Showing papers by "Eric J. Feuer published in 2021"

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

Abstract: 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.

Colorectal Cancer Screening: An Updated Modeling Study for the US Preventive Services Task Force.

Abstract: Importance The US Preventive Services Task Force (USPSTF) is updating its 2016 colorectal cancer screening recommendations. Objective To provide updated model-based estimates of the benefits, burden, and harms of colorectal cancer screening strategies and to identify strategies that may provide an efficient balance of life-years gained (LYG) from screening and colonoscopy burden to inform the USPSTF. Design, setting, and participants Comparative modeling study using 3 microsimulation models of colorectal cancer screening in a hypothetical cohort of 40-year-old US individuals at average risk of colorectal cancer. Exposures Screening from ages 45, 50, or 55 years to ages 70, 75, 80, or 85 years with fecal immunochemical testing (FIT), multitarget stool DNA testing, flexible sigmoidoscopy alone or with FIT, computed tomography colonography, or colonoscopy. All persons with an abnormal noncolonoscopy screening test result were assumed to undergo follow-up colonoscopy. Screening intervals varied by test. Full adherence with all procedures was assumed. Main outcome and measures Estimated LYG relative to no screening (benefit), lifetime number of colonoscopies (burden), number of complications from screening (harms), and balance of incremental burden and benefit (efficiency ratios). Efficient strategies were those estimated to require fewer additional colonoscopies per additional LYG relative to other strategies. Results Estimated LYG from screening strategies ranged from 171 to 381 per 1000 40-year-olds. Lifetime colonoscopy burden ranged from 624 to 6817 per 1000 individuals, and screening complications ranged from 5 to 22 per 1000 individuals. Among the 49 strategies that were efficient options with all 3 models, 41 specified screening beginning at age 45. No single age to end screening was predominant among the efficient strategies, although the additional LYG from continuing screening after age 75 were generally small. With the exception of a 5-year interval for computed tomography colonography, no screening interval predominated among the efficient strategies for each modality. Among the strategies highlighted in the 2016 USPSTF recommendation, lowering the age to begin screening from 50 to 45 years was estimated to result in 22 to 27 additional LYG, 161 to 784 additional colonoscopies, and 0.1 to 2 additional complications per 1000 persons (ranges are across screening strategies, based on mean estimates across models). Assuming full adherence, screening outcomes and efficient strategies were similar by sex and race and across 3 scenarios for population risk of colorectal cancer. Conclusions and relevance This microsimulation modeling analysis suggests that screening for colorectal cancer with stool tests, endoscopic tests, or computed tomography colonography starting at age 45 years provides an efficient balance of colonoscopy burden and life-years gained.

Cost-effectiveness Evaluation of the 2021 US Preventive Services Task Force Recommendation for Lung Cancer Screening.

