Cost-Effectiveness Analysis of Lung Cancer Screening Accounting for the Effect of Indeterminate Findings

Abstract

Background: Numerous health policy organizations recommend lung cancer screening, but no consensus exists on the optimal policy. Moreover, the impact of the Lung CT screening reporting and data system guidelines to manage small pulmonary nodules of unknown significance (a.k.a. indeterminate nodules) on the cost-effectiveness of lung cancer screening is not well established.

Methods: We assess the cost-effectiveness of 199 screening strategies that vary in terms of age and smoking eligibility criteria, using a microsimulation model. We simulate lung cancer-related events throughout the lifetime of US-representative current and former smokers. We conduct sensitivity analyses to test key model inputs and assumptions.

Results: The cost-effectiveness efficiency frontier consists of both annual and biennial screening strategies. Current guidelines are not on the frontier. Assuming 4% disutility associated with indeterminate findings, biennial screening for smokers aged 50-70 years with at least 40 pack-years and less than 10 years since smoking cessation is the cost-effective strategy using $100 000 willingness-to-pay threshold yielding the highest health benefit. Among all health utilities, the cost-effectiveness of screening is most sensitive to changes in the disutility of indeterminate findings. As the disutility of indeterminate findings decreases, screening eligibility criteria become less stringent and eventually annual screening for smokers aged 50-70 years with at least 30 pack-years and less than 10 years since smoking cessation is the cost-effective strategy yielding the highest health benefit.

Conclusions: The disutility associated with indeterminate findings impacts the cost-effectiveness of lung cancer screening. Efforts to quantify and better understand the impact of indeterminate findings on the effectiveness and cost-effectiveness of lung cancer screening are warranted.

Figure 1.

Flowchart of key clinical screening events. LDCT = low-dose computed tomography; Lung-RADS = Lung CT screening reporting and data system.

Figure 2.

Cost-effectiveness efficiency frontier of lung cancer screening with low-dose computed tomography in asymptomatic individuals when the disutility associated with indeterminate findings is applied up to the first negative follow-up exam and is equal to A) 0% and B) 4%. X-S-E-P-Q represents efficient screening strategies where X = screening frequency (annual [A] and biennial [B]); S = starting age; E = stopping age; P = pack-years; Q = years since smoking cessation; X-S-E-P-Q* denotes strategies with modified Lung CT screening reporting and data system as their follow-up management for indeterminate findings. CMS = Centers for Medicare & Medicaid Services; ICER = incremental cost-effectiveness ratio; USPSTF = US Preventive Services Task Force.

Figure 3.

Effect of the disutility associated with indeterminate findings. A) Effect of disutility associated with indeterminate findings on the cost-effectiveness efficiency frontier of lung cancer screening in asymptomatic individuals when the disutility associated with indeterminate findings is 4% and applied up to the first negative follow-up exam. The following strategies, given in ascending order of their cost, are forming the efficiency frontiers under each scenario: Lung CT screening reporting and data system (Lung-RADS) Category 2 Only‡: B-60-70-40-10 (cost-effective with $50K/QALY WTP threshold), B-55-69-40-10, B-50-70-40-20, A-50-70-40-10, A-50-70-30-10 (cost-effective with $100K/QALY WTP threshold), A-50-75-20-10, A-50-75-20-15, A-50-75-20-20, A-50-80-20-20; No disutility: B-60-70-40-10, B-55-69-40-10* (cost-effective with $50K/QALY WTP threshold), B-55-69-40-15*, B-50-70-40-10, A-50-70-40-15, A-50-70-30-10 (cost-effective with $100K/QALY WTP threshold), A-50-75-30-15, A-50-75-20-15, A-50-75-20-20, A-50-80-20-20; 1% disutility: B-60-70-40-10, B-55-69-40-10* (cost-effective with $50K/QALY WTP threshold), B-55-69-40-15*, B-50-70-40-10, B-50-70-30-15*, A-50-70-40-15 (cost-effective with $100K/QALY WTP threshold), A-50-70-30-10, A-50-75-30-15, A-50-75-20-15, A-50-75-20-20, A-50-80-20-20; 2% Disutility: B-60-70-40-10 (cost-effective with $50K/QALY WTP threshold), B-55-69-40-10*, B-55-69-40-15*, B-50-70-40-10, B-50-70-30-15* (cost-effective with $100K/QALY WTP threshold), B-50-74-30-10*, A-50-70-30-10, A-50-75-30-15, A-50-75-20-15, A-50-80-20-20; 4% disutility: B-60-70-40-10, B-55-69-40-10*, B-55-69-40-15*, B-50-70-40-10 (cost-effective with $100K/QALY WTP threshold), B-50-74-30-10*, B-50-74-30-15*, A-50-75-30-15, A-50-80-30-20, A-50-80-20-20; 6% disutility: B-60-70-40-10, B-55-69-40-10*, B-55-69-40-15* (cost-effective with $100K/QALY WTP threshold), B-50-70-40-10*, B-50-74-30-10*, B-50-74-30-15*, B-50-80-30-20*, A-50-75-30-15, A-50-80-30-15, A-50-80-30-20; 8% disutility: B-60-70-40-10*, B-55-69-40-10* (cost-effective with $100K/QALY WTP threshold), B-55-69-40-15*, B-55-75-40-15*, B-50-74-30-10*, B-50-74-30-15*, B-50-80-30-20*, A-55-80-30-20, A-50-80-30-20. B) Percentage change in incremental QALYs per person accrued from the efficient strategies comprising the cost-effectiveness efficiency frontier of our base-case analysis with the disutility associated with indeterminate findings set at 4% (baseline represents the QALYs accrued when the disutility level associated with indeterminate findings is set at 4%) under various levels of the disutility associated with indeterminate findings and the Lung-RADS Category 2 Only follow-up management ([QALY of screening strategy tested – QALY of base-case screening strategy]/QALY of base-case screening strategy). QALYs = quality-adjusted life-years; WTP: willingness-to-pay; X-S-E-P-Q represents efficient screening strategies where X = screening frequency (annual [A] and biennial [B]); S = starting age; E = stopping age; P = pack-years; Q = years since smoking cessation; X-S-E-P-Q* denotes biennial strategies with modified Lung-RADS follow-up management for indeterminate findings. ^‡All indeterminate findings are assessed as Lung-RADS Category 2 findings.

Figure 4.

Sensitivity analysis relative to “No Screening” strategy. Sensitivity analysis of the ICER for A) A-50-70-30-10 strategy (with no disutility associated with indeterminate findings) on changes in health utility inputs, B) A-50-70-30-10 strategy (with no disutility associated with indeterminate findings) on changes in cost inputs, C) B-50-70-40-10 strategy (with 4% disutility associated with indeterminate findings) on changes in health utility inputs, and D) B-50-70-40-10 strategy (with 4% disutility associated with indeterminate findings) on changes in cost inputs, relative to no screening for the US general population born in 1950. Initial phase is defined as the first year after diagnosis; continuing phase is defined as the time after 1 year from diagnosis and 1 year before death; terminal care is provided for the last year of a person’s life; X-S-E-P-Q represents the efficient screening strategy where X = screening frequency (annual [A] and biennial [B]); S = starting age; E = stopping age; P = pack-years; Q = years since smoking cessation. Chemo = chemotherapy; ICER = incremental cost-effectiveness ratio; LDCT = low-dose computed tomography; PET = positron emission tomography; rad = radiation therapy.^‡Unless specified otherwise, the range of the parameter value was defined by plus or minus 20% around their baseline value shown in Table 1.