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

Abstract

Background Diagnosis of lung cancer frequently occurs in its later stages. Low-dose computed tomography (LDCT) could detect lung cancer early. Objectives To estimate the effectiveness and cost-effectiveness of LDCT lung cancer screening in high risk populations. Methods Clinical effectiveness A systematic review of randomised controlled trials (RCTs) comparing LDCT screening programmes with usual care (no screening) or other imaging screening programme (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 twelve different population eligibility criteria and four intervention frequencies (single screen, triple screen, annual screening and biennial screening) and a no screening control arm. Results Clinical effectiveness Twelve RCTs were included, four of which currently contribute evidence on mortality. Meta-analysis of these demonstrated that LDCT with up to 9.80 years of follow-up was associated with a non-statistically significant decrease in lung cancer mortality (pooled RR 0.94, 95% CI 0.74 to 1.19). The findings also showed that LDCT screening demonstrated a non-statistically significant increasein 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 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 with usual care intermediate. 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/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 a minority of analyses. Limitations Clinical 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. Conclusions LDCT 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 work Effectiveness and cost-effectiveness estimates should be updated with the anticipated results from several ongoing RCTs (particularly NELSON).