Evaluation of the Benefits and Harms of Lung Cancer Screening With Low-Dose Computed Tomography: Modeling Study for the US Preventive Services Task Force.

Importance: The US Preventive Services Task Force (USPSTF) is updating its 2013 lung cancer screening guidelines, which recommend annual screening for adults aged 55 through 80 years who have a smoking history of at least 30 pack-years and currently smoke or have quit within the past 15 years. Objective: To inform the USPSTF guidelines by estimating the benefits and harms associated with various low-dose computed tomography (LDCT) screening strategies. Design, Setting, and Participants: Comparative simulation modeling with 4 lung cancer natural history models for individuals from the 1950 and 1960 US birth cohorts who were followed up from aged 45 through 90 years. Exposures: Screening with varying starting ages, stopping ages, and screening frequency. Eligibility criteria based on age, cumulative pack-years, and years since quitting smoking (risk factor-based) or on age and individual lung cancer risk estimation using risk prediction models with varying eligibility thresholds (risk model-based). A total of 1092 LDCT screening strategies were modeled. Full uptake and adherence were assumed for all scenarios. Main Outcomes and Measures: Estimated lung cancer deaths averted and life-years gained (benefits) compared with no screening. Estimated lifetime number of LDCT screenings, false-positive results, biopsies, overdiagnosed cases, and radiation-related lung cancer deaths (harms). Results: Efficient screening programs estimated to yield the most benefits for a given number of screenings were identified. Most of the efficient risk factor-based strategies started screening at aged 50 or 55 years and stopped at aged 80 years. The 2013 USPSTF-recommended criteria were not among the efficient strategies for the 1960 US birth cohort. Annual strategies with a minimum criterion of 20 pack-years of smoking were efficient and, compared with the 2013 USPSTF-recommended criteria, were estimated to increase screening eligibility (20.6%-23.6% vs 14.1% of the population ever eligible), lung cancer deaths averted (469-558 per 100 000 vs 381 per 100 000), and life-years gained (6018-7596 per 100 000 vs 4882 per 100 000). However, these strategies were estimated to result in more false-positive test results (1.9-2.5 per person screened vs 1.9 per person screened with the USPSTF strategy), overdiagnosed lung cancer cases (83-94 per 100 000 vs 69 per 100 000), and radiation-related lung cancer deaths (29.0-42.5 per 100 000 vs 20.6 per 100 000). Risk model-based vs risk factor-based strategies were estimated to be associated with more benefits and fewer radiation-related deaths but more overdiagnosed cases. Conclusions and Relevance: Microsimulation modeling studies suggested that LDCT screening for lung cancer compared with no screening may increase lung cancer deaths averted and life-years gained when optimally targeted and implemented. Screening individuals at aged 50 or 55 years through aged 80 years with 20 pack-years or more of smoking exposure was estimated to result in more benefits than the 2013 USPSTF-recommended criteria and less disparity in screening eligibility by sex and race/ethnicity.

Cost-Effectiveness Analysis of Lung Cancer Screening in the United States: A Comparative Modeling Study.

Background: Recommendations vary regarding the maximum age at which to stop lung cancer screening: 80 years according to the U.S. Preventive Services Task Force (USPSTF), 77 years according to the Centers for Medicare & Medicaid Services (CMS), and 74 years according to the National Lung Screening Trial (NLST). Objective: To compare the cost-effectiveness of different stopping ages for lung cancer screening. Design: By using shared inputs for smoking behavior, costs, and quality of life, 4 independently developed microsimulation models evaluated the health and cost outcomes of annual lung cancer screening with low-dose computed tomography (LDCT). Data Sources: The NLST; Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial; SEER (Surveillance, Epidemiology, and End Results) program; Nurses' Health Study and Health Professionals Follow-up Study; and U.S. Smoking History Generator. Target Population: Current, former, and never-smokers aged 45 years from the 1960 U.S. birth cohort. Time Horizon: 45 years. Perspective: Health care sector. Intervention: Annual LDCT according to NLST, CMS, and USPSTF criteria. Outcome Measures: Incremental cost-effectiveness ratios (ICERs) with a willingness-to-pay threshold of $100 000 per quality-adjusted life-year (QALY). Results of Base-Case Analysis: The 4 models showed that the NLST, CMS, and USPSTF screening strategies were cost-effective, with ICERs averaging $49 200, $68 600, and $96 700 per QALY, respectively. Increasing the age at which to stop screening resulted in a greater reduction in mortality but also led to higher costs and overdiagnosis rates. Results of Sensitivity Analysis: Probabilistic sensitivity analysis showed that the NLST and CMS strategies had higher probabilities of being cost-effective (98% and 77%, respectively) than the USPSTF strategy (52%). Limitation: Scenarios assumed 100% screening adherence, and models extrapolated beyond clinical trial data. Conclusion: All 3 sets of lung cancer screening criteria represent cost-effective programs. Despite underlying uncertainty, the NLST and CMS screening strategies have high probabilities of being cost-effective. Primary Funding Source: CISNET (Cancer Intervention and Surveillance Modeling Network) Lung Group, National Cancer Institute.

