Cost-Effectiveness of Treatment Thresholds for Subsolid Pulmonary Nodules in CT Lung Cancer Screening.

Background Guidelines such as the Lung CT Screening Reporting and Data System (Lung-RADS) are available for determining when subsolid nodules should be treated within lung cancer screening programs, but they are based on expert opinion. Purpose To evaluate the cost-effectiveness of varying treatment thresholds for subsolid nodules within a lung cancer screening setting by using a simulation model. Materials and Methods A previously developed model simulated 10 million current and former smokers undergoing CT lung cancer screening who were assumed to have a ground-glass nodule (GGN) at baseline. Nodules were allowed to grow and to develop solid components over time according to a monthly cycle and lifetime horizon. Management strategies generated by varying treatment thresholds, including the solid component size and use of the Brock risk calculator, were tested. For each strategy, average U.S. costs and quality-adjusted life years (QALYs) gained per patient were computed, and the incremental cost-effectiveness ratios (ICERs) of those on the efficient frontier were calculated. One-way and probabilistic sensitivity analyses of results were performed by varying several relevant parameters, such as treatment costs or malignancy growth rates. Results Variants of the Lung-RADS guidelines that did not treat pure GGNs were cost-effective. Strategies based on the Brock risk calculator did not reach the efficient frontier. The strategy with the highest QALYs under a willingness-to-pay threshold of $100 000 per QALY included no treatment of GGNs and a threshold of 4-mm solid component size for treatment of subsolid nodules. This strategy yielded an ICER of $52 993 per QALY (95% CI: 44 407, 64 372). Probabilistic sensitivity analysis showed this was the optimal strategy under a range of parameter variations. Conclusion Treatment of pure ground-glass nodules was not cost-effective. Strategies that use modifications of the Lung CT Screening Reporting and Data System guidelines were cost-effective for treating part-solid nodules; an optimal threshold of 4 mm for the solid component yielded the most quality-adjusted life years. © RSNA, 2021 Online supplemental material is available for this article.

Cost-Effectiveness of Follow-Up for Subsolid Pulmonary Nodules in High-Risk Patients.

OBJECTIVE: To evaluate the cost-effectiveness of a number of follow-up guidelines and variants for subsolid pulmonary nodules. METHODS: We used a simulation model informed by data from the literature and the National Lung Screening Trial to simulate patients with ground-glass nodules (GGNs) detected at baseline computed tomography undergoing follow-up. The nodules were allowed to grow and develop solid components over time. We tested the guidelines generated by varying follow-up recommendations for low-risk nodules, that is, pure GGNs or those stable over time. For each guideline, we computed average US costs and quality-adjusted life-years (QALYs) gained per patient and identified the incremental cost-effectiveness ratios of those on the efficient frontier. In addition, we compared the costs and effects of the most recently released version of the Lung Computed Tomography Screening Reporting and Data System (Lung-RADS), version 1.1, with those of the previous version, 1.0. Finally, we performed sensitivity analyses of our results by varying several relevant parameters. RESULTS: Relative to the no follow-up scenario, the follow-up guideline system that was cost-effective at a willingness-to-pay of $100,000/QALY and had the greatest QALY assigned low-risk nodules a 2-year follow-up interval and stopped follow-up after 2 years for GGNs and after 5 years for part-solid nodules; this strategy yielded an incremental cost-effectiveness ratio of $99,970. Lung-RADS version 1.1 was found to be less costly but no less effective than Lung-RADS version 1.0. These findings were essentially stable under a range of sensitivity analyses. CONCLUSIONS: Ceasing follow-up for low-risk subsolid nodules after 2 to 5 years of stability is more cost-effective than perpetual follow-up. Lung-RADS version 1.1 was cheaper but similarly effective to version 1.0.

Cost-effectiveness of pembrolizumab for advanced non-small cell lung cancer patients with varying comorbidity burden.