Abstract: Importance The US Preventive Services Task Force (USPSTF) issued its 2021 recommendation on lung cancer screening, which lowered the starting age for screening from 55 to 50 years and the minimum cumulative smoking exposure from 30 to 20 pack-years relative to its 2013 recommendation. Although costs are expected to increase because of the expanded screening eligibility criteria, it is unknown whether the new guidelines for lung cancer screening are cost-effective. Objective To evaluate the cost-effectiveness of the 2021 USPSTF recommendation for lung cancer screening compared with the 2013 recommendation and to explore the cost-effectiveness of 6 alternative screening strategies that maintained a minimum cumulative smoking exposure of 20 pack-years and an ending age for screening of 80 years but varied the starting ages for screening (50 or 55 years) and the number of years since smoking cessation (≤15, ≤20, or ≤25). Design, setting, and participants A comparative cost-effectiveness analysis using 4 independently developed microsimulation models that shared common inputs to assess the population-level health benefits and costs of the 2021 recommended screening strategy and 6 alternative screening strategies compared with the 2013 recommended screening strategy. The models simulated a 1960 US birth cohort. Simulated individuals entered the study at age 45 years and were followed up until death or age 90 years, corresponding to a study period from January 1, 2005, to December 31, 2050. Exposures Low-dose computed tomography in lung cancer screening programs with a minimum cumulative smoking exposure of 20 pack-years. Main outcomes and measures Incremental cost-effectiveness ratio (ICER) per quality-adjusted life-year (QALY) of the 2021 vs 2013 USPSTF lung cancer screening recommendations as well as 6 alternative screening strategies vs the 2013 USPSTF screening strategy. Strategies with a mean ICER lower than $100 000 per QALY were deemed cost-effective. Results The 2021 USPSTF recommendation was estimated to be cost-effective compared with the 2013 recommendation, with a mean ICER of $72 564 (range across 4 models, $59 493-$85 837) per QALY gained. The 2021 recommendation was not cost-effective compared with 6 alternative strategies that used the 20 pack-year criterion. Strategies associated with the most cost-effectiveness included those that expanded screening eligibility to include a greater number of former smokers who had not smoked for a longer duration (ie, ≤20 years and ≤25 years since smoking cessation vs ≤15 years since smoking cessation). In particular, the strategy that screened former smokers who quit within the past 25 years and began screening at age 55 years was associated with screening coverage closest to that of the 2021 USPSTF recommendation yet yielded greater cost-effectiveness, with a mean ICER of $66 533 (range across 4 models, $55 693-$80 539). Conclusions and relevance This economic evaluation found that the 2021 USPSTF recommendation for lung cancer screening was cost-effective; however, alternative screening strategies that maintained a minimum cumulative smoking exposure of 20 pack-years but included individuals who quit smoking within the past 25 years may be more cost-effective and warrant further evaluation.

Evaluation of the Benefits and Harms of Lung Cancer Screening With Low-Dose Computed Tomography: A Collaborative Modeling Study for the U.S. Preventive Services Task Force [Internet]

Abstract: Importance The U.S. Preventive Services Task Force (USPSTF) is updating its 2013 lung cancer screening recommendations. Objective To inform the USPSTF by evaluating the benefits and harms of low-dose computed tomography (LDCT) screening strategies by conducting simulation modeling; comparing strategies with varying starting and stopping ages, screening frequency, and eligibility criteria (based on smoking pack-years and years since quitting smoking or based on individual lung cancer risk); and identifying efficient strategies that provide the best balance of benefits (lung cancer deaths prevented and life-years gained [LYG]) and harms for a given level of LDCT screens. Design, Setting, and Participants Collaborative modeling with four lung cancer natural history models for individuals from the 1950 and 1960 birth cohorts from ages 45 to 90 years with no prior lung cancer diagnosis. Exposures Screening with LDCT with varying starting ages (45, 50, 55 years), stopping ages (75, 77, 80 years), and screening frequency (annual, biennial). Eligibility criteria based on either age, cumulative pack-years (20, 25, 30, 40 years) and years since quitting smoking (10, 15, 20, 25 years) (risk factor–based strategies) or age and individual lung cancer risk estimation using three established risk prediction models (Bach, Lung Cancer Death Risk Assessment Tool, and PLCOm2012) with varying risk thresholds for eligibility (risk model–based strategies). A total of 1,093 (289 risk factor–based and 804 risk model–based) strategies were evaluated. Full uptake and adherence for all scenarios were assumed. Main Outcomes and Measures Benefits: Lung cancer deaths averted and LYG compared with no screening per 100,000 population. Harms: Lifetime number of LDCT screens, false-positive results, biopsies, overdiagnosed cases, and radiation-related lung cancer deaths per 100,000 population. Results We identified a set of LDCT screening programs that are efficient and result in the most lung cancer deaths averted and LYG for a given level of screening (number of LDCT screens). Most efficient risk factor–based strategies start screening at age 50 or 55 years and stop screening at the age of 80 years. Most efficient risk factor–based strategies with at least 9 percent lung cancer mortality reduction have 20 pack-years as the minimum criterion for eligibility. The 2013 USPSTF-recommended criteria, which was selected based on lung cancer deaths averted using the 1950 birth cohort, is not among the efficient strategies for the 1960 birth cohort when considering both lung cancer deaths averted and LYG. However, annual strategies with the 20 pack-years minimum criterion, starting age of 50 or 55 years and stopping age of 80 years are efficient and result in increased screening eligibility (20.6% to 23.6% eligible) and considerably more lung cancer deaths averted (469 to 558 per 100,000) and LYG (6,018 to 7,596 per 100,000) than the 2013 USPSTF-recommended strategy (14.1% eligible, 381 lung cancer deaths averted and 4,882 LYG per 100,000). However these strategies also result in more false-positive tests (1.9 to 2.5 vs. 1.9 per person screened), overdiagnosed cases (83 to 94 vs. 69 per 100,000), and radiation-related lung cancer deaths (29.0 to 42.5 vs. 20.6 per 100,000) than the 2013 USPSTF-recommended strategy. The 20 pack-year strategies result in higher relative increases vs. the 2013 USPSTF-recommended criteria in eligibility, lung cancer deaths prevented, and LYG for women than men. These strategies also result in higher relative increases compared with the 2013 USPSTF-recommended criteria in eligibility for non-Hispanic blacks, Hispanics, and American Indian/Alaska Natives than for non-Hispanic whites and Asians. Among risk model–based screening strategies, the net benefits and harms of screening strongly depend on the risk model’s specific risk thresholds. Risk model–based vs. risk factor–based strategies result in higher numbers of lung cancer deaths prevented and modest additional LYGs and induce fewer radiation-related lung cancer deaths; however, they result in more overdiagnosed cases. The general patterns observed for the 1960 birth cohort for men and women combined hold for each sex and for the 1950 birth cohort. Limitations Simulations assumed 100 percent screening uptake and adherence. Relative performance of compared strategies might change if uptake and adherence differ by age or screening frequency. The models extrapolated results from short-term randomized trials with three LDCT annual screens to lifetime screening and followup. Simulations did not consider incidental findings and were restricted to the 1950 and 1960 U.S. birth cohorts. Conclusions and Relevance This collaborative modeling analysis suggests that LDCT screening could lead to important reductions of lung cancer mortality and result in significant LYG when optimally targeted. In particular, screening individuals ages 50 or 55 years through 80 years with 20 or more pack-years of smoking exposure would result in more benefits than current criteria and would reduce disparities in eligibility by sex and race/ethnicity. Risk model–based screening strategies could result in higher benefits compared with risk factor–based screening strategies; however, the analysis did not consider issues of implementation and other potential challenges of risk model–based screening strategies.

