Ruth Etzioni

Fred Hutchinson Cancer Research Center, Seattle, Washington, United States

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Publications (114)884.13 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: The frequency of overdiagnosis associated with breast cancer screening is a topic of controversy. Published estimates vary widely, but identifying which estimates are reliable is challenging. In this article we present an approach that provides a check on these estimates. Our approach leverages the close link between overdiagnosis and lead time by identifying the average lead time most consistent with a given overdiagnosis frequency. We consider a high-profile study that suggested that 31% of breast cancers diagnosed in the United States in 2008 were overdiagnosed and show that this corresponds to an average lead time of about nine years among localized cases. Comparing this estimate with the average lead time for invasive, screen-detected breast cancers of 40 months, around which there is a relative consensus, suggests the published estimate of overdiagnosis is excessive. This approach provides a novel way to appraise estimates of overdiagnosis given knowledge of disease natural history.
    Journal of the National Cancer Institute. 12/2014; 106(12).
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    ABSTRACT: Although American Society of Clinical Oncology guidelines discourage the use of tumor marker assessment for routine surveillance in nonmetastatic breast cancer, their use in practice is uncertain. Our objective was to determine use of tumor marker tests such as carcinoembryonic antigen and CA 15-3/CA 27.29 and associated Medicare costs in early-stage breast cancer survivors.
    Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 10/2014;
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    ABSTRACT: Prostate-specific antigen recurrence (PSA-R) after radical prostatectomy (RP) can occur years before metastasis. This study estimates the chance that an untreated PSA-R would not progress to clinical metastasis within the patient's lifetime, that is, that recurrence is overdetected.
    Clinical cancer research : an official journal of the American Association for Cancer Research. 10/2014; 20(20):5302-10.
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    ABSTRACT: Factors affecting the adoption of non-curative initial management (NCIM) in the United States for low-risk prostate cancer (PCa) on a population-based level are unknown. Our objectives were to measure temporal trends in the proportion of low- and intermediate-risk PCa patients electing NCIM in the US and analyze the association of factors affecting management choice.
    The Journal of urology. 08/2014;
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    ABSTRACT: Harms and benefits of cancer screening depend on age and comorbid conditions, but reliable estimates are lacking.
    Annals of internal medicine 07/2014; 161(2):104-12. · 13.98 Impact Factor
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    ABSTRACT: BACKGROUND Prostate-specific antigen (PSA) screening for prostate cancer has high risks of overdiagnosis, particularly among older men, and reports from screening trials indicate that it saves few lives after 11 to 13 years of follow-up. New clinical guidelines recommend against PSA screening for all men or for men aged >70 years, but, to the authors' knowledge, the expected population effects of these guidelines have not been studied to date.METHODS Two models of prostate cancer natural history and diagnosis were previously developed using reconstructed PSA screening patterns and prostate cancer incidence in the United States. Assuming a survival benefit of PSA screening consistent with the screening trials, the authors used the models to predict incidence and mortality rates for the period from 2013 through 2025 under continued PSA screening and under discontinued PSA screening for all men or for men aged >70 years.RESULTSThe models predicted that continuation of recent screening rates will overdiagnose 710,000 to 1,120,000 men (range between models) but will avoid 36,000 to 57,000 cancer deaths over the period 2013 through 2025. Discontinued screening for all men eliminated 100% of overdiagnoses but failed to prevent 100% of avoidable cancer deaths. Continued screening for men aged <70 years eliminated 64% to 66% of overdiagnoses but failed to prevent 36% to 39% of avoidable cancer deaths.CONCLUSIONS Discontinuing PSA screening for all men may generate many avoidable cancer deaths. Continuing PSA screening for men aged <70 years could prevent greater than one-half of these avoidable cancer deaths while dramatically reducing overdiagnoses compared with continued PSA screening for all ages. Cancer 2014. © 2014 American Cancer Society.
