William J. Catalona, MD; Anthony V. D'Amico, MD; William F. Fitzgibbons, MD; Omofolasade Kosoko-Lasaki, MD; Stephen W. Leslie, MD; Henry T. Lynch, MD; Judd W. Moul, MD; Marc S. Rendell, MD; Patrick C. Walsh, MD
Potential Conflicts of Interest: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M12-0991.
Requests for Single Reprints: Marc S. Rendell, MD, The Creighton Diabetes Center, 601 North 30th Street, Omaha, NE 68131; e-mail, Rendell@asndi.com.
Current Author Addresses: Dr. Catalona: 675 North St. Clair Street, Suite 20-150, Chicago, IL 60611.
Dr. D'Amico: Brigham and Women's Hospital, 75 Francis Street #Asb1, Boston, MA 02115.
Dr. Fitzgibbons: Skyline Medical Center, 1908 North 203rd Street Suite 2, Elkhorn, NE 68022.
Dr. Kosoko-Lasaki: Health Sciences Office of Multicultural and Community Affairs, Hixson Lied Building, Suite L23, Creighton University, 2500 California Plaza, Omaha, NE 68178.
Dr. Leslie: Department of Surgery, Division of Urology, Suite 3700, 601 North 30th Street, Omaha, NE 68131.
Dr. Lynch: Hereditary Cancer Center and Department of Preventive Medicine, Creighton University, 2500 California Plaza, Omaha, NE 68178.
Dr. Moul: Division of Urologic Surgery, DUMC 3707-Room 1562 Duke South, Duke University Medical Center, Durham, NC 27705.
Dr. Rendell: The Creighton Diabetes Center, 601 North 30th Street, Omaha, NE 68131.
Dr. Walsh: Johns Hopkins Hospital, Park 224, Baltimore, MD 21287.
Author Contributions: Conception and design: W.J. Catalona, W.F. Fitzgibbons, J.W. Moul, M.S. Rendell, P.C. Walsh.
Analysis and interpretation of the data: W.J. Catalona, A.V. D'Amico, S.W. Leslie, H.T. Lynch, M.S. Rendell, P.C. Walsh.
Drafting of the article: W.J. Catalona, A.V. D'Amico, S.W. Leslie, J.W. Moul, M.S. Rendell, P.C. Walsh.
Critical revision of the article for important intellectual content: W.J. Catalona, A.V. D'Amico, W.F. Fitzgibbons, S.W. Leslie, J.W. Moul, M.S. Rendell, P.C. Walsh.
Final approval of the article: W.J. Catalona, A.V. D'Amico, W.F. Fitzgibbons, O. Kosoko-Lasaki, S.W. Leslie, H.T. Lynch, J.W. Moul, M.S. Rendell, P.C. Walsh.
Administrative, technical, or logistic support: S.W. Leslie, M.S. Rendell.
Collection and assembly of data: W.J. Catalona, A.V. D'Amico, S.W. Leslie.
Catalona W., D'Amico A., Fitzgibbons W., Kosoko-Lasaki O., Leslie S., Lynch H., Moul J., Rendell M., Walsh P.; What the U.S. Preventive Services Task Force Missed in Its Prostate Cancer Screening Recommendation. Ann Intern Med. 2012;157:137-138. doi: 10.7326/0003-4819-157-2-201207170-00463
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Published: Ann Intern Med. 2012;157(2):137-138.
The U.S. Preventive Services Task Force (USPSTF), a panel that does not include urologists or cancer specialists, has just recommended against prostate-specific antigen (PSA)–based screening for prostate cancer, stating that “screening may benefit a small number of men but will result in harm to many others” (1). Recognizing that prostate cancer remains the second-leading cause of cancer deaths in men, we, an ad hoc group that includes nationally recognized experts in the surgical and radiologic treatment of prostate cancer, oncologists, preventive medicine specialists, and primary care physicians, believe that the USPSTF has underestimated the benefits and overestimated the harms of prostate cancer screening. Therefore, we disagree with the USPSTF's recommendation.