Updated Methodology for Projecting U.S.- and State-Level Cancer Counts for the Current Calendar Year: Part II: Evaluation of Incidence and Mortality Projection Methods.

Abstract: Background: The American Cancer Society (ACS) and the NCI collaborate every 5 to 8 years to update the methods for estimating the numbers of new cancer cases and deaths in the current year for the U.S. and individual states. Herein, we compare our current projection methodology with the next generation of statistical models. Methods: A validation study was conducted comparing current projection methods (vector autoregression for incidence; Joinpoint regression for mortality) with the Bayes state-space method and novel Joinpoint algorithms. Incidence data from 1996–2010 were projected to 2014 using two inputs: modeled data and observed data with modeled where observed were missing. For mortality, observed data from 1995 to 2009, 1996 to 2010, 1997 to 2011, and 1998 to 2012, each projected 3 years forward to 2012 to 2015. Projection methods were evaluated using the average absolute relative deviation (AARD) between observed counts (2014 for incidence, 2012–2015 for mortality) and estimates for 47 cancer sites nationally and 21 sites by state. Results: A novel Joinpoint model provided a good fit for both incidence and mortality, particularly for the most common cancers in the U.S. Notably, the AARD for cancers with cases in 2014 exceeding 49,000 for this model was 3.4%, nearly half that of the current method (6.3%). Conclusions: A data-driven Joinpoint algorithm had versatile performance at the national and state levels and will replace the ACS9s current methods. Impact: This methodology provides estimates of cancer data that are not available for the current year, thus continuing to fill an important gap for advocacy, research, and public health planning.

Inference about age-standardized rates with sampling errors in the denominators.

