title: Counterpoint: Randomized trials provide the strongest evidence for clinical guidelines: The US Preventive Services Task Force and Prostate Cancer Screening.
abstract: BACKGROUND
  The US Preventive Services Task Force recommended against prostate-specific antigen (PSA) screening for prostate cancer based primarily on 2 large long-term randomized-controlled trials (RCTs) and a systematic review of harms resulting from screening.
  
  
  OBJECTIVE
  To support use of large, long-term randomized trials as the evidence base for clinical guidelines on screening and to draw attention to limitations of modeling studies used for this purpose.
  
  
  METHODS
  We respond to critiques of use of RCTs as the primary evidence base, considering the results of the Prostate, Lung, Colorectal and Ovarian (PLCO) and European Randomized Study of Screening for Prostate Cancer (ERSPC) trials, documented harms resulting from PSA screening, and methodological concerns with modeling studies.
  
  
  RESULTS
  The PLCO and ERSPC provided 11-13 years of follow-up on over 250,000 subjects. The PLCO, despite limitations, is most representative of US populations, screening and treatment practices, and showed no mortality benefit resulting from annual PSA testing after 13 years of follow-up. The confidence interval was narrow and precluded more than a 13% relative mortality reduction. Competing causes of mortality in older men make it progressively less likely that longer follow-up will demonstrate a large absolute reduction in disease-specific mortality. With continued screening, the increasing prevalence of asymptomatic cancers in older men will increase the rate of overdiagnosis. Potential harms from screening and treatment are significant.
  
  
  CONCLUSIONS
  Projections from models are subject to mistaken assumptions and investigator biases, and should not be accorded the same weight as evidence from RCTs. Current empiric evidence is sufficient to support the US Preventive Services Task Force guideline that clinicians should recommend against PSA screening for prostate cancer.
authors.affiliation: Department of Family and Community Medicine, Center for Healthcare Policy and Research, University of California, Davis, Sacramento, CA 95817, USA. jamelnikow@ucdavis.edu
authors.forename: Joy
authors.initials: J
authors.lastname: Melnikow
authors.forename: Michael
authors.initials: M
authors.lastname: LeFevre
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Wilt
authors.forename: Virginia A
authors.initials: VA
authors.lastname: Moyer
mesh_terms: D055088:Early Detection of Cancer / Q000592:standards*; D019317:Evidence-Based Medicine / Q000379:methods*; D006291:Health Policy; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000517:prevention & control*