Benchmarking lung cancer screening programmes with adaptive screening frequency against the optimal screening schedules derived from the ENGAGE framework: a comparative microsimulation study

Abstract

Background: Lung cancer screening recommendations employ annual frequency for eligible individuals, despite evidence that it may not be universally optimal. The impact of imposing a structure on the screening frequency remains unknown. The ENGAGE framework, a validated framework that offers fully dynamic, analytically optimal, personalised lung cancer screening recommendations, could be used to assess the impact of screening structure on the effectiveness and efficiency of lung cancer screening.

Methods: In this comparative microsimulation study, we benchmarked alternative clinically relevant structured lung cancer screening programmes employing a fixed (annual or biennial) or adaptive (start with annual/biennial screening and then switch to biennial/annual at ages 60- or 65-years) screening frequency, against the ENGAGE framework. Individuals were eligible for screening according to the 2021 US Preventive Services Task Force recommendation on lung cancer screening. We assessed programmes' efficiency based on the number of screenings per death avoided (LDCT/DA) and the number of screenings per ever-screened individual (LDCT/ESI), and programmes' effectiveness using quality-adjusted life years (QALY) gained from screening, lung cancer-specific mortality reduction (MR), and number of screen-detected lung cancer cases. We used validated natural history, smoking history generator, and risk prediction models to inform our analysis. Sensitivity analysis of key inputs was conducted.

Findings: ENGAGE was the best performing strategy. Among the structured policies, adaptive biennial-to-annual at age 65 was the best strategy requiring 24% less LDCT/DA and 60% less LDCT/ESI compared to TF2021, but yielded 105 more deaths per 100,000 screen-eligible individuals (10.2% vs. 11.8% MR for TF2021, p = 0.28). Fixed annual screening was the most effective strategy but the least efficient and was ranked as the fifth best strategy. All strategies yielded similar QALYs gained. Adherence levels did not affect the rankings.

Interpretation: Adaptive lung cancer screening strategies that start with biennial and switch to annual screening at a prespecified age perform well and warrant further consideration, especially in settings with limited availability of CT scanners and radiologists.

Funding: National Cancer Institute.

Keywords: Adaptive screening; ENGAGE; Early detection; Low-dose CT; Lung cancer screening.

Fig. 1

Frontiers for current smokers are categorised into moderate smokers: (a) MR vs. LDCT/DA; (b) MR vs. LDCT/ESI; (c) SDC vs. LDCT/DA; (d) SDC vs. LDCT/ESI; and heavy smokers: (e)–(h) analogously. Strategies on each frontier are presented with bold text in the legend. Results are aggregated across the two sexes using the weights presented in Supplemental Table S1. The shaded region indicates the variability in the performance of the ENGAGE-derived screening strategy under different levels of the disutility values associated with false-positive results and regular LDCT exams. Note that, ENGAGE is the only screening strategy that is adaptive to the disutility levels whereas, the performance of the structured strategies is not affected by the disutility values, but their relative position to the frontier may change. MR: Mortality reduction; SDC: Screen-detected early-stage lung cancer cases; LDCT/ESI: Number of screenings per ever-screened individuals; LDCT/DA: Number of screenings per death avoided. TF2021: the 2021 US Preventive Services Task Force lung cancer screening recommendation; A60B (A65B): annual screenings until age of 60 (65) followed by biennial screenings thereafter; B60A (B65A): biennial screenings until age of 60 (65) followed by annual screenings thereafter. Note 1: For this analysis we only considered former smokers who start smoking at age 18 years.

Fig. 2

Frontiers for former smokers are categorised into moderate smokers: (a) MR vs. LDCT/DA; (b) MR vs. LDCT/ESI; (c) SDC vs. LDCT/DA; (d) SDC vs. LDCT/ESI; and heavy smokers: (e)–(h) analogously. Strategies on each frontier are presented with bold text in the legend. Results are aggregated across the two sexes using the weights presented in Supplemental Table S1. The shaded region indicates the variability in the performance of the ENGAGE-derived screening strategy under different levels of the disutility values associated with false-positive results and regular LDCT exams. Note that, ENGAGE is the only screening strategy that is adaptive to the disutility levels whereas, the performance of the structured strategies is not affected by the disutility values, but their relative position to the frontier may change. MR: Mortality reduction; SDC: Screen-detected early-stage lung cancer cases; LDCT/ESI: Number of screenings per ever-screened individuals; LDCT/DA: Number of screenings per death avoided. TF2021: the 2021 US Preventive Services Task Force lung cancer screening recommendation; A60B (A65B): annual screenings until age of 60 (65) followed by biennial screenings thereafter; B60A (B65A): biennial screenings until age of 60 (65) followed by annual screenings thereafter. Note 1: For this analysis we only considered former smokers who start smoking at age 18 years and stop smoking at age 45 years. Note 2: Note that TF2021 and annual-to-biennial strategies are identical for former smokers considered in this study as those individuals become ineligible for screening after age 60 since they complete 15 years since smoking cessation. Similarly, biennial and biennial-to-annual screenings are equivalent for former smokers.

Fig. 3

Total relative (percentages of) gains in effectiveness and efficiency for each strategy compared to the 2021 US Preventive Services Task Force lung cancer screening recommendation using the weighted sum of individual relative gains over all smoking groups and sexes. Negative values indicate loss of effectiveness or efficiency. Supplementary Methods (2) further details the computations. TF2021: the 2021 US Preventive Services Task Force lung cancer screening recommendation; A60B (A65B): annual screenings until age of 60 (65) followed by biennial screenings thereafter; B60A (B65A): biennial screenings until age of 60 (65) followed by annual screenings thereafter.