In people at risk of lung cancer, does population based CT screening reduce mortality?

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Note: This question was open for public comment from 19 August 2016 to 3 October 2016. This content is not part of the public consultation from 3-30 July 2017 and is therefore not open for comment.


Evidence - Screening with low dose CT

There is evidence that low dose computed tomography (LDCT) screening reduces lung cancer specific mortality and all-cause mortality in people at high risk of lung cancer. Evidence of lung cancer specific mortality reduction came from the National Lung Screening Trial (NLST) in the US which showed a 20% reduction, p=0.004[1] and also from a meta-analysis with a odds ratio of 0.84, 95% CI 0.74-0.96[2] using pooled data from four randomised trials, including NLST, Danish Lung Cancer Screening Trial (DLCST)[3][4], Detection and Screening of Early Lung Cancer by Novel Imaging Technology and Molecular Essays (DANTE trial)[5][6] and the Multicentric Italian Lung Detection study (MILD study)[7]. Evidence of all-cause mortality reduction came from the largest and high quality NLST study alone, which has a study population of 53,434, with their results showing a reduction of 6.7%, p=0.02.[1] The other smaller randomised trials (DLCST, DANTE and MILD) each had study populations of fewer than 5000 and did not have sufficient statistical power to demonstrate a statistically significant all-cause mortality reduction.

There however remain uncertainties and ongoing questions about the generalisability of these international trial results, and the cost effectiveness of LDCT screening in the Australian context.[8][2][9] (see also CT Screening) How best to implement lung cancer screening outside a research environment is also uncertain.

The currently available evidence is therefore insufficient to recommend population based LDCT screening in Australia, and we await future local studies to clarify the efficacy, cost effectiveness and feasibility of implementing such screening program in an Australian setting (see also 'Which population group would most benefit from CT screening for lung cancer?'). We also await further results from the existing screening trials with longer follow up time and pooled analysis of European screening trials to provide a sample size with adequate power to confirm the mortality reduction from LDCT.

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Evidence summary and recommendations

Evidence summary Level References
Computed tomography (CT) screening reduces lung cancer specific mortality in high risk patients. I, II [1], [2]
Computed tomography (CT) screening slightly reduces all-cause mortality in people at high risk for lung cancer. II [1]
There is no high level implementation studies in the Australian context supporting population-based CT screening. N/A
Evidence-based recommendationQuestion mark transparent.png Grade
There is insufficient evidence to recommend population-based CT Screening.*

* Despite the existing evidence from North America that computed tomography (CT) screening can reduce lung cancer specific and all-cause mortality in some people at high risk for lung cancer, current uncertainties including the generalisability of this international trial result to the Australian setting, the lack of local cost effectiveness evidence, and concerns as how best to implement a safe and effective screening program in Australia, mean that the available evidence is insufficient to recommend population based CT screening in Australia at the current time.

B


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Issues requiring more clinical research study to address gaps in the Australian context

Critical research questions that should be addressed by Australian CT screening projects include:

  1. Is population based CT screening cost-effective in Australia?
  2. How best to implement safe and effective population based CT screening in Australia?

Key implementation issues

  1. How will eligible ever-smokers be approached and recruited into a screening program in a way that maximises uptake from eligible individuals, yet minimises distress and/or screening demand from lower-risk screening-ineligible individuals?
  2. How can access to screening with appropriate low-dose CT technology be provided to those living in rural and remote Australia?
  3. How can quality and consistency in eligibility assessment, screening adherence, CT dosimetry and nodule management be implemented?
  4. How should incidental findings be reported? How will such incidental findings be communicated to participants and general practitioners?


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References

  1. 1.0 1.1 1.2 1.3 Aberle DR, Adams AM, Berg CD, Black WC, Clapp JD, Fagerstrom RM, et al. Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med 2011 Aug 4;365(5):395-409 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/21714641.
  2. 2.0 2.1 2.2 Fu C, Liu Z, Zhu F, Li S, Jiang L. A meta-analysis: Is low-dose computed tomography a superior method for risky lung cancers screening population? Clin Respir J 2014 Oct 13 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/25307063.
  3. Saghir Z, Dirksen A, Ashraf H, Bach KS, Brodersen J, Clementsen PF, et al. CT screening for lung cancer brings forward early disease. The randomised Danish Lung Cancer Screening Trial: status after five annual screening rounds with low-dose CT. Thorax 2012 Apr;67(4):296-301 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/22286927.
  4. Wille MM, Dirksen A, Ashraf H, Saghir Z, Bach KS, Brodersen J, et al. Results of the Randomized Danish Lung Cancer Screening Trial with Focus on High-risk Profiling. Am J Respir Crit Care Med 2015 Oct 20 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/26485620.
  5. Infante M, Cavuto S, Lutman FR, Brambilla G, Chiesa G, Ceresoli G, et al. A randomized study of lung cancer screening with spiral computed tomography: three-year results from the DANTE trial. Am J Respir Crit Care Med 2009 Sep 1;180(5):445-53 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/19520905.
  6. Infante M, Cavuto S, Lutman FR, Passera E, Chiarenza M, Chiesa G, et al. Long-term Follow-up Results of the DANTE Trial, a Randomized Study of Lung Cancer Screening with Spiral Computed Tomography. Am J Respir Crit Care Med 2015 Mar 11 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/25760561.
  7. Pastorino U, Rossi M, Rosato V, Marchianò A, Sverzellati N, Morosi C, et al. Annual or biennial CT screening versus observation in heavy smokers: 5-year results of the MILD trial. Eur J Cancer Prev 2012 May;21(3):308-15 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/22465911.
  8. Bach PB, Mirkin JN, Oliver TK, Azzoli CG, Berry DA, Brawley OW, et al. Benefits and harms of CT screening for lung cancer: a systematic review. JAMA 2012 Jun 13;307(22):2418-29 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/22610500.
  9. Humphrey LL, Deffebach M, Pappas M, Baumann C, Artis K, Mitchell JP, et al. Screening for lung cancer with low-dose computed tomography: a systematic review to update the US Preventive services task force recommendation. Ann Intern Med 2013 Sep 17;159(6):411-20 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/23897166.

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Appendices


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