MICA: The exploitation of a novel image-based risk stratification tool in early prostate cancer - the Re-IMAGINE Consortium

背景：每8个男性中就有1个会患前列腺癌，而且风险随着年龄的增长而增加。大多数人不会因此而死，但有些人会。我们鉴别哪些人的癌症会降低他们的生活质量或数量的能力仍然很差。在现代医学中，没有其他地方比过度诊断、过度治疗、漏诊和不良风险分层的错误更极端。这四种错误——每年仅在欧洲就直接影响到100万接受前列腺活检的男性——导致所采用的治疗几乎没有益处，使男性遭受重大的终身伤害，浪费了宝贵的医疗资源。目标：我们的Re-IMAGINE联盟成立的目的是为了纠正这四个关键错误。我们将第一次能够将癌症中潜在的分子变化与最先进的成像技术结合起来。这将使我们能够预测个体的前列腺癌状态（低、中、高风险），而无需活检。它还将使我们能够预测哪些前列腺癌可能随着时间的推移而发展，哪些不会——这是迄今为止我们在很大程度上无法做到的。通过这样做，男性将接受更少但更好的活组织检查，改善风险分层，适当的治疗分配，更多的益处，更少的伤害和更具成本效益的护理。方法：我们将通过建立患者、倡导组织、临床医生、成像专家、分子生物学家、方法学家和广泛的工业合作伙伴之间的既定伙伴关系来实现这一目标。Re-IMAGINE的愿景是建立在我们最近发表的研究成果之上的，该研究表明，与标准的前列腺活检相比，前列腺磁共振成像（MRI）在识别男性风险方面100%更好，而且没有遗漏任何潜在致命疾病的男性。MRI现在肯定会成为未来早期前列腺癌风险分层过程的基石。然而，我们对MRI与体内其他标志物的结合使用知之甚少。通过与患者和倡导团体合作，我们已经开发了几个工作链（WS），这将使我们能够实现我们的目标：WS1将创建第一个通过基于mri的途径接受前列腺癌诊断的男性组（队列）。在得到适当同意后，这些人将捐献一些组织、血液和尿液用于标志物分析。他们将从伦敦三个拥有高质量核磁共振成像的主要中心招募。WS2将在癌症不太常见的人群中测试核磁共振成像的表现——在没有做过PSA测试的男性中。这将使我们能够预测社区中处于危险中的男性的确切比例。这些工作流程将产生大量数据（临床信息、成像数据以及来自血液、组织和尿液中的标记物的信息）。我们将使用安全的数据仓库将每个患者的所有数据组合起来，并使用先进的数学技术进行分析。如此复杂的项目将需要高水平的项目管理和协调。这将通过在现有和富有成效的合作的基础上实现。由于它的雄心、可能的影响和潜在的积极破坏，我们很高兴早期的开发工作是由患者及其家属告知和推动的，在某些特定情况下（WS2）是由公众推动的。在数据收集、分析和传播期间，将加强患者和公众的这种参与。影响：Re-IMAGINE将把早期前列腺癌的管理从一个不精确和不确定是常态的时代转变为一个任何患者都可以期望并受益于对自己风险的精确预测和更好的护理的时代。

Background: One in eight men will develop prostate cancer and the risk increases with age. Most will not die of it, but some do. Our ability to identify those men whose cancer will decrease either their quality or quantity of life remains poor. Nowhere else in modern medicine are the errors of over-diagnosis, over-treatment, missed-diagnoses and poor risk-stratification more extreme. These four errors - which impact directly on the 1million men who undergo prostate biopsy each year in Europe alone - result in the application of treatments that have little or no benefit, leave men suffering with significant life-long harms and waste valuable healthcare resources. Aims:Our Re-IMAGINE Consortium has been created to undertake discovery that will correct these four key errors. We will, for the first time, be able to combine the underlying molecular changes in the cancer with state-of-the-art imaging. This will allow us to predict prostate cancer status for the individual (low, medium or high risk) without recourse to biopsy. It will also allow us to predict which prostate cancers are likely to progress over time and which are not - something that has largely eluded us so far. By doing so, men will be subject to fewer but better biopsies, improved risk stratification, appropriate treatment allocation, more benefit, less harm and more cost-effective care. Methods:We will achieve this by building on established partnerships between patients, advocacy organisations, clinicians, imaging experts, molecular biologists, methodologists and a broad range of industrial partners. The vision of Re-IMAGINE is built on our recently published work showing that magnetic resonance imaging (MRI) of the prostate was 100% better at identifying men at risk compared to the standard prostate biopsy, and moreover missed no men with potentially fatal disease. MRI is now certain to become the future cornerstone of the risk-stratification process for men at risk of early prostate cancer. However, we know very little about the use of MRI in combination with other markers in the body.Through working with patients and advocacy groups, we have developed several work strands (WS) that will allow us to realise our aims:WS1 will create the first group (cohort) of men who receive a prostate cancer diagnosis by means of an MRI-based pathway. These men will, after appropriate consent, donate some tissue, blood and urine for marker analysis. They will be recruited from 3 major centres in London that have high quality MRI in place. WS2 will test the performance of MRI in a population where cancer is less common - in men who have not had a PSA test. This will allow us to predict the exact proportion of men at risk within the community. These work streams will generate a lot of data (clinical information, imaging data, as well as information from markers in blood, tissue, and urine). We will combine all this data for each patient using a secure data warehouse and analyse it using advanced mathematical techniques. Such a complex project will require high levels of project management and coordination. This will be achieved by building on existing and fruitful collaborations. Due to its ambition, likely impact and potential for positive disruption we are pleased that the early development work was both informed and driven by patients and their families and in some specific instances (WS2) by the public. This patient and public involvement will intensify during the period of data gathering, analysis and dissemination. Impact: Re-IMAGINE will transform the management of early prostate cancer from an era in which imprecision and uncertainty was the norm to one in which any patient can expect - and benefit from - a precise prediction of his own risk and better care as a result.