Brief Report: Impact of joint lung cancer screening and cessation interventions under the new USPSTF recommendations

Abstract

Background

In 2021, the USPSTF revised its lung cancer screening recommendations expanding its eligibility. As more smokers become eligible, cessation interventions at the point of screening could enhance the benefits. Here we assess the effects of joint screening and cessation interventions under the new recommendations.

Methods.

A validated lung cancer natural history model was used to estimate lifetime number of low-dose computed tomography (LDCT) screens, percentage ever screened, lung cancer deaths, lung cancer deaths averted and life-years gained for the 1960 US birth cohort aged 45 through 90 years (4.5 million individuals). Screening occurred according to USPSTF 2013 and 2021 recommendations with varying uptake (0%, 30%, 100%), with or without a cessation intervention at the point of screening with varying effectiveness (15%, 100%).

Results:

Screening 30% of the eligible population according to 2021 criteria with no cessation intervention (USPSTF2021/30%_uptake/without_cessation) was estimated to result in 6,845 lung cancer deaths averted and 103,725 life-years gained. These represent 28% and 34% increases, respectively, relative to screening according to 2013 guidelines (USPSTF2013/30%/without). Adding a cessation intervention at the time of the first screen with 15% effectiveness (USPSTF2021/30%/with_15%) was estimated to result in 2,422 additional lung cancer deaths averted (9,267 total, ~73% increase vs USPSTF2013/30%/without) and 322,785 life-years gained (~318% increase). Screening 100% of the eligible according to 2021 guidelines with no cessation intervention (USPSTF2021/100%/without) was estimated to result in 23,444 lung cancer deaths averted (~337% increase vs USPSTF2013/30%/without) and 354,330 life-years gained (~359% increase). Adding a cessation intervention with 15% effectiveness (USPSTF2021/100%/with_15%) would result in 31,998 lung cancer deaths averted (~497% increase vs USPSTF2013/30%/without) and 1,086,840 life-years gained (~1,309% increase).

Conclusions:

Joint screening and cessation interventions would result in considerable lung cancer deaths averted and life-years gained. Adding a one-time cessation intervention of modest effectiveness (15%) results in comparable life-years gained as increasing screening uptake from 30% to 100% because while cessation decreases mortality from many causes, screening only reduces lung cancer mortality. This simulation indicates that incorporating cessation programs into screening practice should be a priority as it can maximize overall benefits.

Introduction

The US Preventive Services Task Force (USPSTF) recently updated its 2013 lung cancer screening recommendations expanding its eligibility criteria.¹ Annual lung cancer screening with low-dose computed tomography (LDCT) is now recommended for adults aged 50 through 80 years who have a smoking history of at least 20 pack-years and currently smoke or have quit within the past 15 years. This expands eligibility to individuals of younger ages (50 vs 55 ages) and lower smoking exposures (20 vs 30 pack-years).

Since 2013, the USPSTF recommends that current smokers undergoing screening should receive smoking cessation interventions.¹ Cessation interventions at the point of screening have the potential to enhance the benefits of LDCT screening resulting in additional premature deaths averted and life-years gained.^2–4 The expansion of the eligibility criteria to include younger smokers with fewer pack-years has the potential to expand these additional benefits. Here we quantify the potential impact.

Methods

We used a validated natural history model (MichiganLung) to assess the impact of joint LDCT screening and cessation interventions on lung cancer and overall mortality. It was one of four models commissioned by the USPSTF to evaluate the benefits and harms of LDCT screening.⁵

Model Description

MichiganLung is a microsimulation model that uses individual smoking histories, including those of adults in the expanded eligibility groups, to simulate the natural history of lung cancer (onset, histological type, stage progression, clinical detection and mortality or survival), the outcomes from LDCT screening and any resulting follow-up and treatment intervention, and non-lung cancer related deaths based.^5,6 The model uses a dose-response module to estimate annual age-specific lung cancer incidence as a function of individual smoking history, sex, and birth year.^3,5,7,8 The model has been used to simulate the impact of screening for the US population,^5,9,10 as well as the effectiveness and cost-effectiveness of cessation interventions at the point of screening under the 2013 USPSTF criteria.^3,7

Interventions

We used MichiganLung to simulate the impact of screening with or without a one-time cessation intervention at the first screening. We simulated screening according to the 2021 and 2013 USPSTF recommendations and compared the results with a no screening scenario. We assumed two main screening random uptake scenarios: 30% and 100% of those eligible to actually participate in annual screening. We also considered 70% uptake in a sensitivity analysis. Every current smoker undergoing LDCT screening was assumed to receive the smoking cessation intervention. We considered two main cessation effectiveness scenarios (i.e. probability of permanently quitting due to the intervention); 15% (realistic)⁴ and 100% (maximal)¹¹ probability of quitting. We also considered 7% and 30% probabilities of quitting as sensitivity analysis. While there are few trials published to date on cessation interventions in the lung cancer screening setting, these values (7–30% range) are consistent with early studies.^3,4,7