Treatment capacity required for full-scale implementation of lung cancer screening in the United States.

BACKGROUND: Full-scale implementation of lung cancer screening in the United States will increase detection of early stages. This study was aimed at assessing the capacity required for treating those cancers. METHODS: A well-established microsimulation model was extended with treatment data from the National Cancer Database. We assessed how treatment demand would change when implementing lung cancer screening in 2018. Three policies were assessed: 1) annual screening of current smokers and former smokers who quit fewer than 15 years ago, aged 55 to 80 years, with a smoking history of at least 30 pack-years (US Preventive Services Task Force [USPSTF] recommendations); 2) annual screening of current smokers and former smokers who quit fewer than 15 years ago, aged 55 to 77 years, with a smoking history of at least 30 pack-years (Centers for Medicare and Medicaid Services [CMS] recommendations); and 3) annual screening of current smokers and former smokers who quit fewer than 10 years ago, aged 55 to 75 years, with a smoking history of at least 40 pack-years (the most cost-effective policy in Ontario [Ontario]). The base-case screening adherence was a constant 50%. Sensitivity analyses assessed other adherence levels, including a linear buildup to 50% between 2018 and 2027. RESULTS: The USPSTF policy would require 37.0% more lung cancer surgeries in 2015-2040 than no screening, 2.2% less radiotherapy, and 5.4% less chemotherapy; 5.7% more patients would require any therapy. The increase in surgical demand would be 96.1% in 2018, 46.0% in 2023, 38.3% in 2028, and 24.9% in 2040. Adherence strongly influenced results. By 2018, surgical demand would range from 52,619 (20% adherence) to 96,121 (80%). With a gradual buildup of adherence, the increase in surgical demand would be 9.6% in 2018, 38.3% in 2023, 42.0% in 2028, and 24.4% in 2040. Results for the CMS and Ontario policies were similar, although the changes in comparison with no screening were smaller. CONCLUSIONS: Full-scale implementation of lung cancer screening causes a major increase in surgical demand, with a peak within the first 5 years. A gradual buildup of adherence can spread this peak over time. Careful surgical capacity planning is essential for successfully implementing screening.

Systematic Review and Meta-Analysis of Community- and Choice-Based Health State Utility Values for Lung Cancer.

BACKGROUND: Using appropriate health state utility values (HSUVs) is critical for economic evaluation of new lung cancer interventions, such as low-dose computed tomography screening and immunotherapy. Therefore, we provide a systematic review and meta-analysis of community- and choice-based HSUVs for lung cancer. METHODS: On 6 March 2017, we conducted a systematic search of the following databases: Embase, Ovid MEDLINE, Web of Science, Cochrane CENTRAL, Google Scholar, and the School of Health and Related Research Health Utility Database. The search was updated on 17 April 2019. Studies reporting mean or median lung cancer-specific HSUVs including a measure of variance were included and assessed for relevance and validity. Studies with high relevance (i.e. community- and choice-based) were further analysed. Mean HSUVs were pooled using random-effects models for all stages, stages I-II, and stages III-IV. For studies with a control group, we calculated the disutility due to lung cancer. A sensitivity analysis included only the methodologically most comparable studies (i.e. using the EQ-5D instrument and matching tariff). Subgroup analyses were conducted by time to death, histology, sex, age, treatment modality, treatment line, and progression status. RESULTS: We identified and analysed 27 studies of high relevance. The pooled HSUV was 0.68 (95% confidence interval [CI] 0.61-0.75) for all stages, 0.78 (95% CI 0.70-0.86) for stages I-II, and 0.69 (95% CI 0.65-0.73) for stages III-IV (p = 0.02 vs. stage I-II). Heterogeneity was present in each pooled analysis (p < 0.01; I2 = 92-99%). Disutility due to lung cancer ranged from 0.11 (95% CI 0.05-0.17) to 0.27 (95% CI 0.18-0.36). In the sensitivity analysis with the methodologically most comparable studies, stage-specific HSUVs varied by country. Such studies were only identified for Canada, China, Spain, the UK, the USA, Denmark, Germany, and Thailand. In the subgroup analysis by time to death, HSUVs for metastatic non-small-cell lung cancer ranged from 0.83 (95% CI 0.82-0.85) at ≥ 360 days from death to 0.56 (95% CI 0.46-0.66) at < 30 days from death. Among patients with metastatic non-small-cell lung cancer, HSUVs were lower for those receiving third- or fourth-line treatment and for those with progressed disease. Results of subgroup analyses by histology, sex, age, and treatment modality were ambiguous. CONCLUSIONS: The presented evidence supports the use of stage- and country-specific HSUVs. However, such HSUVs are unavailable for most countries. Therefore, our pooled HSUVs may provide the best available stage-specific HSUVs for most countries. For metastatic non-small-cell lung cancer, adjusting for the decreased HSUVs in the last year of life may be considered, as may further stratification of HSUVs by treatment line or progression status. If required, HSUVs for other health states may be identified using our comprehensive breakdown of study characteristics.

