School of Public Health and Preventive Medicine, Monash University, Victoria, Australia.
National Clinicians Scholars Program, Yale University School of Medicine, and Veterans Affairs Connecticut Healthcare System, New Haven, Connecticut, USA.
BMJ. 2018 Sep 5;362:k3519. doi: 10.1136/bmj.k3519.
To investigate the efficacy and safety of prostate-specific antigen (PSA) testing to screen for prostate cancer.
Systematic review and meta-analysis.
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.
Randomised controlled trials comparing PSA screening with usual care in men without a diagnosis of prostate cancer.
At least two reviewers screened studies, extracted data, and assessed the quality of eligible studies. A parallel guideline committee 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.
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.
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.
PROSPERO registration number CRD42016042347.
研究前列腺特异性抗原（PSA）检测筛查前列腺癌的疗效和安全性。
系统评价和荟萃分析。
Cochrane 对照试验中心注册库、Web of Science、Embase、Scopus、OpenGrey、LILACS 和 Medline 的电子检索，以及 2018 年 4 月之前的科学会议摘要和试验登记处的检索。
比较 PSA 筛查与无前列腺癌诊断男性常规护理的随机对照试验。
至少两名评审员筛选研究、提取数据并评估合格研究的质量。一个平行的指导委员会（快速推荐）就系统评价的设计和解释提供了意见，包括对患者重要的结局的选择。我们使用随机效应模型获得合并发病率比值（IRR），并在可行的情况下，根据年龄、筛查频率、家族史、种族和社会经济水平进行预先定义的亚组分析，以及基于偏倚风险的敏感性分析。证据质量采用 GRADE 方法评估。
纳入了 5 项随机对照试验，共纳入 721718 名男性。研究在筛查频率和间隔、活检 PSA 阈值以及偏倚风险方面存在差异。考虑到整个证据体，筛查可能对全因死亡率没有影响（IRR 0.99，95%CI 0.98 至 1.01；中等确定性），也可能对前列腺特异性死亡率没有影响（IRR 0.96，0.85 至 1.08；低确定性）。风险较低的研究（n=1）的敏感性分析也表明，筛查似乎对全因死亡率没有影响（IRR 1.0，0.98 至 1.02；中等确定性），但可能对前列腺特异性死亡率有较小的影响（IRR 0.79，0.69 至 0.91；中等确定性）。这相当于每筛查 1000 名男性，10 年内可减少 1 例前列腺癌死亡。纳入试验中关于活检和治疗相关并发症的直接比较数据有限。使用建模，我们估计每筛查 1000 名男性，将分别有 1、3 和 25 名男性因败血症住院、需要尿失禁垫和报告勃起功能障碍。
最佳情况下，前列腺癌筛查在 10 年内可使疾病特异性死亡率略有降低，但不会影响总体死亡率。考虑基于 PSA 的筛查的临床医生和患者需要权衡这些益处与筛查的潜在短期和长期危害，包括活检和随后治疗的并发症，以及过度诊断和过度治疗的风险。
PROSPERO 注册号 CRD42016042347。