Population and Outcomes

Consistent with previous work, we simulated outcomes for the 1960 US birth cohort. We focus on this birth-cohort as it is currently in the middle of its screening eligibility and is representative of the smoking patterns of the current screen-eligible population. We simulated the smoking histories of one million males and one million females using the CISNET Smoking History generator,^3,8 and then used MichiganLung under different screening and cessation scenarios. In particular, we estimated the lifetime number of LDCT screens, percentage of the population ever screened, lung cancer deaths, lung cancer deaths averted, life-years and life-years gained. While deaths averted are lung cancer-specific, life-years gained represent all tobacco-related causes of death. Outcomes are scaled to the 1960 US birth cohort population (~4.5 million at age 45).

Results

Under USPSTF 2021 guidelines, 23% of the individuals from the 1960 US birth cohort would be eligible for screening, a 60% increase over the 2013 guidelines (Table 1). Of these, 77% would enter screening eligibility as current smokers and thus would be eligible for a cessation intervention at the time of their first screen (Figure 1).

Table 1.

Projected lifetime^a impact of screening and cessation interventions for the 4.5 million individuals from the US 1960 birth cohort

Screening criteria	Screening uptakee (% of eligible getting screened)	Cessation intervention effectivenesse (probability of permanently quitting)	% of total population screened	Number of LDCT screensb	Lung cancer deaths	Lung cancer deaths avertedc	Percentage increase in lung cancer deaths averted vs 2013 USPSTF scenario with no cessation intervention	Life-years	Life-years gainedc	Percentage increase in life-years gained vs 2013 USPSTF scenario with no cessation intervention	Percentage of life-years gained due to lung cancer deaths averted or delayedd
No screening	NA	NA	0%	NA	178,130	NA	NA	168,908,310	NA	NA	NA
2013 USPSTF	30%	Without	4.3%	3,112,261	172,766	5,363	Reference Group	168,985,440	77,130	Reference Group	100%
	30%	15%	4.3%	2,979,788	171,170	6,960	30%	169,108,380	200,070	159%	51%
	30%	100%	4.3%	2,298,585	161,581	16,549	209%	169,795,620	887,310	1050%	27%
	100%	Without	14.3%	10,348,862	160,313	17,816	232%	169,167,555	259,245	236%	100%
	100%	15%	14.3%	9,946,827	154,523	23,607	340%	169,572,465	664,155	761%	51%
	100%	100%	14.3%	7,640,316	123,077	55,053	926%	171,869,355	2,961,045	3739%	27%
2021 USPSTF	30%	Without	6.9%	5,725,895	171,285	6,845	28%	169,012,035	103,725	34%	100%
	30%	15%	6.9%	5,352,831	168,863	9,267	73%	169,231,095	322,785	318%	44%
	30%	100%	6.9%	3,249,802	154,579	23,551	339%	170,473,275	1,564,965	1929%	22%
	100%	Without	23.0%	19,141,776	154,686	23,444	337%	169,262,640	354,330	359%	100%
	100%	15%	23.0%	17,884,769	146,132	31,998	497%	169,995,150	1,086,840	1309%	44%
	100%	100%	23.0%	10,807,812	99,958	78,172	1357%	174,092,310	5,184,000	6621%	23%

^aFrom age 45 to 90

^bNumber of LDCT screens decreases in the scenarios with cessation intervention since former smokers exit screening after 15 years since quitting

^cNumber of lung cancer deaths averted and life-years gained compared to the no screening scenario

^dPercentage of the life-years gained in the scenario due to lung cancer deaths averted or delayed by screening or by smoking cessation due to the intervention. The complement is the percentage of the life-years gained due to averted premature deaths from all other smoking-related causes by cessation due to the intervention

^eResults for additional scenarios are shown in the supplementary material

Figure 1.

Age-specific screening eligibility of individuals from the 1960 US birth-cohort according to 2013 USPSTF guidelines (left) or 2021 USPSTF guidelines (right). The different shaded areas represent the proportion of the cohort eligible and not eligible for screening by smoking status. The darkest area at the bottom represents the percentage of the cohort eligible for joint screening and cessation interventions.