OBJECTIVES: While previous cost-effectiveness studies on pembrolizumab in stage IV non-small cell lung cancer (NSCLC) have found these regimens to be cost-effective, their reliance on randomized controlled trial (RCT) data with strict inclusion criteria limits generalizability to patients with comorbidities. We estimated the cost-effectiveness of first-line pembrolizumab for patients with various comorbidities. MATERIALS AND METHODS: In our base case analysis, we studied pembrolizumab plus chemotherapy (pembrolizumab combination therapy) versus chemotherapy alone. In a secondary analysis, we considered only patients with PD-L1 expression of at least 50% (PD-L1-high) and evaluated pembrolizumab monotherapy, pembrolizumab combination therapy, and chemotherapy alone. Microsimulation models were developed for the base case and the PD-L1-high analyses. To estimate outcomes of patients with differing comorbidities, we combined survival data from patients with few or no comorbidities from the RCTs with estimates from the general population obtained from the Surveillance, Epidemiology, and End Results (SEER)-Medicare database. Comorbidity burden level was divided into three groups based on the Charlson score (equal to 0, 1, or 2+); patients with various other specific comorbidities were also analyzed. Incremental cost-effectiveness ratios (ICER) were compared to a willingness-to-pay (WTP) threshold of $100,000/quality-adjusted life-year (QALY). RESULTS: In the Charlson 0, Charlson 1, and Charlson 2+ patient populations, estimated ICERs for pembrolizumab combination therapy in the base case model were $173,919/QALY, $175,165/QALY, and $181,777/QALY, respectively, compared to chemotherapy. In the PD-L1-high model, the Charlson 0, Charlson 1, and Charlson 2+ patients had ICERs of $147,406/QALY, $149,026/QALY, and $154,521/QALY with pembrolizumab combination therapy versus chemotherapy. Pembrolizumab monotherapy was weakly dominated for each comorbidity group in the PD-L1-high model. CONCLUSION: For patients with stage IV NSCLC and varying comorbidity burden, first-line treatment with pembrolizumab does not represent a cost-effective strategy compared to chemotherapy. Resources should be focused on collecting immunotherapy survival data for more representative NSCLC patient populations.

Cost and Utilization of Lung Cancer End-of-Life Care Among Racial-Ethnic Minority Groups in the United States.

BACKGROUND: The end-of-life period is a crucial time in lung cancer care. To have a better understanding of the racial-ethnic disparities in health care expenditures, access, and quality, we evaluated these disparities specifically in the end-of-life period for patients with lung cancer in the U.S. MATERIALS AND METHODS: We used the Surveillance, Epidemiology, and End Results (SEER)-Medicare database to analyze characteristics of lung cancer care among those diagnosed between the years 2000 and 2011. Linear and logistic regression models were constructed to measure racial-ethnic disparities in end-of-life care cost and utilization among non-Hispanic (NH) Asian, NH black, Hispanic, and NH white patients while controlling for other risk factors such as age, sex, and SEER geographic region. RESULTS: Total costs and hospital utilization were, on average, greater among racial-ethnic minorities compared with NH white patients in the last month of life. Among patients with NSCLC, the relative total costs were 1.27 (95% confidence interval [CI], 1.21-1.33) for NH black patients, 1.36 (95% CI, 1.25-1.49) for NH Asian patients, and 1.21 (95% CI, 1.07-1.38) for Hispanic patients. Additionally, the odds of being admitted to a hospital for NH black, NH Asian, and Hispanic patients were 1.22 (95% CI, 1.15-1.30), 1.47 (95% CI, 1.32-1.63), and 1.18 (95% CI, 1.01-1.38) times that of NH white patients, respectively. Similar results were found for patients with SCLC. CONCLUSION: Minority patients with lung cancer have significantly higher end-of-life medical expenditures than NH white patients, which may be explained by a greater intensity of care in the end-of-life period. IMPLICATIONS FOR PRACTICE: This study investigated racial-ethnic disparities in the cost and utilization of medical care among lung cancer patients during the end-of-life period. Compared with non-Hispanic white patients, racial-ethnic minority patients were more likely to receive intensive care in their final month of life and had statistically significantly higher end-of-life care costs. The findings of this study may lead to a better understanding of the racial-ethnic disparities in end-of-life care, which can better inform future end-of-life interventions and help health care providers develop less intensive and more equitable care, such as culturally competent advanced care planning programs, for all patients.

