Prostate cancer screening with prostate-specific antigen (PSA) test: a systematic review and meta-analysisBMJ 2018; 362 doi: https://doi.org/10.1136/bmj.k3519 (Published 05 September 2018) Cite this as: BMJ 2018;362:k3519
- Dragan Ilic, professor1,
- Mia Djulbegovic, postdoctoral fellow2,
- Jae Hung Jung, associate professor3,
- Eu Chang Hwang, associate professor4 5,
- Qi Zhou, statistician6,
- Anne Cleves, medical librarian7,
- Thomas Agoritsas, assistant professor6 8,
- Philipp Dahm, professor5
- 1School of Public Health and Preventive Medicine, Monash University, Victoria, Australia
- 2National Clinicians Scholars Program, Yale University School of Medicine, and Veterans Affairs Connecticut Healthcare System, New Haven, Connecticut, USA
- 3Department of Urology, Yonsei University Wonju College of Medicine, Wonju, Korea
- 4Department of Urology, Chonnam National University Medical School, Gwangju, Korea
- 5Urology Section, Minneapolis VAMC and Department of Urology, University of Minnesota, Minneapolis, Minnesota, USA
- 6Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada
- 7Velindre NHS Trust, Cardiff University Library Services, Velindre Cancer Centre, Cardiff, Wales
- 8Division of General Internal Medicine and Division of Epidemiology, Department of Internal medicine, Rehabilitation and Geriatrics, University Hospitals of Geneva, Geneva, Switzerland
- Corresponding to: P Dahm
- Accepted 31 July 2018
Objective To investigate the efficacy and safety of prostate-specific antigen (PSA) testing to screen for prostate cancer.
Design Systematic review and meta-analysis.
Data sources Electronic search of Cochrane Central Register of Controlled Trials, Web of Science, Embase, Scopus, OpenGrey, LILACS, and Medline, and search of scientific meeting abstracts and trial registers to April 2018.
Eligibility criteria for selecting studies Randomised controlled trials comparing PSA screening with usual care in men without a diagnosis of prostate cancer.
Data extraction At least two reviewers screened studies, extracted data, and assessed the quality of eligible studies. A parallel guideline committee (BMJ Rapid Recommendation) provided input on the design and interpretation of the systematic review, including selection of outcomes important to patients. We used a random effects model to obtain pooled incidence rate ratios (IRR) and, when feasible, conducted subgroup analyses (defined a priori) based on age, frequency of screening, family history, ethnicity, and socioeconomic level, as well as a sensitivity analysis based on the risk of bias. The quality of the evidence was assessed with the GRADE approach.
Results Five randomised controlled trials, enrolling 721 718 men, were included. Studies varied with respect to screening frequency and intervals, PSA thresholds for biopsy, and risk of bias. When considering the whole body of evidence, screening probably has no effect on all-cause mortality (IRR 0.99, 95% CI 0.98 to 1.01; moderate certainty) and may have no effect on prostate-specific mortality (IRR 0.96, 0.85 to 1.08; low certainty). Sensitivity analysis of studies at lower risk of bias (n=1) also demonstrates that screening seems to have no effect on all-cause mortality (IRR 1.0, 0.98 to 1.02; moderate certainty) but may have a small effect on prostate-specific mortality (IRR 0.79, 0.69 to 0.91; moderate certainty). This corresponds to one less death from prostate cancer per 1000 men screened over 10 years. Direct comparative data on biopsy and treatment related complications from the included trials were limited. Using modelling, we estimated that for every 1000 men screened, approximately 1, 3, and 25 more men would be hospitalised for sepsis, require pads for urinary incontinence, and report erectile dysfunction, respectively.
Conclusions At best, screening for prostate cancer leads to a small reduction in disease-specific mortality over 10 years but has does not affect overall mortality. Clinicians and patients considering PSA based screening need to weigh these benefits against the potential short and long term harms of screening, including complications from biopsies and subsequent treatment, as well as the risk of overdiagnosis and overtreatment.
Systematic review registration PROSPERO registration number CRD42016042347.
Contributors: DI, MD, and PD were involved in the conception and design of the review. DI, MD, AC, and PD developed the search strategy and performed study selection. DI, MD, JHJ, ECH, and PD extracted data from included studies. QZ, TA, and PD were involved in the data analysis. DI, MD, JHJ, ECH, QZ, TA, and PD were involved in the interpretation and discussion of results. All authors drafted the manuscript, contributed to the drafting of the review, and revised it critically for important intellectual content. All authors approved the final version of the article. All authors had access to all of the data in the study and can take responsibility for the integrity of the data and the accuracy of the data analysis. PD is guarantor.
Funding: This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
Competing interests All authors have completed the Unified Competing Interest form (available on request from the corresponding author) and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.
Ethical approval: Not required.
Data sharing: No additional data available.
Transparency: DI and PD affirm that the manuscript is an honest, accurate, and transparent account of the study being reported; no important aspects of the study have been omitted.
Patient involvement: As further described in the Methods section, three patient representatives helped inform the questions, outcomes and thresholds of clinical importance for this systematic review.
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