《JAMA》子刊：靶向筛查能减少六分之一的前列腺癌死亡

编辑翻译：奇奇

译文校对：菁菁

本文献发表在2021年3月最新的《美国医学会杂志》（JAMA Network Open）上。文献中伦敦大学学院（UCL）的研究人员发现，特定因素的前列腺癌靶向筛查可以降低该疾病的死亡率和过度诊断。

以伦敦大学学院（UCL）的科研人员为首的新研究发现，在针对有遗传性前列腺癌的男性的一项全国性筛查项目中，侵入性活检前进行血液检测和MRI扫描能够预防六分之一的前列腺癌死亡，并显著地减少过度诊断。

前列腺腺泡腺癌（一种最为常见的前列腺癌）的显微镜影像。

前列腺癌是男性中最常见的癌症。在英国，每天诊断出约130例新病例，每年有超过10000的男性因该疾病而死亡。但是，与乳腺癌和宫颈癌不同，英国目前没有针对前列腺癌的全国性筛查计划。

目前，在疑似前列腺癌患者的男性血液检测中发现其前列腺特异性抗原（PSA）水平升高。根据UCL主导的精准实验，国家临床卓越研究所（NICE）的指导方针也建议所有PSA结果呈阳性的男性在活检前进行MRI扫描，因为事实证明这样做可以更好地识别、检测侵略性癌症，同时减少了过度诊断和对无关紧要的癌症的不必要治疗。

在此基础上，研究人员说最近发现的、可预测前列腺癌风险的遗传标记，能够作为PSA检测和MRI扫描的补充诊断方法。一种尚未广泛应用的多基因检测可以识别出具有高危前列腺癌基因（生物标记）的个体，并能帮助预测个体可能开始从筛查中受益的年龄。

Tom Callender博士（UCL医学分部）是这项研究的主要作者，他说：“在导致男性死亡的各种癌症中，前列腺癌是主要的病种。没有筛查计划是因为筛查的危害被认为大于其益处。但是那些遗传风险较高的人更有可能从筛查中受益，而且受到伤害的可能性也更小。较为传统的前列腺癌筛查手段，是对所有55岁到69岁男性进行四年一次的普查。本次研究则提出基于年龄和遗传档案对高风险人群进行筛查。为了分析利弊和衡量成本效益，我们比较了两种方法的效果。在前列腺癌筛查计划的背景下，我们还调查了活检前进行MRI扫描对那些PSA血液检测呈阳性的患者有什么影响。”

发表在JAMA Network Open上的这项建模研究中，研究人员创建了一个包括450万个男性的模型，模型数量代表了英国55到69岁的男性数量。使用这一模型，引入基于年龄和特定风险的筛查计划，研究人员模拟了健康结果。

研究人员模拟了一项基于年龄因素的筛查计划，该计划中所有55到69岁的男性每四年接受一次PSA检查。若检查结果呈阳性，则进行MRI检查，必要的话也会进行活检。

基于特定风险因素的模拟筛查计划中，如果男性的风险达到某个阈值，则需要进行PSA检测（有必要的话也进行MRI和活检），该风险由男性的年龄和多基因风险评分（遗传档案）决定。

与未筛查相比，该健康结果是基于普遍年龄和更具针对性地使用一些风险阈值的筛查，包括了预防前列腺癌死亡、避免不必要的诊断，以及筛查成本（成本效益衡量）和PSA血液检测呈阳性的患者活检前是否使用MRI扫描。

研究人员总结说，产生最大收益的方案是在未来10年对有3.5%风险患前列腺癌的男性进行筛查，也就是大概一半的55到69岁的男性。这一计划可以降低16%的前列腺癌死亡率——即近六分之一的死亡率，并减少27%的过度诊断。与筛查所有55到69岁的男性相比，筛查这一阈值（3.5%）的男性将更具成本效益。

对该年龄组的所有男性进行筛查(基于年龄的筛查途径)可以最大程度地降低前列腺癌死亡率（20%）。然而，基于特定风险的靶向筛查也可以使死亡率降低类似水平，同时使癌症过度诊断(最终无害的癌症)数量减少70%(取决于使用的风险阈值)，所需的活检数量也减少约三分之一。

UCL应用健康研究所的资深作者Nora Pashayan教授说：“在血液筛查呈阳性的男性中，我们发现，活检前在MRI筛查中使用个人遗传档案和诊断途径，可以减少不必要的过度诊断，同时可以通过筛查发现早期的、可治愈的前列腺癌，来降低死亡率。”

论文合著者、UCL医学院院长Mark Emberton教授说：“我们的研究表明，在前列腺癌筛查计划中，引入遗传风险因素并使用MRI诊断方法，可能减少16%到20%的前列腺癌死亡率，这为进一步研究该筛查计划在现实世界的临床试验铺平了道路。”

英语原文

Targeted Screening for Prostate Cancer Could Prevent One in Six Deaths

A national screening program targeted at those men who are genetically predisposed to prostate cancer, and involving a blood test and MRI scan before an invasive biopsy, could prevent one in six prostate cancer deaths and significantly reduce over-diagnosis, finds a new study led by UCL researchers.

