The meta-analysis [1] of nine trials calculated a 16% reduction in lung cancer (LC) mortality. However, the authors acknowledged that the inclusion of deaths up to 10 years after the last screen dilutes the relative effect of screening, “conservatively biasing the RR [Rate Ratio] … towards unity.”
In the meta-analysis, the 8% reduction in LC mortality in the latest report of the NLST trial had a weight of 0.44. Screening had ended after 2 years, and by 6.5 years of follow-up, 87 LC deaths had been averted (RR 0.80, i.e., 20% reduction) [2]. A re-analysis suggested that the full benefit from the three screens had already been achieved [3]. The updated report [4] confirmed this: 6 further years of follow-up added 791 and 793 further LC deaths in the two arms. So, over the full follow-up, 89 LC deaths were averted, but the RR became 0.92.
Including the additional follow-up, where no benefit is expected, attenuates the rate ratio, but doesn't change the rate difference. The 89 deaths averted by the 3 × 26,000 NLST screens imply 1 death averted per 900 or so screens. A similar calculation, applied to all 9 trials (with 1-10 rounds of screening), yields 162 deaths averted by 154,000 screens, i.e., 1 per 950. The absolute difference in lung cancer deaths is unaffected by the arbitrary numbers of screens and durations of follow-up beyond the period of the screening's effectiveness. Thus, calculations based on it provide a more robust and, we believe, a more appropriate statistical summary.
Author Contribution
All authors contributed equally.
Declaration of Interests
None of the three authors disclosed any relationship/activity/interest that is related to the content of this manuscript.
References
- 1.Field JK, Vulkan D, Davies MPA. Lung cancer mortality reduction by LDCT screening: UKLS randomised trial results and international meta-analysis. The Lancet Regional Health - Europe. 2021 doi: 10.1016/j.lanepe.2021.100184. 00. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Aberle DR, Adams AM, Berg CD, Black WC, Clapp JD, Fagerstrom RM. Reduced lung-cancer mortality with low-dose computed tomographic screening. New Engl J Med. 2011;365:395–409. doi: 10.1056/NEJMoa1102873. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Liu Z (A), Hanley JA, Saarela O, Dendukuri N. A conditional approach to measure mortality reductions due to cancer screening. Int Stat Rev. 2015:1–18. doi: 10.1111/insr.12088. 0, 0. [DOI] [Google Scholar]
- 4.Pinsky P., (for the National Lung Cancer Screening Research Team) Lung cancer incidence and mortality with extended follow-up in the National Lung Screening Trial. J Thorac Oncol. 2019 doi: 10.1016/j.jtho.2019.05.044. Published: June 28. [DOI] [PMC free article] [PubMed] [Google Scholar]
