What the U.S. Preventive Services Task Force Missed in Its Prostate Cancer Screening Recommendation

Abstract

In the Balance17 July 2012What the U.S. Preventive Services Task Force Missed in Its Prostate Cancer Screening RecommendationFREEWilliam 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, and Patrick C. Walsh, MDWilliam J. Catalona, MDFrom Northwestern University Feinberg School of Medicine, Chicago, Illinois; Brigham and Women's Hospital and Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts; Creighton University School of Medicine, Omaha, Nebraska; Duke Cancer Institute and Duke University School of Medicine, Durham, North Carolina; and James Buchanan Brady Urologic Institute, Johns Hopkins Medical Institutions, Baltimore, Maryland., Anthony V. D'Amico, MDFrom Northwestern University Feinberg School of Medicine, Chicago, Illinois; Brigham and Women's Hospital and Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts; Creighton University School of Medicine, Omaha, Nebraska; Duke Cancer Institute and Duke University School of Medicine, Durham, North Carolina; and James Buchanan Brady Urologic Institute, Johns Hopkins Medical Institutions, Baltimore, Maryland., William F. Fitzgibbons, MDFrom Northwestern University Feinberg School of Medicine, Chicago, Illinois; Brigham and Women's Hospital and Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts; Creighton University School of Medicine, Omaha, Nebraska; Duke Cancer Institute and Duke University School of Medicine, Durham, North Carolina; and James Buchanan Brady Urologic Institute, Johns Hopkins Medical Institutions, Baltimore, Maryland., Omofolasade Kosoko-Lasaki, MDFrom Northwestern University Feinberg School of Medicine, Chicago, Illinois; Brigham and Women's Hospital and Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts; Creighton University School of Medicine, Omaha, Nebraska; Duke Cancer Institute and Duke University School of Medicine, Durham, North Carolina; and James Buchanan Brady Urologic Institute, Johns Hopkins Medical Institutions, Baltimore, Maryland., Stephen W. Leslie, MDFrom Northwestern University Feinberg School of Medicine, Chicago, Illinois; Brigham and Women's Hospital and Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts; Creighton University School of Medicine, Omaha, Nebraska; Duke Cancer Institute and Duke University School of Medicine, Durham, North Carolina; and James Buchanan Brady Urologic Institute, Johns Hopkins Medical Institutions, Baltimore, Maryland., Henry T. Lynch, MDFrom Northwestern University Feinberg School of Medicine, Chicago, Illinois; Brigham and Women's Hospital and Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts; Creighton University School of Medicine, Omaha, Nebraska; Duke Cancer Institute and Duke University School of Medicine, Durham, North Carolina; and James Buchanan Brady Urologic Institute, Johns Hopkins Medical Institutions, Baltimore, Maryland., Judd W. Moul, MDFrom Northwestern University Feinberg School of Medicine, Chicago, Illinois; Brigham and Women's Hospital and Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts; Creighton University School of Medicine, Omaha, Nebraska; Duke Cancer Institute and Duke University School of Medicine, Durham, North Carolina; and James Buchanan Brady Urologic Institute, Johns Hopkins Medical Institutions, Baltimore, Maryland., Marc S. Rendell, MDFrom Northwestern University Feinberg School of Medicine, Chicago, Illinois; Brigham and Women's Hospital and Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts; Creighton University School of Medicine, Omaha, Nebraska; Duke Cancer Institute and Duke University School of Medicine, Durham, North Carolina; and James Buchanan Brady Urologic Institute, Johns Hopkins Medical Institutions, Baltimore, Maryland., and Patrick C. Walsh, MDFrom Northwestern University Feinberg School of Medicine, Chicago, Illinois; Brigham and Women's Hospital and Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts; Creighton University School of Medicine, Omaha, Nebraska; Duke Cancer Institute and Duke University School of Medicine, Durham, North Carolina; and James Buchanan Brady Urologic Institute, Johns Hopkins Medical Institutions, Baltimore, Maryland.