Cancer Risk in Subsolid Nodules in the National Lung Screening Trial.

Background Subsolid pulmonary nodules, comprising pure ground-glass nodules (GGNs) and part-solid nodules (PSNs), have a high risk of indolent malignancy. Lung Imaging Reporting and Data System (Lung-RADS) nodule management guidelines are based on expert opinion and lack independent validation. Purpose To evaluate Lung-RADS estimates of the malignancy rates of subsolid nodules, using nodules from the National Lung Screening Trial (NLST), and to compare Lung-RADS to the NELSON trial classification as well as the Brock University calculator. Materials and Methods Subsets of GGNs and PSNs were selected from the NLST for this retrospective study. A thoracic radiologist reviewed the baseline and follow-up CT images, confirmed that they were true subsolid nodules, and measured the nodules. The primary outcome for each nodule was the development of malignancy within the follow-up period (median, 6.5 years). Nodules were stratified according to Lung-RADS, NELSON trial criteria, and the Brock model. For analyses, nodule subsets were weighted on the basis of frequency in the NLST data set. Nodule stratification models were tested by using receiver operating characteristic curves. Results A total of 622 nodules were evaluated, of which 434 nodules were subsolid. At baseline, 304 nodules were classified as Lung-RADS category 2, with a malignancy rate of 3%, which is greater than the 1% in Lung-RADS (P = .004). The malignancy rate for GGNs smaller than 10 mm (two of 129, 1.3%) was smaller than that for GGNs measuring 10-19 mm (11 of 153, 6%) (P = .01). The malignancy rate for Lung-RADS category 3 was 14% (13 of 67), which is greater than the reported 2% in Lung-RADS (P < .001). The Brock model predicted malignancy better than Lung-RADS and the NELSON trial scheme (area under the receiver operating characteristic curve = 0.78, 0.70, and 0.67, respectively; P = .02 for Brock model vs NELSON trial scheme). Conclusion Subsolid nodules classified as Lung Imaging Reporting and Data System (Lung-RADS) categories 2 and 3 have a higher risk of malignancy than reported. The Brock risk calculator performed better than measurement-based classification schemes such as Lung-RADS. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Kauczor and von Stackelberg in this issue.

A simulation study of the effect of lung cancer screening in China, Japan, Singapore, and South Korea.

More than 50% of the world's lung cancer cases occur in Asia and more than 20% of cancer deaths in Asia are attributable to lung cancer. The U.S. National Lung Screening Trial has shown that lung cancer screening with computed tomography (CT) can reduce lung cancer deaths. Using the Lung Cancer Policy Model-Asia (LCPM-Asia), we estimated the potential mortality reduction achievable through the implementation of CT-based lung cancer screening in China, Japan, Singapore, and South Korea. The LCPM-Asia was calibrated to the smoking prevalence of each of the aforementioned countries based on published national surveys and to lung cancer mortality rates from the World Health Organization. The calibrated LCPM-Asia was then used to simulate lung cancer deaths under screening and no-screening scenarios for the four countries. Using screening eligibility criteria recommended by the U.S. Centers for Medicare & Medicaid Services (CMS), which are based on age and smoking history, we estimated the lung cancer mortality reduction from screening through year 2040. By 2040, lung cancer screening would result in 91,362 life-years gained and 4.74% mortality reduction in South Korea; 290,325 life-years gained and 4.33% mortality reduction in Japan; 3,014,215 life-years gained and 4.22% mortality reduction in China; and 8,118 life-years gained and 3.76% mortality reduction in Singapore. As for mortality reduction by smoker type, current smokers would have the greatest mortality reduction in each country, ranging from 5.56% in Japan to 6.86% in Singapore. Among the four countries, lung cancer screening under CMS eligibility criteria was most effective in South Korea and least effective in Singapore. Singapore's low smoking prevalence and South Korea's aging population and higher smoking prevalence may partially explain the discrepancy in effectiveness. CT screening was shown to be promising as a means of reducing lung cancer mortality in the four countries.

