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Comparative effectiveness of alternative prostate-specific antigen--based prostate cancer screening strategies: model estimates of potential benefits and harms.

ABSTRACT: The U.S. Preventive Services Task Force recently concluded that the harms of existing prostate-specific antigen (PSA) screening strategies outweigh the benefits.To evaluate comparative effectiveness of alternative PSA screening strategies.Microsimulation model of prostate cancer incidence and mortality quantifying harms and lives saved for alternative PSA screening strategies.National and trial data on PSA growth, screening and biopsy patterns, incidence, treatment distributions, treatment efficacy, and mortality.A contemporary cohort of U.S. men.Lifetime.Societal.35 screening strategies that vary by start and stop ages, screening intervals, and thresholds for biopsy referral.PSA tests, false-positive test results, cancer detected, overdiagnoses, prostate cancer deaths, lives saved, and months of life saved.Without screening, the risk for prostate cancer death is 2.86%. A reference strategy that screens men aged 50 to 74 years annually with a PSA threshold for biopsy referral of 4 µg/L reduces the risk for prostate cancer death to 2.15%, with risk for overdiagnosis of 3.3%. A strategy that uses higher PSA thresholds for biopsy referral in older men achieves a similar risk for prostate cancer death (2.23%) but reduces the risk for overdiagnosis to 2.3%. A strategy that screens biennially with longer screening intervals for men with low PSA levels achieves similar risks for prostate cancer death (2.27%) and overdiagnosis (2.4%), but reduces total tests by 59% and false-positive results by 50%.Varying incidence inputs or reducing the survival improvement due to screening did not change conclusions.The model is a simplification of the natural history of prostate cancer, and improvement in survival due to screening is uncertain.Compared with standard screening, PSA screening strategies that use higher thresholds for biopsy referral for older men and that screen men with low PSA levels less frequently can reduce harms while preserving lives.National Cancer Institute and Centers for Disease Control and Prevention.

SUBMITTER: Gulati R

PROVIDER: S-EPMC3738063 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature

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Comparative effectiveness of alternative prostate-specific antigen--based prostate cancer screening strategies: model estimates of potential benefits and harms.

Gulati Roman R Gore John L JL Etzioni Ruth R

Annals of internal medicine 20130201 3

<h4>Background</h4>The U.S. Preventive Services Task Force recently concluded that the harms of existing prostate-specific antigen (PSA) screening strategies outweigh the benefits.<h4>Objective</h4>To evaluate comparative effectiveness of alternative PSA screening strategies.<h4>Design</h4>Microsimulation model of prostate cancer incidence and mortality quantifying harms and lives saved for alternative PSA screening strategies.<h4>Data sources</h4>National and trial data on PSA growth, screening ...[more]

PMID: 23381039

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Project description:BackgroundThe optimum screening policy for lung cancer is unknown.ObjectiveTo identify efficient computed tomography (CT) screening scenarios in which relatively more lung cancer deaths are averted for fewer CT screening examinations.DesignComparative modeling study using 5 independent models.Data sourcesThe National Lung Screening Trial; the Prostate, Lung, Colorectal, and Ovarian Cancer Screening trial; the Surveillance, Epidemiology, and End Results program; and the U.S. Smoking History Generator.Target populationU.S. cohort born in 1950.Time horizonCohort followed from ages 45 to 90 years.PerspectiveSocietal.Intervention576 scenarios with varying eligibility criteria (age, pack-years of smoking, years since quitting) and screening intervals.Outcome measuresBenefits included lung cancer deaths averted or life-years gained. Harms included CT examinations, false-positive results (including those obtained from biopsy/surgery), overdiagnosed cases, and radiation-related deaths.Results of best-case scenarioThe most advantageous strategy was annual screening from ages 55 through 80 years for ever-smokers with a smoking history of at least 30 pack-years and ex-smokers with less than 15 years since quitting. It would lead to 50% (model ranges, 45% to 54%) of cases of cancer being detected at an early stage (stage I/II), 575 screening examinations per lung cancer death averted, a 14% (range, 8.2% to 23.5%) reduction in lung cancer mortality, 497 lung cancer deaths averted, and 5250 life-years gained per the 100,000-member cohort. Harms would include 67,550 false-positive test results, 910 biopsies or surgeries for benign lesions, and 190 overdiagnosed cases of cancer (3.7% of all cases of lung cancer [model ranges, 1.4% to 8.3%]).Results of sensitivity analysisThe number of cancer deaths averted for the scenario varied across models between 177 and 862; the number of overdiagnosed cases of cancer varied between 72 and 426.LimitationsScenarios assumed 100% screening adherence. Data derived from trials with short duration were extrapolated to lifetime follow-up.ConclusionAnnual CT screening for lung cancer has a favorable benefit-harm ratio for individuals aged 55 through 80 years with 30 or more pack-years' exposure to smoking.Primary funding sourceNational Cancer Institute.