Abstract: Cancer incidence and mortality are typically presented as age-standardized rates. Inference about these rates becomes complicated when denominators involve sampling errors. We propose a bias-corrected rate estimator as well as its corresponding variance estimator that take into account sampling errors in the denominators. Confidence intervals are derived based on the proposed estimators as well. Performance of the proposed methods is evaluated empirically based on simulation studies. More importantly, advantage of the proposed method is demonstrated and verified in a real-life study of cancer mortality disparity. A web-based, user-friendly computational tool is also being developed at the National Cancer Institute to accompany the new methods with the first application being calculating cancer mortality rates by US-born and foreign-born status. Finally, promise of proposed estimators to account for errors introduced by differential privacy procedures to the 2020 decennial census products is discussed.

Updated Methodology for Projecting U.S.- and State-Level Cancer Counts for the Current Calendar Year: Part I: Spatio-temporal Modeling for Cancer Incidence.

Abstract: Background: The American Cancer Society (ACS) and the NCI collaborate every 5–8 years to update the methods for estimating numbers of new cancer cases and deaths in the current year in the United States and in every state and the District of Columbia. In this article, we reevaluate the statistical method for estimating unavailable historical incident cases which are needed for projecting the current year counts. Methods: We compared the current county-level model developed in 2012 (M0) with three new models, including a state-level mixed effect model (M1) and two state-level hierarchical Bayes models with varying random effects (M2 and M3). We used 1996–2014 incidence data for 16 sex-specific cancer sites to fit the models. An average absolute relative deviation (AARD) comparing the observed with the model-specific predicted counts was calculated for each site. Models were also cross-validated for six selected sex-specific cancer sites. Results: For the cross-validation, the AARD ranged from 2.8% to 33.0% for M0, 3.3% to 31.1% for M1, 6.6% to 30.5% for M2, and 10.4% to 393.2% for M3. M1 encountered the least technical issues in terms of model convergence and running time. Conclusions: The state-level mixed effect model (M1) was overall superior in accuracy and computational efficiency and will be the new model for the ACS current year projection project. Impact: In addition to predicting the unavailable state-level historical incidence counts for cancer surveillance, the updated algorithms have broad applicability for disease mapping and other activities of public health planning, advocacy, and research.

Characterizing Trends in Cancer Patients' Survival Using the JPSurv Software.

Abstract: Background: Improvements in cancer survival are usually assessed by comparing survival in grouped years of diagnosis. To enhance analyses of survival trends, we present the joinpoint survival model webtool (JPSurv) that analyzes survival data by single year of diagnosis and estimates changes in survival trends and year-over-year trend measures. Methods: We apply JPSurv to relative survival data for individuals diagnosed with female breast cancer, melanoma cancer, non–Hodgkin lymphoma (NHL), and chronic myeloid leukemia (CML) between 1975 and 2015 in the Surveillance, Epidemiology, and End Results Program. We estimate the number and location of joinpoints and the trend measures and provide interpretation. Results: In general, relative survival has substantially improved at least since the mid-1990s for all cancer sites. The largest improvements in 5-year relative survival were observed for distant-stage melanoma after 2009, which increased by almost 3 survival percentage points for each subsequent year of diagnosis, followed by CML in 1995–2010, and NHL in 1995–2003. The modeling also showed that for patients diagnosed with CML after 1995 (compared with before), there was a greater decrease in the probability of dying of the disease in the 4th and 5th years after diagnosis compared with the initial years since diagnosis. Conclusions: The greatest increases in trends for distant melanoma, NHL, and CML coincided with the introduction of novel treatments, demonstrating the value of JPSurv for estimating and interpreting cancer survival trends. Impact: The JPSurv webtool provides a suite of estimates for analyzing trends in cancer survival that complement traditional descriptive survival analyses.