Prostate cancer is the most common form of cancer in men with around 130 new cases diagnosed in the UK every day and more than 10,000 men a year dying as a result of the disease. However, unlike breast and cervical cancer there is currently no national screening program for this disease in the UK.

Currently, men suspected of having prostate cancer have a blood test that detects raised levels of the prostate-specific antigen(PSA). Following the UCL-led PRECISION trial, the National Institute of Clinical Excellence (NICE) guidelines, also now advises that all men with a positive PSA result have an MRI scan prior to biopsy—as this has been shown to better distinguish and increase detection of aggressive cancers whilst reducing over-diagnosis and unnecessary treatment of insignificant cancers.

Building on this, researchers say recently discovered genetic markers that predict prostate cancer risk could also complement a PSA test and MRI scan. A polygenic test—not yet widely available—canidentify individuals with high-risk prostate cancer genes (biomarkers) and help predict when an individual is likely to start to benefit from screening.

Explaining the study, lead author Dr. Tom Callender (UCL Division of Medicine) said,"Prostate cancer is a leading cause of death from cancer amongst men, but there is no screening program because the harms of screening are considered to outweigh the benefits.However those at higher genetic risk are more likely to benefit from screening and less likely to be harmed.For this benefit-harm and cost-effectiveness analysis, we asked how effective a four-yearly PSA screening for all men aged 55 to 69 would be versus more targeted checks for those at higher risk of the disease based on their age and genetic profile.We also asked, what the impact would be of those with a positive PSA blood test having an MRI scan before a biopsy, in the context of a prostate cancer screening program."

In this modelling study, published in JAMA Network Open, researchers created a hypothetical cohort of 4.5 million men, representing the number of men aged 55 to 69 in England, and simulated the health outcomes of introducing either "age-based" and "risk-tailored" screening programs into this population.

The age-based diagnostic pathway modelled a screening program in which all men aged between 55 and 69 would receive a PSA test every four years, and if the test was positive this would be followed by MRI and, if required, a biopsy.

The risk-tailored pathway modelled a screening program in which men would get a PSA test (followed by MRI and biopsy if required) if and when their risk—determined by their age and polygenic risk score (genetic profile) - reached a certain threshold.

Health outcomes, including prostate cancer deaths prevented and unnecessary diagnoses averted, along with screening costs (i.e the cost effectiveness measure) were compared for no screening, universal age-based screening and more targeted risk-based screening using a range of risk thresholds, both with and without the use of an MRI scan before biopsy in those with a positive PSA blood test.

The scenario generating the most benefits, the researchers concluded, would be to screen men with a 3.5% risk of getting prostate cancer over the next 10 years—that is, roughly half of all men aged 55 to 69. Such a program could prevent up to 16% of prostate cancer deaths—nearly one in six deaths and reduce overdiagnosis by 27%. Screening men at this threshold (3.5%) would also be morecost-effective than screening all men aged 55 to 69.

Screening all men in that age group (the age-based screening pathway) would result in themost prostate cancer deaths prevented (20%). However, targeted risk-based screening prevents a similar number of deaths whilst reducing the number of over-diagnosed cancers (those cancers that end up being harmless) by up to 70%(depending on the risk threshold used) and the number of biopsies needed by approximately one-third.

Senior author, Professor Nora Pashayan, (UCL Applied Health Research), said: "In men with a positive screening blood test, we found that using an individual' sgenetic profile alongside a diagnostic pathway that uses MRI scanning before biopsy, could reduce unnecessary diagnoses whilst preventing deaths from prostate cancer by detecting the cancers at an early, curable stage."

Co-author, Professor Mark Emberton, UCL Dean of the Faculty of Medical Sciences: "Our study shows that screening for prostate cancer—which could save between 16% and 20% of prostate cancer deaths—might be possible with targeted screening using genetic risk and MRI as part of the diagnostic pathway. This paves the way for further clinical trials to study the real-world implementation of sucha screening program."

参考文献

More inThomas Callender, Mark Emberton, Stephen Morris, PaulPharoah, Nora Pashayan, The impact of MRI prior to biopsy on age-based andrisk-tailored screening for prostate cancer: A benefit-harm andcost-effectiveness analysis, JAMA Network Open (2021). DOI:10.1001/jamanetworkopen.2020.37657

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