Project description:BACKGROUND:Controversy persists about optimal mammography screening strategies. OBJECTIVE:To evaluate screening outcomes, taking into account advances in mammography and treatment of breast cancer. DESIGN:Collaboration of 6 simulation models using national data on incidence, digital mammography performance, treatment effects, and other-cause mortality. SETTING:United States. PATIENTS:Average-risk U.S. female population and subgroups with varying risk, breast density, or comorbidity. INTERVENTION:Eight strategies differing by age at which screening starts (40, 45, or 50 years) and screening interval (annual, biennial, and hybrid [annual for women in their 40s and biennial thereafter]). All strategies assumed 100% adherence and stopped at age 74 years. MEASUREMENTS:Benefits (breast cancer-specific mortality reduction, breast cancer deaths averted, life-years, and quality-adjusted life-years); number of mammograms used; harms (false-positive results, benign biopsies, and overdiagnosis); and ratios of harms (or use) and benefits (efficiency) per 1000 screens. RESULTS:Biennial strategies were consistently the most efficient for average-risk women. Biennial screening from age 50 to 74 years avoided a median of 7 breast cancer deaths versus no screening; annual screening from age 40 to 74 years avoided an additional 3 deaths, but yielded 1988 more false-positive results and 11 more overdiagnoses per 1000 women screened. Annual screening from age 50 to 74 years was inefficient (similar benefits, but more harms than other strategies). For groups with a 2- to 4-fold increased risk, annual screening from age 40 years had similar harms and benefits as screening average-risk women biennially from 50 to 74 years. For groups with moderate or severe comorbidity, screening could stop at age 66 to 68 years. LIMITATION:Other imaging technologies, polygenic risk, and nonadherence were not considered. CONCLUSION:Biennial screening for breast cancer is efficient for average-risk populations. Decisions about starting ages and intervals will depend on population characteristics and the decision makers' weight given to the harms and benefits of screening. PRIMARY FUNDING SOURCE:National Institutes of Health.

Project description:BackgroundSurveillance with annual mammography and breast magnetic resonance imaging (MRI) is recommended for female survivors of childhood cancer treated with chest radiation, yet benefits, harms, and costs are uncertain.ObjectiveTo compare the benefits, harms, and cost-effectiveness of breast cancer screening strategies in childhood cancer survivors.DesignCollaborative simulation modeling using 2 Cancer Intervention and Surveillance Modeling Network breast cancer models.Data sourcesChildhood Cancer Survivor Study and published data.Target populationWomen aged 20 years with a history of chest radiotherapy.Time horizonLifetime.PerspectivePayer.InterventionAnnual MRI with or without mammography, starting at age 25, 30, or 35 years.Outcome measuresBreast cancer deaths averted, false-positive screening results, benign biopsy results, and incremental cost-effectiveness ratios (ICERs).Results of base-case analysisLifetime breast cancer mortality risk without screening was 10% to 11% across models. Compared with no screening, starting at age 25 years, annual mammography with MRI averted the most deaths (56% to 71%) and annual MRI (without mammography) averted 56% to 62%. Both strategies had the most screening tests, false-positive screening results, and benign biopsy results. For an ICER threshold of less than $100 000 per quality-adjusted life-year gained, screening beginning at age 30 years was preferred.Results of sensitivity analysisAssuming lower screening performance, the benefit of adding mammography to MRI increased in both models, although the conclusions about preferred starting age remained unchanged.LimitationElevated breast cancer risk was based on survivors diagnosed with childhood cancer between 1970 and 1986.ConclusionEarly initiation (at ages 25 to 30 years) of annual breast cancer screening with MRI, with or without mammography, might reduce breast cancer mortality by half or more in survivors of childhood cancer.Primary funding sourceAmerican Cancer Society and National Institutes of Health.

Project description:BackgroundWhile polygenic risk scores (PRS) could enable the streamlining of organised cancer screening programmes, its current discriminative ability is limited. We conducted a cost-effectiveness analysis to trade-off the benefits and harms of PRS-stratified cancer screening in China.MethodsThe validated National Cancer Center (NCC) modelling framework for six cancers (lung, liver, breast, gastric, colorectum, and oesophagus) was used to simulate cancer incidence, progression, stage-specific cancer detection, and risk of death. We estimated the number of cancer deaths averted, quality-adjusted life-years (QALY) gained, number needed to screen (NNS), overdiagnosis, and incremental cost-effectiveness ratio (ICER) of one-time PRS-stratified screening strategy (screening 25% of PRS-defined high-risk population) for a birth cohort at age 60 in 2025, compared with unstratified screening strategy (screening 25% of general population) and no screening strategy. We applied lifetime horizon, societal perspective, and 3% discount rate. An ICER less than $18,364 per QALY gained is considered cost-effective.FindingsOne-time cancer screening for population aged 60 was the most cost-effective strategy compared to screening at other ages. Compared with an unstratified screening strategy, the PRS-stratified screening strategy averted more cancer deaths (61,237 vs. 40,329), had a lower NNS to prevent one death (307 vs. 451), had a slightly higher overdiagnosis (14.1% vs. 13.8%), and associated with an additional 130,045 QALYs at an additional cost of $1942 million, over a lifetime horizon. The ICER for all six cancers combined was $14,930 per QALY gained, with the ICER varying from $7928 in colorectal cancer to $39,068 in liver cancer. ICER estimates were sensitive to changes in risk threshold and cost of PRS tools.InterpretationPRS-stratified screening strategy modestly improves clinical benefit and cost-effectiveness of organised cancer screening programmes. Reducing the costs of polygenic risk stratification is needed before PRS implementation.FundingThe Chinese Academy of Medical Sciences, the Jing-jin-ji Special Projects for Basic Research Cooperation, and the Sanming Project of the Medicine in Shenzhen.

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Comparative effectiveness of alternative prostate-specific antigen--based prostate cancer screening strategies: model estimates of potential benefits and harms.

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Comparative effectiveness of alternative prostate-specific antigen--based prostate cancer screening strategies: model estimates of potential benefits and harms.

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