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Original Investigation
March 6, 2018

Effect of a Low-Intensity PSA-Based Screening Intervention on Prostate Cancer MortalityThe CAP Randomized Clinical Trial

Author Affiliations
  • 1Department of Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, England
  • 2National Institute for Health Research Bristol Biomedical Research Centre, University Hospitals Bristol NHS Foundation Trust and University of Bristol, Bristol, England
  • 3National Institute for Health Research Collaboration for Leadership in Applied Health Research and Care West, University Hospitals Bristol NHS Trust, Bristol, England
  • 4Bristol Randomised Trials Collaboration, University of Bristol, Bristol, England
  • 5Department of Health Sciences, University of York and Hull York Medical School, York, England
  • 6Urology Department, Royal United Hospital, Bath, England
  • 7Nuffield Department of Surgical Sciences, University of Oxford, Oxford, England
  • 8Bristol, North Somerset, and South Gloucestershire Clinical Commissioning Group, Bristol, England
  • 9Department of Oncology, Addenbrooke’s Hospital, University of Cambridge, Cambridge, England
  • 10Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, England
JAMA. 2018;319(9):883-895. doi:10.1001/jama.2018.0154
Key Points

Question  What is the effect of an invitation to a single prostate-specific antigen (PSA) screening on prostate cancer detection and median 10-year prostate cancer mortality?

Findings  In this randomized clinical trial comparing men aged 50 to 69 years undergoing a single PSA screening (n = 189 386) vs controls not undergoing a PSA screening (n = 219 439), the proportion of men diagnosed with prostate cancer was higher in the intervention group (4.3%) than in the control group (3.6%); however, there was no significant difference in prostate cancer mortality (0.30 per 1000 person-years for the intervention group vs 0.31 for the control group) after a median follow-up of 10 years.

Meaning  The single PSA screening intervention detected more prostate cancer cases but had no significant effect on prostate cancer mortality after a median follow-up of 10 years.

Abstract

Importance  Prostate cancer screening remains controversial because potential mortality or quality-of-life benefits may be outweighed by harms from overdetection and overtreatment.

Objective  To evaluate the effect of a single prostate-specific antigen (PSA) screening intervention and standardized diagnostic pathway on prostate cancer–specific mortality.

Design, Setting, and Participants  The Cluster Randomized Trial of PSA Testing for Prostate Cancer (CAP) included 419 582 men aged 50 to 69 years and was conducted at 573 primary care practices across the United Kingdom. Randomization and recruitment of the practices occurred between 2001 and 2009; patient follow-up ended on March 31, 2016.

Intervention  An invitation to attend a PSA testing clinic and receive a single PSA test vs standard (unscreened) practice.

Main Outcomes and Measures  Primary outcome: prostate cancer–specific mortality at a median follow-up of 10 years. Prespecified secondary outcomes: diagnostic cancer stage and Gleason grade (range, 2-10; higher scores indicate a poorer prognosis) of prostate cancers identified, all-cause mortality, and an instrumental variable analysis estimating the causal effect of attending the PSA screening clinic.

Results  Among 415 357 randomized men (mean [SD] age, 59.0 [5.6] years), 189 386 in the intervention group and 219 439 in the control group were included in the analysis (n = 408 825; 98%). In the intervention group, 75 707 (40%) attended the PSA testing clinic and 67 313 (36%) underwent PSA testing. Of 64 436 with a valid PSA test result, 6857 (11%) had a PSA level between 3 ng/mL and 19.9 ng/mL, of whom 5850 (85%) had a prostate biopsy. After a median follow-up of 10 years, 549 (0.30 per 1000 person-years) died of prostate cancer in the intervention group vs 647 (0.31 per 1000 person-years) in the control group (rate difference, −0.013 per 1000 person-years [95% CI, −0.047 to 0.022]; rate ratio [RR], 0.96 [95% CI, 0.85 to 1.08]; P = .50). The number diagnosed with prostate cancer was higher in the intervention group (n = 8054; 4.3%) than in the control group (n = 7853; 3.6%) (RR, 1.19 [95% CI, 1.14 to 1.25]; P < .001). More prostate cancer tumors with a Gleason grade of 6 or lower were identified in the intervention group (n = 3263/189 386 [1.7%]) than in the control group (n = 2440/219 439 [1.1%]) (difference per 1000 men, 6.11 [95% CI, 5.38 to 6.84]; P < .001). In the analysis of all-cause mortality, there were 25 459 deaths in the intervention group vs 28 306 deaths in the control group (RR, 0.99 [95% CI, 0.94 to 1.03]; P = .49). In the instrumental variable analysis for prostate cancer mortality, the adherence-adjusted causal RR was 0.93 (95% CI, 0.67 to 1.29; P = .66).

Conclusions and Relevance  Among practices randomized to a single PSA screening intervention vs standard practice without screening, there was no significant difference in prostate cancer mortality after a median follow-up of 10 years but the detection of low-risk prostate cancer cases increased. Although longer-term follow-up is under way, the findings do not support single PSA testing for population-based screening.

Trial Registration  ISRCTN Identifier: ISRCTN92187251

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