Relative to 2013 guidelines, screening according to USPSTF 2021 is estimated to result in considerable gains, particularly when combined with cessation interventions (Table 1 and Figure 2). For example, screening 30% of the eligible population born in 1960 according to 2013 recommendations with no cessation intervention (USPSTF2013/30%_uptake/without_cessation) was estimated to result in 5,363 lung cancer deaths averted and 77,130 life-years gained relative to no-screening. Screening 30% of the eligible population according to 2021 recommendations with no cessation intervention (USPSTF2021/30%/without) was estimated to result in 6,845 lung cancer deaths averted (~28% increase vs USPSTF2013/30%/without) and 103,725 life-years gained (~34% increase). Adding a cessation intervention at the time of the first screen with a 15% effectiveness (USPSTF2021/30%/with_15%) would result in 2,422 additional lung cancer deaths averted (9,267 in total, ~73% increase vs USPSTF2013/30%/without) and in a total of 322,785 life-years gained (~318% increase). Screening 100% of the eligible individuals with no cessation intervention (USPSTF2021/100%/without) was estimated to result in 23,444 lung cancer deaths averted (~337% increase vs USPSTF2013/30%/without) and 354,330 life-years gain (~359% increase). Adding a cessation intervention at the time of the first screen with a 15% effectiveness (USPSTF2021/100%/with_15%) would result in 8,554 additional lung cancer deaths averted (31,998 in total, ~497% increase vs USPSTF2013/30%/without) and in a total of 1,086,840 life-years gained (~1,309% increase). Table 1 and Figure 2 show the maximum lung cancer deaths averted and life-years gained with a cessation intervention with 100% quit probability (Maximal Potential Reduction in Premature Mortality¹¹).

Figure 2.

Cumulative life-years gained (top) and cumulative lung cancer deaths averted (bottom) of joint screening and cessation interventions for the 4.5 million individuals at age 45 from the US 1960 birth cohort under different screening uptake and cessation intervention effectiveness assumptions. Left panels correspond to LDCT screening under the USPSTF 2013 guidelines and right panels to screening under the USPSTF 2021 guidelines.

Sensitivity analyses with scenarios assuming 7% or 30% as probability of quitting are presented in the supplementary content (Table S1). These show the range of potential health gains as a function of the effectiveness of the cessation intervention. Even with cessation interventions of limited effectiveness (7%), joint cessation and screening interventions could result in considerable increases in lung cancer deaths averted and life-years gained. For example, screening 30% of the eligible population according to USPSTF 2021 with a one-time cessation intervention with a 7% effectiveness would result in 50% more lung cancer deaths averted and 161% more life-years gained than screening 30% of the eligible population according to the 2013 recommendations with no cessation intervention.

Discussion

Consistent with other studies,^3,7,12–14 the analysis indicates that joint LDCT screening and cessation interventions could result in important reductions in lung cancer and overall tobacco related premature mortality. In particular, by expanding the number of smokers eligible for screening to include younger smokers with fewer pack-years, many of whom are projected to be women and racial/ethnic minorities,⁵ the 2021 USPSTF recommendations could result in more life-years gained than previous criteria and be more equitable.

Previous studies have projected the potential impact of cessation interventions at the point of LDCT screening under previous screening guidelines,^3,7,12–14 or the benefits and harms of expanding screening to individuals with 20 or more pack-years of smoking history, but without consideration of joint screening cessation interventions.⁵ Here we extend previous studies by quantifying the potential impact of screening according to the 2021 USPSTF recommendations with joint cessation interventions.

The actual impact of these interventions will depend on screening uptake, overall and as a function of risk characteristics, the actual percentage of current smokers in the screened population, and the effectiveness and adoption of the specific cessation interventions. Furthermore, the impact might increase when engaging continuing smokers in cessation interventions at each successive screening visit. While screening uptake has been relatively low, the percentage of eligible individuals receiving screening appeared to be increasing prior to the COVID-19 pandemic.¹⁵ The 30% uptake used as baseline assumption in the simulations should be reachable in the next few years given the increasing uptake rates and the reported levels prior to the pandemic (~20% in 2018¹⁵). The efficacy of cessation interventions at the point of screening is being evaluated in several randomized controlled trials.² While awaiting these results, this simulation analysis shows that even under conservative assumptions, adding a one-time cessation intervention at the baseline screen with modest effectiveness could result in considerable gains versus screening alone, especially in life-years gained from a reduction in all tobacco-related causes of death. Importantly, adding a cessation intervention with 15% effectiveness is estimated to result in similar increases in life-years gained as increasing screening uptake from 30% to 100% without cessation interventions. This is because a considerable percentage of the eligible population are current smokers and because cessation interventions decrease mortality for many causes of death, while screening only lowers lung cancer mortality. This indicates that incorporating cessation programs into screening practice, together with efforts to increase the success of these programs, should be a priority to maximize the overall benefits.

Conclusions

LDCT screening, according to the new USPSTF guidelines, combined with joint cessation interventions, would result in considerable lung cancer deaths averted and life-years gained. In terms of life-years gained, adding a cessation intervention of modest effectiveness to LDCT screening results in comparable gains as increasing screening uptake from 30% to 100%. Both screening and cessation interventions are critical for lung cancer prevention; joint screening and cessation programs for those eligible would maximize health benefits.