Trends in lung cancer risk and screening eligibility affect overdiagnosis estimates.

OBJECTIVES: The degree of overdiagnosis due to lung cancer screening in the general US population remains unknown. Estimates may be influenced by the method used and by decreasing smoking trends, which reduce lung cancer risk and screening eligibility over time. Therefore, we aimed to estimate the degree of overdiagnosis due to lung cancer screening in the general US population, using three distinct methods. MATERIAL AND METHODS: The MISCAN-Lung model was used to project lung cancer incidence and overdiagnosis in the general US population between 2018-2040, assuming perfect adherence to the United States Preventive Task Force recommendations. MISCAN-Lung was calibrated to the NLST and PLCO trials and incorporates birth-cohort-specific smoking trends and life expectancies. We estimated overdiagnosis using the cumulative excess-incidence approach, the annual excess-incidence approach, and the microsimulation approach. RESULTS: Using the cumulative excess-incidence approach, 10.5 % of screen-detected cases were overdiagnosed in the 1950 birth-cohort compared to 5.9 % in the 1990 birth-cohort. Incidence peaks and drops due to screening were larger for older birth-cohorts than younger birth-cohorts. In the general US population, these differing incidence peaks and drops across birth-cohorts overlap. Therefore, annual excess-incidence would be absent between 2029-2040, suggesting no overdiagnosis occurs. Using the microsimulation approach, overdiagnosis among screen-detected cases increased from 7.1 % to 9.5 % between 2018-2040, while overdiagnosis among all lung cancer cases decreased from 3.7 % to 1.4 %. CONCLUSION: Overdiagnosis studies should use appropriate methods to account for trends in background risk and screening eligibility in the general population. Estimates from randomized trials, based on the cumulative excess-incidence approach, are not generalizable to the general population. The annual excess-incidence approach does not account for trends in background risk and screening eligibility, and falsely suggests no overdiagnosis occurs in the general population. Using the microsimulation approach, overdiagnosis was limited but not nil. Overdiagnosis increased among screen-detected cases, while overdiagnosis among all cases decreased.

Uptake of minimally invasive surgery and stereotactic body radiation therapy for early stage non-small cell lung cancer in the USA: an ecological study of secular trends using the National Cancer Database.

