Faculty of Social Sciences, University of Tampere, Arvo B335, Box 100, 33014, Tampere, Finland.
Department of Urology, Faculty of Medicine, Helsinki University Hospital, University of Helsinki, Helsinki, Finland.
Eur J Epidemiol. 2017 Jun;32(6):521-527. doi: 10.1007/s10654-017-0292-5. Epub 2017 Jul 31.
The current evidence of PSA-based prostate cancer screening shows a reduction in cause-specific mortality, but with substantial overdiagnosis. Recently, new developments in detection of clinically relevant prostate cancer include multiple kallikreins as biomarkers besides PSA, and multiparametric magnetic resonance imaging (mpMRI) for biopsy decision. They offer opportunities for improving the outcomes in screening, particularly reduction in overdiagnosis and higher specificity for potentially lethal cancer. A population-based randomized screening trial will be started, with 67,000 men aged 55-67 years at entry. A quarter of the men will be allocated to the intervention arm, and invited to screening. The control arm will receive no intervention. All men in the screening arm will be offered a serum PSA determination. Those with PSA of 3 ng/ml or higher will have an additional multi-kallikrein panel and those with indications of increased risk of clinically relevant prostate cancer will undergo mpMRI. Men with a malignancy-suspect finding in MRI are referred to targeted biopsies. Screening interval is 6 years for men with baseline PSA < 1.5 ng/ml, 4 years with PSA 1.5-3.0 and 2 years if initial PSA > 3. The main outcome of the trial is prostate cancer mortality, with analysis at 10 and 15 years. The statistical power is sufficient for detecting a 28% reduction at 10 years and 22% at 15 years. The proposed study has the potential to provide the evidence to justify screening as a public health policy if mortality benefit can be sustained with substantially reduced overdiagnosis.
目前基于 PSA 的前列腺癌筛查的证据表明可以降低特定病因死亡率，但存在大量过度诊断。最近，除了 PSA 之外，多种激肽释放酶作为生物标志物，以及多参数磁共振成像（mpMRI）用于活检决策，这些在检测临床相关前列腺癌方面的新进展为改善筛查结果提供了机会，特别是减少过度诊断和提高对潜在致命癌症的特异性。一项基于人群的随机筛查试验即将开始，共有 67000 名年龄在 55-67 岁的男性入组。其中四分之一的男性将被分配到干预组，并邀请他们进行筛查。对照组将不进行干预。筛查组的所有男性都将接受血清 PSA 测定。PSA 水平为 3ng/ml 或更高的男性将进行额外的多激肽组检测，PSA 水平提示有临床相关前列腺癌风险增加的男性将进行 mpMRI。MRI 有恶性肿瘤可疑发现的男性将接受靶向活检。对于基线 PSA<1.5ng/ml 的男性，筛查间隔为 6 年；PSA 为 1.5-3.0ng/ml 的男性，筛查间隔为 4 年；PSA 初始值>3ng/ml 的男性，筛查间隔为 2 年。该试验的主要结局是前列腺癌死亡率，分析时间为 10 年和 15 年。该统计效力足以检测到 10 年时降低 28%，15 年时降低 22%。如果能够通过显著减少过度诊断来维持死亡率的获益，那么这项研究有可能提供支持将筛查作为公共卫生政策的证据。