    Cancer 07/2014; · 5.20 Impact Factor
  • Ruth Etzioni, Roman Gulati
    Journal of General Internal Medicine 05/2014; · 3.28 Impact Factor
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    ABSTRACT: The findings of the Women's Health Initiative (WHI) estrogen plus progestin (E+P) trial led to a substantial reduction in use of combined hormone therapy (cHT) among postmenopausal women in the United States. The economic effect of this shift has not been evaluated relative to the trial's $260 million cost (2012 U.S. dollars). To estimate the economic return from the WHI E+P trial. Decision model to simulate health outcomes for a "WHI scenario" with observed cHT use and a "no-WHI scenario" with cHT use extrapolated from the pretrial period. Primary analyses of WHI outcomes, peer-reviewed literature, and government sources. Postmenopausal women in the United States, aged 50 to 79 years, who did not have a hysterectomy. 2003 to 2012. Payer. Combined hormone therapy. Disease incidence, expenditure, quality-adjusted life-years, and net economic return. The WHI scenario resulted in 4.3 million fewer cHT users, 126 000 fewer breast cancer cases, 76 000 fewer cardiovascular disease cases, 263 000 more fractures, 145 000 more quality-adjusted life-years, and expenditure savings of $35.2 billion. The corresponding net economic return of the trial was $37.1 billion ($140 per dollar invested in the trial) at a willingness-to-pay level of $100 000 per quality-adjusted life-year. The 95% CI for the net economic return of the trial was $23.1 to $51.2 billion. No evaluation of indirect costs or outcomes beyond 2012. The WHI E+P trial made high-value use of public funds with a substantial return on investment. These results can contribute to discussions about the role of public funding for large, prospective trials with high potential for public health effects. National Heart, Lung, and Blood Institute.
    Annals of internal medicine 05/2014; 160(9):594-602. · 13.98 Impact Factor
  • Ruth D Etzioni, Ian M Thompson
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    ABSTRACT: Publication of apparently conflicting results from 2 large trials of prostate cancer screening has intensified the debate about prostate-specific antigen (PSA) testing and has led to a recommendation against screening from the US Preventive Services Task Force. This article reviews the trials and discusses the limitations of their empirical results in informing public health policy. In particular, the authors explain why harm-benefit trade-offs based on empirical results may not accurately reflect the trade-offs expected under long-term population screening. This information should be useful to clinicians in understanding the implications of these studies regarding the value of PSA screening.
    Urologic Clinics of North America 05/2014; 41(2):223-228. · 1.39 Impact Factor
  • Ruth Etzioni, Roman Gulati
    CancerSpectrum Knowledge Environment 03/2014; · 14.07 Impact Factor
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    ABSTRACT: Clinical trials test the efficacy of a treatment in a select patient population. We examined whether cancer clinical trial patients were similar to nontrial, "real-world" patients with respect to presenting characteristics and survival. We reviewed the SWOG national clinical trials consortium database to identify candidate trials. Demographic factors, stage, and overall survival for patients in the standard arms were compared with nontrial control subjects selected from the Surveillance, Epidemiology, and End Results program. Multivariable survival analyses using Cox regression were conducted. The survival functions from aggregate data across all studies were compared separately by prognosis (≥50% vs <50% average 2-year survival). All statistical tests were two-sided. We analyzed 21 SWOG studies (11 good prognosis and 10 poor prognosis) comprising 5190 patients enrolled from 1987 to 2007. Trial patients were younger than nontrial patients (P < .001). In multivariable analysis, trial participation was not associated with improved overall survival for all 11 good-prognosis studies but was associated with better survival for nine of 10 poor-prognosis studies (P < .001). The impact of trial participation on overall survival endured for only 1 year. Trial participation was associated with better survival in the first year after diagnosis, likely because of eligibility criteria that excluded higher comorbidity patients from trials. Similar survival patterns between trial and nontrial patients after the first year suggest that trial standard arm outcomes are generalizable over the long term and may improve confidence that trial treatment effects will translate to the real-world setting. Reducing eligibility criteria would improve access to clinical trials.
