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Systematic review
Lung cancer screening with low-dose CT: benefits and potential risks
  1. Nichole T Tanner,
  2. Gerard A Silvestri
  1. Department of Medicine, Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, 96 Jonathan Lucas Street, CSB Suite 812, Charleston, SC 29425, USA
  1. Correspondence to : Dr Nichole T Tanner
    Medical Univestity of South Carolina, Charleston, SC 29425, USA; tripici{at}musc.edu

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Context

Lung cancer is the leading cause of cancer death worldwide.1 The majority of patients present with advanced disease and the current 5-year survival is only 15%.2 Previous research showed no mortality benefit to screening with chest radiography and sputum cytology. The recent results of the National Lung Screening Trial (NLST) are the first to show a significant reduction in lung cancer mortality with the use of low-dose CT (LDCT) in high risk individuals. The potential for harm with screening and generalisability of results have been a cause for concern in initiation of lung cancer screening programmes. As such, a multisociety collaborative initiative was undertaken to develop the foundation for a clinical guideline for lung cancer screening.

Methods

The authors performed a literature search using MEDLINE, EMBASE and the Cochrane Library databases to identify randomised controlled trials (RCTs) using LDCT screening for lung cancer or non-comparative cohort studies of LDCT screening. The inclusion criteria required that the identified studies reported on at least one specified outcome. Only data from RCTs were considered eligible for inclusion for lung cancer-specific and all-cause mortality end points. Studies that only evaluated screening in those with risk factors other than smoking, those not published in English and meta-analyses or case-series of outcomes limited to those diagnosed with lung cancer were excluded. A systematic review was performed independently by two reviewers. A third reviewer verified articles deemed ineligible and reviewed any citations in which there was a discrepancy.

Findings

The authors identified 21 studies meeting their inclusion criteria (8 RCTs and 13 cohort studies). The potential benefits of screening with LDCT identified were the effect on mortality and the effect on smoking behaviour. Their review produced three RCTs from which lung-cancer specific mortality and all-cause mortality inferences could be drawn. The largest of these studies (53 454 enrolled) and the only to find a difference in lung cancer (0.3% absolute risk reduction, 20% relative risk reduction) and all-cause mortality (6.7% relative risk reduction) in favour of screening was the NLST though some trials are not complete. The authors calculated that 310 individuals would need to undergo screening for three rounds to prevent one lung cancer death. The review found no evidence that smoking cessation or recidivism is meaningfully reduced by participation in a screening programme.

The potential harms of LDCT screening considered in the review included the detection of abnormalities, complications of diagnostic procedures, overdiagnosis, radiation exposure and quality of life. The average nodule detection rate was 30%, but ranged from 3% to 30% in RCTs and 5% to 51% in cohort studies; the majority of studies reported that more than 90% of nodules were benign and most often triggered further imaging. The NLST was the only study included in the review that reported on screening complications. The frequency of major complications occurring during a diagnostic evaluation of a screen detected abnormality was 33 per 10 000 individuals screened by LDCT. The overdiagnosis rate for LDCT could not be estimated. Based on their review and use of data from the NLST, the authors estimate approximately one cancer death may be caused by radiation from imaging per 2500 persons screened though these estimates are likely imprecise. Finally, the authors concluded that the effect of LDCT screening on quality of life was uncertain based on the one study identified that reported on this metric.

Commentary

The authors present a systematic review of the potential harms and benefits of LDCT for screening of lung cancer. This review, conducted by a multisociety group, is the first of its kind to include the results of the NLST trial, the largest RCT for use of LDCT screening for lung cancer in high risk individuals to date and is the basis for a clinical practice guideline for lung cancer screening.

Overall, this review has sound methodology making it unlikely that relevant studies were missed. The authors do an exceptional job of presenting a well-balanced analysis of the benefits and potential harms of lung cancer screening with LDCT. They conclude that there is a reasonable amount of data to recommend LDCT screening in smokers and former smokers who meet the inclusion criteria for the NLST, but only in settings that can provide comprehensive care and after the patient has been counseled on the potential benefits and harms. The literature also supports that LDCT screening can lead to harm as additional imaging leads to an increased radiation exposure and interventional procedures performed for benign disease.

The review raises concerns that are not addressed including the generalisability of the results, the barriers to large-scale implementation and screening adherence. Another question is whether to allocate limited healthcare resources to screening for lung cancer as opposed to funding programmes that both reduce initiation of smoking and increase smoking cessation with benefits beyond reductions of lung cancer mortality.

References

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Footnotes

  • Competing interests None.

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