The USPTSF bases its recommendation, in large part, on the 2 largest published randomized clinical trials (2). The U.S. PLCO (Prostate, Lung, Colorectal, and Ovarian) Cancer Screening Trial randomly assigned 76 685 men aged 55 to 74 years to receive either annual screening for 6 years or “usual care” (3). By 2009, 57% of the men had been followed for at least 13 years. The cumulative incidence rate for prostate cancer was slightly higher in the screened group, and prostate cancer mortality did not differ significantly between groups (3). The ERSPC (European Randomized Study of Screening for Prostate Cancer) randomly assigned 162 243 men aged 55 to 69 years to either PSA screening once every 4 years or an unscreened control group (4). After a median 11 years of follow-up, the cumulative incidence of prostate cancer was 8.2% in the screened group and 4.8% in the control group. Prostate cancer death was reduced by 21% in the screened group compared with the control group and 29% after adjustment for noncompliance (5). The Task Force concluded that this decrease in prostate cancer–specific mortality amounted to few lives saved and did not outweigh the harms of screening and diagnosis (false-positive results and associated anxiety and biopsy complications) and the harms related to the treatment of screen-detected cancer.
The Task Force's evidence review (2) did acknowledge strong evidence that treatment of localized prostate cancer reduced mortality compared with observation alone, citing a Scandinavian randomized, controlled trial with 15 years of follow-up showing that radical prostatectomy resulted in a sustained 38% decrease in prostate cancer–specific mortality (15% vs. 21%; risk ratio, 0.62 [95% CI, 0.44 to 0.87]) and 25% reduction in all-cause mortality (risk ratio, 0.75 [CI, 0.61 to 0.92]) (6). It also acknowledged other trials of surgery and radiation therapy showing an approximate 35% decrease in mortality. However, the Task Force's view was that perioperative events, urinary incontinence, and erectile dysfunction as complications of prostatectomy and bowel problems associated with radiation therapy must be considered, in addition to the mortality benefits of treatment.
We believe that in formulating its recommendation, the USPSTF either overlooked or misinterpreted the effect of significant methodological flaws in the 2 major clinical trials of screening. The most important flaws of the PLCO are the greater than 50% “contamination” rate by nonprotocol PSA measurements in the control group, prescreening of 40% of study participants before enrollment in the trial, and that two thirds of patients with abnormal screening tests did not have prompt biopsy (7). These issues, in our opinion, impair the claim that the PLCO is a true screening trial. In the ERSPC, compared with the PLCO, participants were younger, the PSA cutoff was lower, there was only approximately 15% “contamination,” and prompt biopsy was done far more frequently after positive PSA values. A secondary analysis of data from the Rotterdam site of the ERSPC that corrected for failure of participants to have protocol-prescribed screening procedures as well as contamination showed that PSA screening reduced the risk for dying of prostate cancer by as much as 31% (8).
A further limitation of both trials was having only a median follow-up of roughly 10 years, which we believe is inadequate for an often slowly progressive cancer. The Task Force gave little weight to the longer Göteborg Randomised Population-Based Prostate-Cancer Screening Trial (9), which had better protocol compliance and in which the interim 14-year median follow-up results showed a greater (44%) reduction in death from prostate cancer for the screened group (risk ratio, 0.56 [CI 0.39 to 0.82]; P = 0.002).
In addition to misinterpreting the potential effect of the limitations of the 2 largest screening trials, we believe that the Task Force had other flaws in its reasoning. First, it overlooked the fact that diagnostic procedures and related complications occur in unscreened populations as well, and at a later stage of cancer discovery. In the ERSPC trial, higher-grade cancer (Gleason score ≥7) was more common in the control group (45.2%) versus the screened group (27.8%), with a 40% greater incidence of locally advanced and metastatic cancer (4). Undeniably, victims of advanced prostate cancer endure more invasive and harmful procedures than those with organ-confined disease. Second, the Task Force analysis focused on mortality and ignored the substantial illness associated with living with advanced cancer. Disseminated prostate cancer is characterized by painful bone metastases, pathologic fractures, and urinary tract obstruction. A comprehensive comparative analysis of benefits and harms in screened and control populations should consider the complications of advanced cancer, which could be more common in unscreened groups. Third, we believe that the Task Force recommendation lacks adequate consideration of high-risk populations, including men with a family history of prostate cancer and men of African descent, who have a 1.4-times higher risk for being diagnosed with and 2- to 3-times higher risk for dying of prostate cancer compared with European American men (10). Fourth, the USPSTF did not adequately emphasize epidemiologic data that show that since the widespread use of PSA testing began in the early 1990s, there has been a 40% decrease in prostate cancer deaths and a 75% decrease in presentation with advanced disease at initial diagnosis, which is attributed, in large part, to PSA screening (11). A recent National Institutes of Health Consensus Development Conference concluded that “prior to the adoption of PSA screening, the majority of prostate cancer was detected because of symptoms of advanced cancer or a nodule found on digital rectal examination. The symptomatic tumors were usually high-grade, advanced, and often lethal” (12).