    CancerSpectrum Knowledge Environment 03/2014; · 14.07 Impact Factor
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    ABSTRACT: In the United States, more men with prostate cancer are being diagnosed with prostate-specific antigen <10 ng/ml and stage cT1-cT2a; however, fewer are diagnosed with Gleason score 6 (likely due to 2005 changes in Gleason grading), which limits the number of men eligible for active surveillance.
    European Urology 03/2014; · 10.48 Impact Factor
  • Ruth Etzioni
    European Urology 02/2014; · 10.48 Impact Factor
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    ABSTRACT: Prostate-specific antigen (PSA) screening for prostate cancer may reduce mortality, but it incurs considerable risk of overdiagnosis and potential harm to quality of life. Our objective was to evaluate the cost-effectiveness of PSA screening, with and without adjustment for quality of life, for the British Columbia (BC) population. We adapted an existing natural history model using BC incidence, treatment, cost and mortality patterns. The modeled mortality benefit of screening derives from a stage-shift mechanism, assuming mortality reduction consistent with the European Study of Randomized Screening for Prostate Cancer. The model projected outcomes for 40 year-old men under 14 combinations of screening ages and frequencies. Cost and utility estimates were explored with deterministic sensitivity analysis. The incremental cost-effectiveness of regular screening ranged from $36,300/LYG, for screening every four years from ages 55-69, to $588,300/LYG, for screening every two years from ages 40-74. The marginal benefits of increasing screening frequency to two years or starting screening at age 40 were small and came at significant cost. After utility adjustment, all screening strategies resulted in a loss of QALYs; however, this result was very sensitive to utility estimates. Plausible outcomes under a range of screening strategies inform discussion of prostate cancer screening policy in BC and similar jurisdictions. Screening may be cost-effective but the sensitivity of results to utility values suggests individual preferences for quality versus quantity of life should be a key consideration. © 2014 Wiley Periodicals, Inc.
    International Journal of Cancer 01/2014; · 6.20 Impact Factor
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    ABSTRACT: Although prostate cancer (PCa) screening reduces the incidence of advanced disease and mortality, trade-offs include overdiagnosis and resultant overtreatment. To review primary data on PCa overdiagnosis and overtreatment. Electronic searches were conducted in Cochrane Central Register of Controlled Trials, PubMed, and Embase from inception to July 2013 for original articles on PCa overdiagnosis and overtreatment. Supplemental articles were identified through hand searches. The lead-time and excess-incidence approaches are the main ways used to estimate overdiagnosis in epidemiological studies, with estimates varying widely. The estimated number of PCa cases needed to be diagnosed to save a life has ranged from 48 down to 5 with increasing follow-up. In clinical studies, generally lower rates of overdiagnosis have been reported based on the frequency of low-grade minimal tumors at radical prostatectomy (1.7-46.8%). Autopsy studies have reported PCa in 18.5-38.5%, although not all are low grade or low volume. Factors influencing overdiagnosis include the study population, screening protocol, and background incidence, limiting generalizability between settings. Reported rates of overtreatment vary widely in the literature, although contemporary international studies suggest increasing use of conservative management. Epidemiological, clinical, and autopsy studies have been used to examine PCa overdiagnosis, with estimates ranging widely from 1.7% to 67%. Correspondingly, estimates of overtreatment vary widely based on patient features and may be declining internationally. Careful patient selection for screening and reducing overtreatment are important to preserve the benefits and reduce the downstream harms of prostate-specific antigen testing. Because all of these estimates are extremely population and context specific, this must be considered when using these data to inform policy. Screening reduces spread and death from prostate cancer (PCa) but overdiagnoses some low-risk tumors that may not have caused harm. Because treatment has potential side effects, it is critical that not all patients with PCa receive aggressive treatment.