Disparities and Trends in Genetic Testing and Erlotinib Treatment among Metastatic Non-Small Cell Lung Cancer Patients.

BACKGROUND: Despite reports of socioeconomic disparities in rates of genetic testing and targeted therapy treatment for metastatic non-small cell lung cancer (NSCLC), little is known about whether such disparities are changing over time. METHODS: We performed a retrospective analysis to identify disparities and trends in genetic testing and treatment with erlotinib. Using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database, we identified 9,900 patients with stage IV NSCLC diagnosed in 2007 to 2011 at age 65 or older. We performed logistic regression analyses to identify patient factors associated with odds of receiving a genetic test and erlotinib treatment, and to assess trends in these differences with respect to diagnosis year. RESULTS: Patients were more likely to receive genetic testing if they were under age 75 at diagnosis [odds ratio (OR), 1.55] independent of comorbidity level, and this age-based gap showed a decrease over time (OR, 0.93). For untested patients, erlotinib treatment was associated with race (OR, 0.58, black vs. white; OR, 2.45, Asian vs. white), and was more likely among female patients (OR, 1.45); for tested patients, erlotinib treatment was less likely among low-income patients (OR, 0.32). Most of these associations persisted or increased in magnitude. CONCLUSIONS: Race and sex are associated with rates of erlotinib treatment for patients who did not receive genetic testing, and low-income status is associated with treatment rates for those who did receive testing. The racial disparity remained stable over time, while the income-based disparity grew larger. IMPACT: Attention to reducing disparities is needed as precision cancer treatments continue to be developed.

A Decision Analysis of Follow-up and Treatment Algorithms for Nonsolid Pulmonary Nodules.

Purpose To evaluate management strategies and treatment options for patients with ground-glass nodules (GGNs) by using decision-analysis models. Materials and Methods A simulation was developed for 1 000 000 hypothetical patients with GGNs undergoing follow-up per the Lung Imaging Reporting and Data System (Lung-RADS) recommendations. The initial age range was 55-75 years (mean, 64 years). Nodules could grow and develop solid components over time. Clinically significant malignancy rates were calibrated to data from the National Lung Screening Trial. Annual versus 3-year-interval follow-up of Lung-RADS category 2 nodules was compared, and different treatment strategies were tested (stereotactic body radiation therapy, surgery, and no therapy). Results Overall, 2.3% (22 584 of 1 000 000) of nodules were clinically significant malignancies; 6.3% (62 559 of 1 000 000) of nodules were treated. Only 30% (18 668 of 62 559) of Lung-RADS category 4B or 4X nodules were clinically significant malignancies. The risk of clinically significant malignancy for persistent nonsolid nodules after baseline was higher than Lung-RADS estimates for categories 2 and 3 (3% vs <1% and 1%-2%, respectively). Overall survival (OS) at 10 years was 72% (527 827 of 737 306; 95% confidence interval [CI]: 71%, 72%) with annual follow-up and 71% (526 507 of 737 306; 95% CI: 71%, 72%) with 3-year-interval follow-up (P < .01). At 10 years, OS among patients whose nodules progressed to Lung-RADS category 4B or 4X was 80% after radiation therapy (49 945 of 62 559; 95% CI: 80%, 80%), 79% after surgery (49 139 of 62 559; 95% CI: 78%, 79%), and 74% after no therapy (46 512 of 62 559; 95% CI: 74%, 75%) (P < .01). Conclusion Simulation modeling suggests that the follow-up interval for evaluating ground-glass nodules can be increased from 1 year to 3 years with minimal change in outcomes. Stereotactic body radiation therapy demonstrated the best outcomes compared with lobectomy and with no therapy for nonsolid nodules. © RSNA, 2018 Online supplemental material is available for this article.