Finally, the Task Force recommendation opposes PSA testing regardless of age. The expected life span for a man aged 75 years is approximately 10 years but reaches 30 years for men at age 45 to 50 years. It is plausible that many men aged 75 years or older will die of other causes before developing metastatic prostate cancer, but the current recommendation, arguably to avoid adverse effects of screening, could result in delayed diagnosis of curable cancer in young men who may then present with advanced disease and illness and ultimately die of prostate cancer. The Task Force recommendation relies solely on mortality data from the PLCO and the ERSPC and early data from the Prostate Cancer Intervention Versus Observation Trial (1). We believe that studies with only a 10-year median follow-up are insufficient to dictate how 50- to 60-year-old men with prostate cancer should be treated.
The recommendations of the USPSTF carry considerable weight with Medicare and other third-party insurers and could affect the health and lives of men at high risk for life-threatening disease. We believe that eliminating reimbursement for PSA testing would take us back to an era when prostate cancer was often discovered at advanced and incurable stages. At this point, we suggest that physicians review the evidence, follow the continuing dialogue closely, and individualize prostate cancer screening decisions on the basis of informed patient preferences.
This article was published at www.annals.org on 22 May 2012.
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Tanner J., Caverly, MD, Instructor of Medicine
University of Colorado Denver School of Medicine
May 24, 2012
NUMBERS NEEDED - BUT NOT RELATIVE RISK
Weighing the potential benefits and harms of PSA-screening is difficult. In their response to the updated guidelines, Catalona et al. claim that the USPSTF underestimated the benefits of PSA-screening. This claim would have been more credible had they not presented the benefit data exclusively in terms of relative risk reduction - a format that has long been known to inflate estimations of benefit (1). Catalona and colleagues also claim that the USPSTF overestimated the harms of PSA- screening. Unfortunately, their response did not attempt to quantify the harms of overdiagnosis and overtreatment at all, reinforcing a view that these downsides can simply be ignored. Interpretation of existing evidence and which evidence to highlight continues to differ dramatically in the PSA-screening debate. When attempting to think clearly about this issue, however, there is no substitute for directly comparing quantitative estimates of both benefits and harms in the best format available. In this case, the best format would be numbers needed to screen, numbers needed to treat, and numbers needed to harm - not relative risk.
1. Fahey, T., S. Griffiths, and T. J. Peters. "Evidence Based Purchasing: Understanding Results of Clinical Trials and Systematic Reviews." BMJ?: British Medical Journal 311, no. 7012 (October 21, 1995): 1056-1060.
Brandon P, Combs, Assistant Professor of Medicine
University of Colorado School of Medicine
Resistance to Change Practice
The recent editorial by Catalona, et al in response to updated PSA screening guidelines by the USPSTF is emblematic of the systemic problem of overuse and resistance to incorporate high quality evidence from randomized controlled trials into clinical practice (1). It is impressive that the USPSTF should be criticized for relying on the two largest published randomized controlled trials to date and focusing on the balance between mortality benefit and harms of treatment instead of theoretical downstream harms of undiagnosed malignancy. It is also misleading to suggest that the mortality benefit observed with radical prostatectomy versus watchful waiting in the Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4), where only 5% of prostate tumors were identified by screening and 75% were palpable at presentation, offers evidence in support of screening for cancer by PSA (2). Finally, though use of relative risk reduction as opposed to absolute risk reduction in expressing benefit of a treatment is a persuasive means to sell devices or drugs, it does not contribute meaningfully to clinical discourse between patient and physician when weighing the risks and benefits of screening for cancer.
1. Catalona WJ, D'Amico AV, Fitzgibbons WF, Kosoko-Lasaki O, Leslie SW, Lynch HT, Moul JW, Rendell MS, Walsh PC. "What the U.S. Preventive Services Task Force Missed in Its Prostate Cancer Screening Recommendation." Ann Intern Med. 2012 [Epub ahead of print 22 May 2012].
