Prostate cancer screening with prostate-specific antigen (PSA) test: A systematic review and meta-analysis

Dragan Ilic, Mia Djulbegovic, Jaehung Jung, Eu Chang Hwang, Qi Zhou, Anne Cleves, Thomas Agoritsas, Philipp Dahm

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article numberk3519
JournalBMJ (Online)
Volume362
DOIs
Publication statusPublished - 2018 Jan 1

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Prostate-Specific Antigen
Early Detection of Cancer
Meta-Analysis
Prostatic Neoplasms
Mortality
Incidence
Biopsy
Prostate
Randomized Controlled Trials
Whole Body Imaging
Information Storage and Retrieval
Urinary Incontinence
Erectile Dysfunction
Sepsis
Guidelines
Safety
Therapeutics

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

Ilic, Dragan ; Djulbegovic, Mia ; Jung, Jaehung ; Hwang, Eu Chang ; Zhou, Qi ; Cleves, Anne ; Agoritsas, Thomas ; Dahm, Philipp. / Prostate cancer screening with prostate-specific antigen (PSA) test : A systematic review and meta-analysis. In: BMJ (Online). 2018 ; Vol. 362.
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abstract = "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.",
author = "Dragan Ilic and Mia Djulbegovic and Jaehung Jung and Hwang, {Eu Chang} and Qi Zhou and Anne Cleves and Thomas Agoritsas and Philipp Dahm",
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Ilic, D, Djulbegovic, M, Jung, J, Hwang, EC, Zhou, Q, Cleves, A, Agoritsas, T & Dahm, P 2018, 'Prostate cancer screening with prostate-specific antigen (PSA) test: A systematic review and meta-analysis', BMJ (Online), vol. 362, k3519. https://doi.org/10.1136/bmj.k3519

Prostate cancer screening with prostate-specific antigen (PSA) test : A systematic review and meta-analysis. / Ilic, Dragan; Djulbegovic, Mia; Jung, Jaehung; Hwang, Eu Chang; Zhou, Qi; Cleves, Anne; Agoritsas, Thomas; Dahm, Philipp.

In: BMJ (Online), Vol. 362, k3519, 01.01.2018.

Research output: Contribution to journalArticle

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T1 - Prostate cancer screening with prostate-specific antigen (PSA) test

T2 - A systematic review and meta-analysis

AU - Ilic, Dragan

AU - Djulbegovic, Mia

AU - Jung, Jaehung

AU - Hwang, Eu Chang

AU - Zhou, Qi

AU - Cleves, Anne

AU - Agoritsas, Thomas

AU - Dahm, Philipp

PY - 2018/1/1

Y1 - 2018/1/1

N2 - 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.

AB - 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.

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