Low-dose computed tomography for lung cancer screening in high-risk populations: a systematic review and economic evaluation

Abstract

BackgroundDiagnosis of lung cancer frequently occurs in its later stages. Low-dose computed tomography (LDCT) could detect lung cancer early.ObjectivesTo estimate the clinical effectiveness and cost-effectiveness of LDCT lung cancer screening in high-risk populations.Data sourcesBibliographic sources included MEDLINE, EMBASE, Web of Science and The Cochrane Library.MethodsClinical effectiveness – a systematic review of randomised controlled trials (RCTs) comparing LDCT screening programmes with usual care (no screening) or other imaging screening programmes [such as chest X-ray (CXR)] was conducted. Bibliographic sources included MEDLINE, EMBASE, Web of Science and The Cochrane Library. Meta-analyses, including network meta-analyses, were performed. Cost-effectiveness – an independent economic model employing discrete event simulation and using a natural history model calibrated to results from a large RCT was developed. There were 12 different population eligibility criteria and four intervention frequencies [(1) single screen, (2) triple screen, (3) annual screening and (4) biennial screening] and a no-screening control arm.ResultsClinical effectiveness – 12 RCTs were included, four of which currently contribute evidence on mortality. Meta-analysis of these demonstrated that LDCT, with ≤ 9.80 years of follow-up, was associated with a non-statistically significant decrease in lung cancer mortality (pooled relative risk 0.94, 95% confidence interval 0.74 to 1.19). The findings also showed that LDCT screening demonstrated a non-statistically significant increase in all-cause mortality. Given the considerable heterogeneity detected between studies for both outcomes, the results should be treated with caution. Network meta-analysis, including six RCTs, was performed to assess the relative clinical effectiveness of LDCT, CXR and usual care. The results showed that LDCT was ranked as the best screening strategy in terms of lung cancer mortality reduction. CXR had a 99.7% probability of being the worst intervention and usual care was ranked second. Cost-effectiveness – screening programmes are predicted to be more effective than no screening, reduce lung cancer mortality and result in more lung cancer diagnoses. Screening programmes also increase costs. Screening for lung cancer is unlikely to be cost-effective at a threshold of £20,000/quality-adjusted life-year (QALY), but may be cost-effective at a threshold of £30,000/QALY. The incremental cost-effectiveness ratio for a single screen in smokers aged 60–75 years with at least a 3% risk of lung cancer is £28,169 per QALY. Sensitivity and scenario analyses were conducted. Screening was only cost-effective at a threshold of £20,000/QALY in only a minority of analyses.LimitationsClinical effectiveness – the largest of the included RCTs compared LDCT with CXR screening rather than no screening. Cost-effectiveness – a representative cost to the NHS of lung cancer has not been recently estimated according to key variables such as stage at diagnosis. Certain costs associated with running a screening programme have not been included.ConclusionsLDCT screening may be clinically effective in reducing lung cancer mortality, but there is considerable uncertainty. There is evidence that a single round of screening could be considered cost-effective at conventional thresholds, but there is significant uncertainty about the effect on costs and the magnitude of benefits.Future workClinical effectiveness and cost-effectiveness estimates should be updated with the anticipated results from several ongoing RCTs [particularly the NEderlands Leuvens Longkanker Screenings ONderzoek (NELSON) screening trial].Study registrationThis study is registered as PROSPERO CRD42016048530.FundingThe National Institute for Health Research Health Technology Assessment programme.

Benefits, harms and cost-effectiveness of cancer screening in Australia: an overview of modelling estimates

“…35 A review of this and other trials has shown considerable variation in outcomes relevant to the balance of benefits, harms and cost-effectiveness, such as screening rates, false-positive rates and lung cancer detection rates, all of which are sensitive to the screening regimen and target population. 54 The recently commenced International Lung Screen Trial in Australia and Canada 55 will provide essential information on screening a high-risk Australian cohort, and aid in identifying an acceptable cost-effective screening program in Australia.…”

Recommendations for Implementing Lung Cancer Screening with Low-Dose Computed Tomography in Europe

“…In recent years, a series of CEAs for European countries have been published: in Germany, two studies found an incremental cost-effectiveness ratio (ICER) of €19,302 per life year (LY) gained (€30,241 per QALY) and €16,754-23,847 per LY [172,173]; in the UK, two studies found an ICER lower than £11,000 per QALY [39,174], whereas the most recent study found an ICER between £20,000 and £30,000 per QALY, but under extreme assumptions, such as very small cost advantage in treating Stages I and IV and no increase in average survival between the screening and no-screening scenarios [175]; in Poland, an ICER of €1353 per LY gained was found [176]. For Italy, our simulation-based model populated with real-world cost data from hospital records found an ICER of €3297 per QALY gained and €2944 per LY gained [177]: note that this is the most recent study in this sense, and it included immunotherapy for the treatment of Stages III and IV.…”

Direct and indirect healthcare costs of lung cancer CT screening in Denmark: a registry study

“…Systematic reviews have found significant heterogeneity in methodology and results of economic evaluations of lung cancer screening 14 15. Several researchers have analysed the cost-effectiveness of CT screening based on the NLST.…”

“…Two recent systematic reviews of cost-effectiveness analyses of Lung Cancer Screening concluded that it is still unclear whether or not low dose CT screening is cost effective 14 15. Several things can influence cost-effectiveness estimates among other: overdiagnosis, lead-time bias, the at-risk population, the characteristics of a smoking cessation programme and incidental findings 14 15. Only one study included incidental findings 15 17…”