2. Bill-Axelson A, Holmberg L, Ruutu M, Garmo H, Stark JR, Busch C, et al; SPCG-4 Investigators. Radical prostatectomy versus watchful waiting in early prostate cancer. N Engl J Med. 2011;364:1708-17.
Radhakanth K, Shenoy, Radiation Oncologist
Queen Elizabeth Hospital
May 26, 2012
Re:Resistance to Change Practice
1Mary Pat Raimondi, MS, RD, 2Robert Ratner, MD, 3Todd Hobbs, MD, 4Henry Rodriguez, MD
1Vice President of Strategic Policy and Partnerships, Academy of Nutrition and Dietetics, Washington, DC 2Chief Scientific & Medical Officer, American Diabetes Association, Alexandria, VA 3Chief
November 20, 2015
Conflict of Interest:
MPR, RR, and HR have no disclosures; TH is an employee of Novo Nordisk, Inc.
Comment on: Screening for Abnormal Blood Glucose and Type 2 Diabetes Mellitus: U.S. Preventive Services Task Force Recommendation Statement
To the Editor:The final U.S. Preventive Services Task Force (USPSTF) diabetes screening guideline, published on October 26, 2015, (1) improves upon the 2008 guideline it replaces, as more of the 8.1 million Americans living with undiagnosed diabetes and the 86 million with prediabetes (2) are targeted for screening. Also, this “B” level guideline recommends intensive lifestyle change programs for adults identified with abnormal blood glucose, a tremendous step forward in helping people with prediabetes prevent progression to type 2 diabetes and those with diabetes prevent complications. That’s the good news.Unfortunately, the final guideline will fail to identify significant numbers of Americans with undiagnosed diabetes or prediabetes – and denies them important benefits of preventive interventions or early disease detection and treatment. That’s a significant step backwards.Compared with the 2014 draft, the final guideline changed the population targeted for screening from all adults with widely accepted risk factors for diabetes to a narrower population of adults aged 40 to 70 years who are overweight or obese. (1) Absent are several critical factors placing patients at high risk for diabetes. Rates of undiagnosed diabetes are significantly higher in Asian Americans (61%+), Hispanic Americans (50%+), and Black Americans (33%+) compared with non-Hispanic whites. (3) The focus on weight alone is particularly problematic for Asian Americans, who are at risk for diabetes at a lower body mass index than USPSTF identifies for screening. (4)Additionally, women with a history of gestational diabetes are at the highest risk, with 50% developing type 2 diabetes within five years. (5) For many new mothers with GDM, beginning screening at age 40 is too little, too late.Most fundamentally, the final guideline portrays diabetes solely as a risk factor for cardiovascular disease, (1) completely ignoring the importance of screening to detect type 2 diabetes and treat it appropriately in order to reduce retinopathy, nephropathy and neuropathy – the complications most amenable to prevention through glucose control.Despite these shortcomings, the new guideline will encourage screening at no cost for many more at-risk patients, as well as expand access to intensive behavioral counseling for those with abnormal glucose levels. Moving forward, we encourage primary care providers to review all risk factors identified by the American Diabetes Association in considering patients for screening. Our organizations stand ready to support the primary care community in its efforts to tackle the enormous and growing challenges posed by diabetes. Our patients deserve nothing less.1. Siu A, on behalf of the U.S. Preventive Services Task Force. Screening for abnormal blood glucose and type 2 diabetes mellitus: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2015; doi:10.7326/M15-2345.2. Division of Diabetes Translation, National Center for Chronic Disease Prevention and Health Promotion. National Diabetes Statistics Report, 2014. Atlanta: Centers for Disease Control and Prevention; 2014. Accessed at www.cdc.gov/diabetes/pubs/statsreport14 /national-diabetes-report-web.pdf on 16 November 2015.3. Menke A, Casagrande S, Geiss L, Cowie C. Prevalence of and trends in diabetes among adults in the United States, 1988-2012. JAMA. 2015; 314(10):1021-1029.4. Hsu WC, Araneta MR, Kanaya AM, Chiang JL, Fujimoto W. BMI cut points to identify at-risk Asian Americans for type 2 diabetes screening. Diabetes Care. 2015; 38:150–158. 5. Kim C, Newton K, Knopp R. Gestational diabetes and the incidence of type 2 diabetes. Diabetes Care. 2002; 25(10):1862-1868.
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