020, 16 (1) 200013; DOI: 10.1183/20734735.0013-2020
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