Lung cancer costs by treatment strategy and phase of care among patients enrolled in Medicare.

BACKGROUND: We studied trends in lung cancer treatment cost over time by phase of care, treatment strategy, age, stage at diagnosis, and histology. METHODS: Using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database for years 1998-2013, we allocated total and patient-liability costs into the following phases of care for 145 988 lung cancer patients: prediagnosis, staging, surgery, initial, continuing, and terminal. Patients served as self-controls to determine cancer-attributable costs based on individual precancer diagnosis healthcare costs. We fit linear regression models to determine cost by age and calendar year for each stage at diagnosis, histology, and treatment strategy and presented all costs in 2017 US dollars. RESULTS: Monthly healthcare costs prior to lung cancer diagnosis were $861 for a 70 years old in 2017 and rose by an average of $17 per year (P < 0.001). Surgery in 2017 cost $30 096, decreasing by $257 per year (P = 0.007). Chemotherapy and radiation costs remained stable or increased for most stage and histology groups, ranging from $4242 to $8287 per month during the initial six months of care. Costs during the final six months of life decreased for those who died of lung cancer or other causes. CONCLUSIONS: Cost-effectiveness analyses of lung cancer control interventions in the United States have been using outdated and incomplete treatment cost estimates. Our cost estimates enable updated cost-effectiveness analyses to determine the benefit of lung cancer control from a health economics point of view.

Population impact of lung cancer screening in the United States: Projections from a microsimulation model.

BACKGROUND: Previous simulation studies estimating the impacts of lung cancer screening have ignored the changes in smoking prevalence over time in the United States. Our primary rationale was to perform, to our knowledge, the first simulation study that estimates the health outcomes of lung cancer screening with explicit modeling of smoking trends for the whole US population. METHODS/FINDINGS: Utilizing a well-validated microsimulation model, we estimated the benefits and harms of an annual low-dose computed tomography screening scenario with a realistic screening adherence rate versus a no-screening scenario for the US population from 2016-2030. The Centers for Medicare and Medicaid Services (CMS) eligibility criteria were applied: age 55-77 years at time of screening, history of at least 30 pack-years of smoking, and current smoker or former smoker with fewer than 15 years since quitting. In the screened population, cumulative mortality reduction was projected to reach 16.98% (95% CI 16.90%-17.07%). Cumulative mortality reduction was estimated to be 3.52% (95% CI 3.50%-3.53%) for the overall study population, with annual mortality reduction peaking at 4.38% (95% CI 4.36%-4.41%) in 2021 and falling to 3.53% (95% CI 3.50%-3.56%) by 2030. Lung cancer screening would save a projected 148,484 life-years (95% CI 147,429-149,540) across the total population through 2030. There were estimated to be 9,054 (95% CI 9,011-9,098) overdiagnosed cases among the 252,429 (95% CI 251,208-253,649) screen-detected lung cancer diagnoses, yielding an overdiagnosis rate of 3.59%. The limitations of our study are that we do not explicitly model race or socioeconomic status and our model was calibrated to data from studies performed in academic centers, both of which may impact the generalizability of our results. We also exclusively model the effects of the CMS guidelines for lung cancer screening and not any other screening strategies. CONCLUSIONS: The mortality reduction and life-years gained estimated by this study are lower than those of single birth cohort studies. Single cohort studies neglect the changing dynamics of smoking behavior across generations, whereas this study reflects the trend of decreasing smoking prevalence since the 1960s. Maximum benefit could be derived from lung cancer screening through 2021; in later years, mortality reduction due to screening will decline. If a comprehensive screening program is not implemented in the near future, the opportunity to achieve these benefits will have passed.