Colorectal Cancer Screening: An Updated Decision Analysis for the U.S. Preventive Services Task Force

Abstract: Importance The U.S. Preventive Services Task Force (USPSTF) is updating its 2016 recommendations for screening for colorectal cancer. Objective To provide the USPSTF updated model-based estimates of the benefits, burden, and harms of colorectal cancer screening strategies that vary by the ages to begin and end screening, screening modality, and screening interval. Analyses also identify strategies that may provide an efficient balance of the colonoscopy burden and the life-years gained (LYG) from screening. Design Comparative modeling using 3 microsimulation models that simulate outcomes with and without colorectal cancer screening in a hypothetical cohort of previously unscreened average-risk U.S. 40-year-olds with no prior colorectal cancer diagnosis. Exposures Screening from ages 45, 50 or 55 years to ages 70, 75, 80, or 85 years with fecal immunochemical testing (FIT), multitarget stool DNA testing (FIT-DNA), flexible sigmoidoscopy (SIG) alone or in conjunction with interval FIT, computed tomographic colonography (CTC), or colonoscopy. Screening intervals varied by modality. All persons with an abnormal non-colonoscopy screening test were assumed to undergo follow up colonoscopy. Full adherence with all screening, follow up, and surveillance procedures was assumed. Main Outcome and Measures Estimated LYG relative to no screening (benefit), lifetime number of colonoscopies (burden), lifetime number of complications from screening (harms), and balance of incremental burden and benefit (efficiency ratios). Efficient strategies were those that required fewer additional colonoscopies per LYG, relative to other strategies. Results Estimated LYG from screening ranged from 171 to 381 per 1000 40-year-olds. Lifetime colonoscopy burden ranged from 624 to 6817 per 1000 individuals, and screening complications ranged from 5 to 22 per 1000 individuals. Forty-nine screening strategies were found to be efficient options by all 3 models; in 41 of these strategies, screening began at age 45. No single age to end screening was predominant among the efficient strategies, although the estimated increases in LYG from continuing screening after age 75 were generally small. With the exception of a 5-year interval for CTC, no screening interval was predominant among the efficient strategies for each modality. Among the screening strategies highlighted in the 2016 USPSTF colorectal cancer screening recommendations, lowering the age to begin screening from 50 to 45 was estimated to result in 22 to 27 additional LYG, 2 to 3 fewer colorectal cancer cases, and 0.9 to 1 fewer colorectal cancer death, but it was also estimated to result in 0.1 to 2 additional complications, 161 to 784 additional colonoscopies, and 0 (with colonoscopy) to 3553 additional non-colonoscopy tests over the lifetimes of 1000 persons (ranges are across screening strategies, based on mean estimates across the 3 models). Sensitivity analyses indicated that there was little advantage to customizing screening by race and sex; the estimated numbers of LYG, colonoscopies, and complications were similar across race-sex groups, as were the efficient strategies and their ratios. Scenario analyses demonstrated that efficient strategies were similar across 3 scenarios for the population risk of colorectal cancer, including one in which the assumed risk increase was less conservative than the assumption for the base-case analysis. The effect of imperfect adherence on outcomes was estimated by comparing strategies with different ages to begin screening (to examine delays in uptake) or with strategies with different screening intervals (to examine delays in rescreening). For example, the models estimated that extending the interval of repeat colonoscopy screening from 10 to 15 years would result in a loss of 22 to 38 life years per 1000, and extending the interval of FIT screening from annual to triennial testing would result in a loss of 28 to 41 life years per 1000. Limitations The models do not simulate the serrated polyp pathway to CRC. The models assume that the observed increase in colorectal cancer incidence among 20- to 44-year-olds in recent years is a cohort effect, and that the increase in risk will be carried forward as individuals age. They further assume that the increase in incidence is driven by an increased risk of developing adenomas, as opposed to faster or more frequent progression of adenomas to malignancy. Conclusions This comparative modeling study suggests that colorectal cancer screening may lead to sizable reductions in the lifetime risks of developing and dying from colorectal cancer. Many screening strategies are estimated to provide an efficient balance of the burden and benefit of screening; these strategies encompass a range of screening modalities, intervals, and ages. However, when the benefits of screening are measured by the number of LYG, most of the efficient screening strategies identified by all 3 models specified screening starting at age 45. Starting screening at age 45 was generally estimated to result in more LYG and fewer colorectal cancer cases and deaths than similar strategies with screening starting at age 50 or age 55, albeit with a higher lifetime burden of both colonoscopy and non-colonoscopy testing and slightly higher lifetime risks of complications.