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-157-2-201207170-00463 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail 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.References1. Moyer VA; U.S. Preventive Services Task Force. Screening for prostate cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2012;157:120-34. LinkGoogle Scholar2. Chou R, Croswell JM, Dana T, Bougatsos C, Blazina I, Fu R, et al. Screening for prostate cancer: a review of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med. 2011;155:762-71. [PMID: 21984740] LinkGoogle Scholar3. Andriole GL, Crawford ED, Grubb RL, Buys SS, Chia D, Church TR, et al; PLCO Project Team. Prostate cancer screening in the randomized Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial: mortality results after 13 years of follow-up. J Natl Cancer Inst. 2012;104:125-32. [PMID: 22228146] CrossrefMedlineGoogle Scholar4. Schröder FH, Hugosson J, Roobol MJ, Tammela TL, Ciatto S, Nelen V, et al; ERSPC Investigators. Screening and prostate-cancer mortality in a randomized European study. N Engl J Med. 2009;360:1320-8. [PMID: 19297566] CrossrefMedlineGoogle Scholar5. Schröder FH, Hugosson J, Roobol MJ, Tammela TL, Ciatto S, Nelen V, et al; ERSPC Investigators. Prostate-cancer mortality at 11 years of follow-up. N Engl J Med. 2012;366:981-90. [PMID: 22417251] CrossrefMedlineGoogle Scholar6. 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. [PMID: 21542742] CrossrefMedlineGoogle Scholar7. Pinsky PF, Blacka A, Kramer BS, Miller A, Prorok PC, Berg C. Assessing contamination and compliance in the prostate component of the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Clin Trials. 2010;7:303-11. [PMID: 20571134] CrossrefMedlineGoogle Scholar8. Roobol MJ, Kerkhof M, Schröder FH, Cuzick J, Sasieni P, Hakama M, et al. Prostate cancer mortality reduction by prostate-specific antigen-based screening adjusted for nonattendance and contamination in the European Randomised Study of Screening for Prostate Cancer (ERSPC). Eur Urol. 2009;56:584-91. [PMID: 19660851] CrossrefMedlineGoogle Scholar9. Hugosson J, Carlsson S, Aus G, Bergdahl S, Khatami A, Lodding P, et al. Mortality results from the Göteborg randomised population-based prostate-cancer screening trial. Lancet Oncol. 2010;11:725-32. [PMID: 20598634] CrossrefMedlineGoogle Scholar10. Chornokur G, Dalton K, Borysova ME, Kumar NB. Disparities at presentation, diagnosis, treatment, and survival in African American men, affected by prostate cancer. Prostate. 2011;71:985-97. [PMID: 21541975] CrossrefMedlineGoogle Scholar11. Etzioni R, Tsodikov A, Mariotto A, Szabo A, Falcon S, Wegelin J, et al. Quantifying the role of PSA screening in the US prostate cancer mortality decline. Cancer Causes Control. 2008;19:175-81. [PMID: 18027095] CrossrefMedlineGoogle Scholar12. Ganz PA, Barry JM, Burke W, Col NF, Corso PS, Dodson E, et al. National Institutes of Health State-of-the-Science Conference: Role of Active Surveillance in the Management of Men With Localized Prostate Cancer. Ann Intern Med. 2012;156:591-595. [PMID: 22351514] LinkGoogle Scholar Comments0 CommentsSign In to Submit A Comment 1Mary Pat Raimondi, MS, RD, 2Robert Ratner, MD, 3Todd Hobbs, MD, 4Henry Rodriguez, MD1Vice President of Strategic Policy and Partnerships, Academy of Nutrition and Dietetics, Washington, DC 2Chief Scientific & Medical Officer, American Diabetes Association, Alexandria, VA 3Chief 23 November 2015 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. Disclosures: MPR, RR, and HR have no disclosures; TH is an employee of Novo Nordisk, Inc. Radhakanth K, Shenoy, Radiation OncologistQueen Elizabeth Hospital29 May 2012 Re:Resistance to Change Practice I have seen the comments for and against the screening. W Catalona et al state that USPSTF can not dictate how men between 50 and 60 years should be treated.USPSTF does not in fact dictate how these men should be treated. It simply advises against screening, excluding men who have been already treated for prostate cancer.This does not equate in any way with dictating how to treat. You can treat what you have diagnosed.USPSTF does not tell the physicians how to treat. The article is very clear on the recommendation