    European Urology 01/2014; · 10.48 Impact Factor
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    ABSTRACT: The chance that a prostate cancer detected by screening is overdiagnosed (ie, it would not have been detected in the absence of screening) can vary widely depending on the patient's age and tumor characteristics. The purpose of this study is to use age, Gleason score, and prostate-specific antigen (PSA) level to help inform patients with screen-detected prostate cancers about the chances their cancers were overdiagnosed. A computer microsimulation model of prostate cancer natural history was used to generate virtual life histories in the presence and absence of PSA screening, including an indicator of whether screen-detected cancers are overdiagnosed. A logistic regression model was fit to nonmetastatic patients diagnosed by screening with PSA less than 10ng/mL, and a nomogram was created to predict the individualized risk of overdiagnosis given age, Gleason score, and PSA at diagnosis. The calibrated microsimulation model closely reproduces observed incidence trends in the Surveillance, Epidemiology, and End Results registries by age, stage, and Gleason score. The fitted logistic regression predicts risks of overdiagnosis among PSA-detected patients with an area under the curve of 0.75. Chances of overdiagnosis range from 2.9% to 88.1%. The chances of overdiagnosis vary considerably by age, Gleason score, and PSA at diagnosis. The overdiagnosis nomogram presents tailored estimates of these risks based on patient and tumor information known at diagnosis and can be used to inform decisions about treating PSA-detected prostate cancers.
    CancerSpectrum Knowledge Environment 01/2014; · 14.07 Impact Factor
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    ABSTRACT: Prostate cancer grade, assessed with the Gleason score, describes how abnormal the tumor tissue and cells appear, and it is an important prognostic indicator of disease progression. Whether prostate tumors change grade is a question that has implications for screening and treatment. Empirical data on tumor grade over time have become available from men biopsied regularly as part of active surveillance (AS). However, biopsy (BX) grade is subject to misclassification. In this article, we develop a model that allows for estimation of the time of grade change while accounting for the misclassification error from BX grade. We use misclassification rates from studies of prostate cancer BXs followed by radical prostatectomy. Estimation of the transition times from true low-grade to high-grade disease is conducted within a Bayesian framework. We apply our model to serial observations on BX grade among 627 cases enrolled in a cohort of AS patients at Johns Hopkins University who were biopsied annually and referred to treatment if there was any evidence of disease progression on BX. We consider different prior distributions for the time to true grade progression. The estimated likelihood of grade progression within 10 years of study entry ranges from 12% to 24% depending on the prior. We conclude that knowledge of rates of grade misclassification allows for determination of true grade progression rates among men with serial BXs on AS. Although our results are sensitive to prior specifications, they indicate that in a nontrivial fraction of the patient population, tumor grade can progress. Copyright © 2013 John Wiley & Sons, Ltd.
    Statistics in Medicine 10/2013; · 2.04 Impact Factor
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    ABSTRACT: Although surrogate measures of benign prostatic hyperplasia (BPH) are often used in epidemiologic studies, their performance characteristics are unknown. Using data from the Prostate Cancer Prevention Trial (n = 5,986), we evaluated prostate-specific antigen (PSA), International Prostate Symptom Score (IPSS), and their rates of change as predictors of incident BPH. BPH (n = 842 cases) was defined as medical or surgical treatment or at least 2 IPSS of 15 or higher. Proportional hazards models were used to measure the associations of baseline PSA, IPSS, and their velocities over 2 years with BPH risk, and time-dependent receiver-operating characteristic curves were used to measure their discriminatory performance. Unit increases in PSA, IPSS, and IPSS velocity were associated with 34%, 35%, and 29% (all P < 0.001) increases in BPH risk, respectively. The areas under the receiver-operating characteristic curves were significantly greater than 0.5 for PSA (0.58, 95% confidence interval (CI): 0.56, 0.60), IPSS (0.77, 95% CI: 0.75, 0.78), and IPSS velocity (0.63, 95% CI: 0.61, 0.65); however there were no cut points at which sensitivity and specificity were both above 75%. We concluded that moderate elevations in PSA, IPSS, or their rates of change should not be used as surrogate measures of incident BPH.
