Time to Benefit for Lung Cancer Screening: A Systematic Review and Survival Meta-Analysis

Abstract

Introduction: Lung cancer screening with low-dose computed tomography reduces lung cancer mortality in the long term but carries immediate risks. Guidelines recommend screening persons whose life expectancy exceeds the screening test's time to benefit, defined as the time from screening initiation to first observed benefit. This study aimed to estimate the time to benefit for lung cancer screening to prevent lung cancer mortality.

Methods: Randomized controlled trials of lung cancer screening with low-dose computed tomography were identified from two prior systematic reviews and an updated search to December 3, 2023. Studies that reported lung cancer mortality were included. For each study, independent Weibull survival curves were fitted and Markov chain Monte Carlo simulations were generated to estimate the absolute risk reduction at different time points. Time to benefit was determined as the time at which absolute risk reduction thresholds (ARR=0.0005, 0.001, 0.002) were crossed. These estimates were pooled using a random-effects meta-analysis model.

Results: A total of eight randomized controlled trials comprising 88,526 participants were included. Enrollment age ranged from age 50 to 70 years; follow-up duration ranged from 7.3 to 12.3 years. For every 1,000 persons screened, 3.4 years (95%=CI 2.2, 5.1) passed before 1 death from lung cancer was prevented (ARR=0.001). The time to prevent one lung cancer death per 2,000 persons screened (ARR=0.0005) was 2.2 years (95% CI=1.4, 3.4); per 500 persons screened (ARR=0.002), it was 5.2 years (95%=CI 3.7, 7.3).

Discussion: Lung cancer screening is most appropriate for older adults at high risk of lung cancer with a life expectancy greater than 3.4 years.

Appendix Figure 1.

Comparison between Weibull survival curves and Kaplan-Meier curves for lung cancer mortality in control and intervention groups.

Appendix Figure 2.. Comparison between Weibull survival curves and Kaplan-Meier curves for all-cause mortality in control and intervention groups.

The UKLS trial by Field et al. was not included as it did not report all-cause mortality for all participants.

Appendix Figure 3.. Time to benefit for lung cancer screening to prevent lung cancer death at an absolute risk reduction of 0.0005.

NLST results were derived using individual data from the original dataset. The upper limit of 95% confidence interval does not exceed 12.0 years due to censoring at 12 years of follow-up.

Appendix Figure 4.. Time to benefit for lung cancer screening to prevent lung cancer death at an absolute risk reduction of 0.002.

NLST results were derived using individual data from the original dataset. The upper limit of 95% confidence interval does not exceed 12.0 years due to censoring at 12 years of follow-up.

Appendix Figure 5.. Time to benefit for lung cancer screening to prevent all-cause mortality at an absolute risk reduction of 0.001.

NLST results were derived using individual data from the original dataset. The upper limit of 95% confidence interval does not exceed 12.0 years due to censoring at 12 years of follow-up. The UKLS trial by Field et al. was not included as it did not report all-cause mortality for all participants required for the time-to-benefit analysis.

Appendix Figure 6.. Time to benefit for lung cancer screening to prevent all-cause mortality at an absolute risk reduction of 0.0005.

NLST results were derived using individual data from the original dataset. The upper limit of 95% confidence interval does not exceed 12.0 years due to censoring at 12 years of follow-up. The UKLS trial by Field et al. was not included as it did not report all-cause mortality for all participants required for the time-to-benefit analysis.

Appendix Figure 7.. Time to benefit for lung cancer screening to prevent all-cause mortality at an absolute risk reduction of 0.002.

NLST results were derived using individual data from the original dataset. The upper limit of 95% confidence interval does not exceed 12.0 years due to censoring at 12 years of follow-up. The UKLS trial by Field et al. was not included as it did not report all-cause mortality for all participants required for the time-to-benefit analysis.

Appendix Figure 8.. Absolute risk reduction in all-cause mortality after lung cancer screening over time.

Shaded areas and parenthesized numbers represent 95% confidence intervals.

Figure 1.

PRISMA study selection flow diagram. *Bonney et al. and Field et al.

Figure 2.

Time to benefit in years for lung cancer screening to prevent lung cancer death at an absolute risk reduction of 0.001. NLST results were derived using individual data from the original dataset. The upper limit of 95% CI does not exceed 12.0 years due to censoring at 12 years of follow-up.

Figure 3.

Absolute risk reduction in lung cancer mortality after lung cancer screening over time across 8 RCTs. Shaded areas and parenthesized numbers represent 95% CIs.