BACKGROUND: We aimed to assess the uptake of minimally invasive surgery (MIS) and stereotactic body radiation therapy (SBRT) among early stage (stage IA-IIB) non-small cell lung cancer (NSCLC) cases in the USA, and the rate of conversions from MIS to open surgery. MATERIALS AND METHODS: Data were obtained from the US National Cancer Database, a nationwide facility-based cancer registry capturing up to 70% of incident cancer cases in the USA. We included cases diagnosed with early stage (clinical stages IA-IIB) NSCLC between 2010 and 2014. In an ecological analysis, we assessed changes in treatment by year of diagnosis. Among surgically treated cases, we assessed the uptake of MIS and whether conversion to open surgery took place. For cases that received thoracic radiotherapy, we assessed the uptake of SBRT. RESULTS: Among 117 370 selected cases, radiotherapy use increased 3.4 percentage points between 2010 and 2014 (p<0.0001). Surgical treatments decreased 3.5 percentage points (p<0.0001). Rates of non-treatment remained stable (range: 10.0%-10.6% (p=0.4066)). Among surgically treated stage IA cases, uptake of MIS increased from 28.7% (95% CI 27.8% to 29.7%) in 2010 to 48.6% (95% CI 47.6% to 49.6%) in 2014 (p<0.0001), while conversions decreased from 17.0% (95% CI 15.6% to 18.6%) in 2010 to 9.1% (95% CI 8.3% to 10.0%) in 2014 (p<0.0001). MIS uptake among stages IB-IIB was lower and conversion rates were higher, but time trends were similar. Uptake of SBRT among stage IA receiving thoracic radiotherapy increased from 53.4% (95% CI 51.2% to 55.6%) in 2010 to 73.0% (95% CI 71.4% to 74.6%) in 2014 (p<0.0001). SBRT uptake among stage IB increased from 32.5% (95% CI 29.9% to 35.2%) in 2010 to 48.2% (95% CI 45.6% to 50.8%) in 2014 (p<0.0001). CONCLUSION: Between 2010 and 2014, uptake of MIS and SBRT among early stage NSCLC significantly increased, while the rate of conversions to open surgery significantly decreased. Continuing these trends may contribute to improving patient care, in particular with the expected increase in early stages due to the implementation of lung cancer screening.

Disparities in Receiving Guideline-Concordant Treatment for Lung Cancer in the United States.

Rationale: The level of adherence to lung cancer treatment guidelines in the United States is unclear. In addition, it is unclear whether previously identified disparities by racial or ethnic group and by age persist across all clinical subgroups.Objectives: To assess the level of adherence to the minimal lung cancer treatment recommended by the National Comprehensive Cancer Network guidelines (guideline-concordant treatment) in the United States, and to assess the persistence of disparities by racial or ethnic group and by age across all clinical subgroups.Methods: We evaluated whether 441,812 lung cancer cases in the National Cancer Database diagnosed between 2010 and 2014 received guideline-concordant treatment. Logistic regression models were used to assess possible disparities in receiving guideline-concordant treatment by racial or ethnic group and by age across all clinical subgroups, and whether these persist after adjusting for patient, tumor, and health care provider characteristics.Results: Overall, 62.1% of subjects received guideline-concordant treatment (range across clinical subgroups = 50.4-76.3%). However, 21.6% received no treatment (range = 10.3-31.4%) and 16.3% received less intensive treatment than recommended (range = 6.4-21.6%). Among the most common less intensive treatments for all subgroups was "conventionally fractionated radiotherapy only" (range = 2.5-16.0%), as was "chemotherapy only" for nonmetastatic subgroups (range = 1.2-13.7%), and "conventionally fractionated radiotherapy and chemotherapy" for localized non-small-cell lung cancer (5.9%). Guideline-concordant treatment was less likely with increasing age, despite adjusting for relevant covariates (age ≥ 80 yr compared with <50 yr: adjusted odds ratio = 0.12, 95% confidence interval = 0.12-0.13). This disparity was present in all clinical subgroups. In addition, non-Hispanic black patients were less likely to receive guideline-concordant treatment than non-Hispanic white patients (adjusted odds ratio = 0.78, 95% confidence interval = 0.76-0.80). This disparity was present in all clinical subgroups, although statistically nonsignificant for extensive disease small-cell lung cancer.Conclusions: Between 2010 and 2014, many patients with lung cancer in the United States received no treatment or less intensive treatment than recommended. Particularly, elderly patients with lung cancer and non-Hispanic black patients are less likely to receive guideline-concordant treatment. Patterns of care among those receiving less intensive treatment than recommended suggest room for improved uptake of treatments such as stereotactic body radiation therapy for subjects with localized non-small-cell lung cancer.

A Comparative Modeling Analysis of Risk-Based Lung Cancer Screening Strategies.