    American journal of epidemiology 06/2013; · 5.59 Impact Factor
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    ABSTRACT: Knowledge of the likelihood that a screening-detected case of cancer has been overdiagnosed is vitally important to make treatment decisions and develop screening policy. An overdiagnosed case is an excess case detected by screening. Estimates of the frequency of overdiagnosis in breast and prostate cancer screening vary greatly across studies. This article identifies features of overdiagnosis studies that influence results and shows their effect by using published research. First, different ways to define and measure overdiagnosis are considered. Second, contextual features and how they affect overdiagnosis estimates are examined. Third, the effect of estimation approach is discussed. Many studies use excess incidence under screening as a proxy for overdiagnosis. Others use statistical models to make inferences about lead time or natural history and then derive the corresponding fraction of cases that are overdiagnosed. This article concludes with questions that readers of overdiagnosis studies can use to evaluate the validity and relevance of published estimates and recommends that authors of studies quantifying overdiagnosis provide information about these features.
    Annals of internal medicine 06/2013; 158(11):831-8. · 13.98 Impact Factor
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    ABSTRACT: Because receipt of breast imaging likely occurs in nonrandom patterns, selection bias is an important issue in studies that attempt to elucidate associations between imaging and breast cancer outcomes. The purpose of this study was to analyze use of advanced diagnostic imaging in a cohort of patients with breast cancer insured by commercial, managed care, and public health plans by demographic, health insurance, and clinical variables from 2002 to 2009. We identified women with breast cancer diagnoses from a Surveillance Epidemiology and End Results (SEER) registry whose data could be linked to claims from participating health plans. We examined imaging that occurred between cancer diagnosis and initiation of treatment and classified patients according to receipt of (1) mammography or ultrasound only; (2) breast magnetic resonance imaging (MRI); and (3) other advanced imaging (computed tomography [CT] of the chest, abdoment, and pelvis; positron emission tomography [PET]; or PET-CT). We used logistic regression to identify factors associated with receipt of breast MRI as well as other advanced imaging. Commercial health plan, younger age, and later year of diagnosis were strongly associated with receipt of breast MRI and other advanced imaging. Women with prescription drug plans and those who had less comorbidities were more likely to have received breast MRI. Use of breast MRI and other advanced imaging is increasing among patients newly diagnosed with breast cancer; individual patient and insurance-related factors are associated with receipt of these imaging tests. Whether use of diagnostic advanced imaging affects outcomes such as re-excision, cancer recurrence, mortality rates, and costs of breast cancer treatment remains to be determined.
    Journal of Oncology Practice 05/2013;

Publication Stats

3k Citations
884.13 Total Impact Points


  • 1998–2014
    • Fred Hutchinson Cancer Research Center
      • • Division of Public Health Sciences
      • • Biostatistics and Biomathematics Program
      Seattle, Washington, United States
  • 2013
    • Memorial Sloan-Kettering Cancer Center
      New York City, New York, United States
    • University of Texas Health Science Center at Houston
      • Medical School
      Houston, TX, United States
  • 2002–2013
    • University of Washington Seattle
      • • Department of Biostatistics
      • • Department of Statistics
      • • Department of Epidemiology
      Seattle, Washington, United States
  • 2010–2012
    • U.S. Department of Veterans Affairs
      • Health Services Research and Development Service ( HSR&D)
      Washington, D. C., DC, United States
  • 2011
    • VA Puget Sound Health Care System
      Washington, Washington, D.C., United States
  • 2009
    • National Institute of Allergy and Infectious Diseases
      Maryland, United States
  • 2007
    • National Institutes of Health
      • Division of Cancer Control and Population Sciences
      Bethesda, MD, United States
  • 1998–2002
    • National Cancer Institute (USA)
      • • Division of Cancer Control and Population Sciences
      • • Applied Research Program (ARP)
      Bethesda, MD, United States