of USPSTF. A caveat perhaps would be high risk young population as we see in the Afro Caribbean population. Conflict of Interest:None declared Brandon P, Combs, Assistant Professor of MedicineUniversity of Colorado School of Medicine25 May 2012 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, evidence in support of screening for cancer by PSA (2). use of risk reduction as to risk reduction in benefit of a treatment is a to or it does not to clinical between patient and when the and benefits of screening for Catalona MS, the U.S. Preventive Services Task Force Missed in Its Prostate Cancer Screening Ann Intern Med. 2012 of May 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. of Interest:None declared MD, of MedicineUniversity of Colorado School of May 2012 the potential benefits and harms of is In response to the updated Catalona et al. claim that the USPSTF underestimated the benefits of claim would have been more had not the benefit data in of risk reduction a that has been to of benefit (1). Catalona and also claim that the USPSTF overestimated the harms of screening. response did not to the harms of and at a view that these can simply be of evidence and which evidence to to differ in the to this there is no for of both benefits and harms in the In this the would be numbers to numbers to and numbers to harm not S. and T. J. of and Medical of Interest:None declared Article, and Disclosure Northwestern University Feinberg School of Medicine, Chicago, Illinois; Brigham and Women's Hospital and Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts; Creighton University School of Medicine, Omaha, Nebraska; Duke Cancer Institute and Duke University School of Medicine, Durham, North Carolina; and James Buchanan Brady Urologic Institute, Johns Hopkins Medical Institutions, Baltimore, can be at Marc S. Rendell, MD, The Creighton Diabetes North Omaha, North Chicago, Brigham and Women's 75 Boston, Medical North Health of and Creighton Omaha, of Division of North Omaha, Cancer Center and of Preventive Medicine, Creighton Omaha, Division of Urologic Duke Duke University Medical Durham, The Creighton Diabetes North Omaha, Johns Hopkins Baltimore, and Catalona, Fitzgibbons, Moul, Rendell, and of the Catalona, D'Amico, Leslie, Lynch, Rendell, of the Catalona, D'Amico, Leslie, Moul, Rendell, of the article for important Catalona, D'Amico, Fitzgibbons, Leslie, Moul, Rendell, of the Catalona, D'Amico, Fitzgibbons, Kosoko-Lasaki, Leslie, Lynch, Moul, Rendell, or Leslie, and of Catalona, D'Amico, article was published at on May for Prostate U.S. Preventive Services Task Force Recommendation Statement Moyer and Prostate Cancer We and W. prostate cancer could be an screening of prostate cancer of Cancer Cancer prostate cancer screening in the a for and prostate cancer treatment The role of and risk of antigen in and of and PSA in the of Prostate in Screening and Men With a of Prostate effect of the USPSTF PSA screening recommendation on prostate cancer incidence in the of recommendations against prostate cancer screening with prostate for and prostate in prostate cancer risk a Screening for Prostate Cancer and of Prostate Cancer as for Prostate of prostate cancer a Cancer Screening and the cancer screening and treatment in an era of Cancer Screening American and The Health and of the U.S. Preventive Services Task Force against Prostate Screening on Prostate and Cancer prostate cancer and radical prostatectomy in the and of the Association and Prostate of the American Association early detection of prostate cancer will we cancer incidence and mortality in the of the European Randomized Study of Screening For Prostate Cancer of radiation and urologists on recommendations of prostate-specific antigen screening for prostate for Prostate in the clinical and of the the potential use of in for prostate cancer to in the for Screening for to identifies and for prostate the Men to be in and of Prostate of Screening and Prostate Cancer in high risk disease and In To on the of and Cancer and for prostate cancer: an updated and Screening for Prostate U.S. Preventive Services Task Force Recommendation to for Prostate Cancer July July 2012 July 2012 & 2012 by American of