BACKGROUND: Risk-prediction models have been proposed to select individuals for lung cancer screening. However, their long-term effects are uncertain. This study evaluates long-term benefits and harms of risk-based screening compared with current United States Preventive Services Task Force (USPSTF) recommendations. METHODS: Four independent natural history models were used to perform a comparative modeling study evaluating long-term benefits and harms of selecting individuals for lung cancer screening through risk-prediction models. In total, 363 risk-based screening strategies varying by screening starting and stopping age, risk-prediction model used for eligibility (Bach, PLCOm2012, or Lung Cancer Death Risk Assessment Tool [LCDRAT]), and risk threshold were evaluated for a 1950 US birth cohort. Among the evaluated outcomes were percentage of individuals ever screened, screens required, lung cancer deaths averted, life-years gained, and overdiagnosis. RESULTS: Risk-based screening strategies requiring similar screens among individuals ages 55-80 years as the USPSTF criteria (corresponding risk thresholds: Bach = 2.8%; PLCOm2012 = 1.7%; LCDRAT = 1.7%) averted considerably more lung cancer deaths (Bach = 693; PLCOm2012 = 698; LCDRAT = 696; USPSTF = 613). However, life-years gained were only modestly higher (Bach = 8660; PLCOm2012 = 8862; LCDRAT = 8631; USPSTF = 8590), and risk-based strategies had more overdiagnosed cases (Bach = 149; PLCOm2012 = 147; LCDRAT = 150; USPSTF = 115). Sensitivity analyses suggest excluding individuals with limited life expectancies (<5 years) from screening retains the life-years gained by risk-based screening, while reducing overdiagnosis by more than 65.3%. CONCLUSIONS: Risk-based lung cancer screening strategies prevent considerably more lung cancer deaths than current recommendations do. However, they yield modest additional life-years and increased overdiagnosis because of predominantly selecting older individuals. Efficient implementation of risk-based lung cancer screening requires careful consideration of life expectancy for determining optimal individual stopping ages.

Influence of Ossicular Chain Damage on Hearing After Chronic Otitis Media and Cholesteatoma Surgery: A Systematic Review and Meta-analysis.

IMPORTANCE: Physicians should ideally be able to provide patients with chronic otitis media and/or cholesteatoma specific information about postoperative hearing outcome, based on their level of preoperative ossicular chain damage (OCD). OBJECTIVE: To identify the influence of preoperative OCD on hearing outcomes in patients after chronic otitis media and/or cholesteatoma surgery. DATA SOURCES: PubMed, EMBASE, and the Cochrane Library databases were systematically searched for available evidence, without any constraints, on December 13, 2014, for articles published between January 1, 1975, and December 13, 2014. STUDY SELECTION: We reviewed the literature for articles assessing the prognostic value of OCD on postoperative hearing outcome (air-bone gap [ABG] in decibels), using Austin-Kartush criteria or independent OCD classification systems. We assessed relevance and validity using a self-designed critical appraisal tool based on the Cochrane Collaboration's risk of bias tool. DATA EXTRACTION: Characteristics of study populations and postoperative ABGs in decibels were extracted from all included studies by 4 authors (E.F.B., M.N.G., N.J.K., A.S.H.J.L.). RESULTS: The tested hypothesis was formulated before data collection. Primary study outcome was defined as postoperative adult hearing outcomes after COM and/or cholesteatoma surgery defined as mean postoperative ABG. Our search yielded 5661 articles. Nine articles with high relevance were included. Pooled results of studies using the Austin-Kartush criteria showed a significant (P < .001) difference in mean ABG in favor of group B, when comparing group B (patients with malleus present, stapes absent; 11.1 [95% CI, 10.3-11.8] dB) to group C (patients with malleus absent, stapes present; 15.7 [95% CI, 14.6-16.7] dB) and group B to group D (patients with malleus absent, stapes absent; 16.5 [95% CI, 15.2-17.9] dB). Three studies using independent OCD classification criteria found no influence of stapes structure (intact stapes suprastructure, 13.5 [95% CI, 10.3-16.7], 15.1 [95% CI, 11.8-18.3], and 21.9 [95% CI, 15.0-28.8] dB vs absent stapes structure, 12.8 [95% CI, 9.5-16.1], 19.5 [95% CI, 14.9-24.1], and 30.2 [95% CI, 24.7-35.8] dB) on postoperative ABG. One study reported a significant (P = .04) difference in mean ABG between patients with present (18.9 [95% CI, 15.7-22.1] dB) and absent (24.4 [95% CI, 20.2-28.6] dB) malleus. CONCLUSIONS AND RELEVANCE: Pooled results of Austin-Kartush studies showed that in patients with COM, with or without cholesteatoma, the malleus status is a significant predictor of postoperative hearing outcome, independent of the stapes condition. Studies reporting on individual ossicle status supported this finding by showing that only malleus condition influenced postoperative hearing outcome. These findings are based on level IV evidence, which indicates the need for future high-level evidence studies.