Prostate Cancer Prevention Clinic for Men with Risk of Familial Prostate Cancer

在国家癌症预防研究生院内，德国癌症援助(DKH)与DKFZ核心单位(国家癌症预防中心)合作，资助了杜塞尔多夫大学为有家族风险的男性新设立的前列腺癌预防诊所。这是一家独特的、也是第一家此类门诊诊所，每年将包括约50-70名前列腺癌(PCA)高危男性(2023-2026年)，并提供专门的诊断(如多参数核磁共振、心理测量测试、实验室和基因分析)。目的是通过建立个性化的风险评分和连续的风险适应监测，更好地管理患者的S焦虑。DKH正在资助一名研究生，他将评估在这次风险咨询中针对前列腺癌高危男性进行的关于焦虑发展的心理测量测试。计划中的基因分析不在资助范围内，但将是制定个人评分和适应风险的早期检测的关键。杜塞尔多夫大学医院(CIO-D作为综合肿瘤学中心的一部分，CIO-ABCD)从人员方面为这家门诊诊所提供支持。所有男性都将接受遗传咨询，包括系谱分析、临床调查和多参数专门的前列腺核磁共振成像。在知情同意后，所有男性(指标患者或高危男性)将在第一步接受专门的、众所周知的PCa相关基因的诊断小组测序。然而，到目前为止，只有几个基因被认为与前列腺癌有关(例如BRCA1、BRCA2、HOXB13)。只有15%-20%的受影响个体被确认携带这些基因之一的突变。很可能还有大量的其他前列腺癌风险基因，而且到目前为止对前列腺癌的遗传基础的了解还很初级。因此，有必要在第二步对少数几个PCA风险基因没有致病突变的男性进行进一步的血液和/或肿瘤的遗传分析(外显子组测序、基因组测序和转录组分析)，目的是阐明潜在的遗传变化，从而深刻理解肿瘤发生的机制。只有这些知识才能明确男性/他们的家庭成员的风险，并将他们转移到适当的早期诊断，这是我们前列腺癌风险咨询的目标。为了明确基于遗传分析和临床/影像检查的风险，将为已知和新发现的基因突变建立男性前列腺癌患者的基因-表型相关性。最后，将开发一个评分系统来计算PCa风险增加的男性的个性化风险，并随后进行测试和评估。

Within the National Cancer Prevention Graduate School, the German Cancer Aid (DKH) funds a newly established Prostate Cancer Prevention Clinic for men with familial risk at Düsseldorf University in collaboration with the DKFZ core unit (National Cancer Prevention Center). This is a unique and first of its kind outpatient clinic which will include about 50-70 men at risk for prostate cancer (PCA) per year (2023-2026) and offer specialized diagnostics (like multiparametric MRI, psychometric tests, laboratory and genetic analysis). Aim is a better management of patient´s anxiety by establishing an individualized risk score with consecutive risk-adapted monitoring. DKH is funding a graduate student who will evaluate the psychometric tests administered in this risk consultation for men at risk for prostate cancer with respect to the development of anxiety. The planned genetic analyses are not covered by funding, but will be the key for development of an individual score and risk-adapted early detection. The University Hospital Düsseldorf (CIO-D as part of the Center for Integrated Oncology, CIO-ABCD) supports this outpatient clinic in terms of personnel. All men will receive genetic counselling including pedigree analyses, clinical investigations and multiparametric specialized MRI of the prostate. After informed consent, all men (index patients or men at risk) will receive diagnostic panel sequencing of dedicated, well-known PCA-related genes in a first step. To date, however, only a few genes have been identified for which an association with PCA is postulated (e.g. BRCA1, BRCA2, HOXB13). Only 15-20% of affected individuals are identified to carry a mutation in one of these genes. It is likely that there are a large number of other PCA risk genes and the understanding of the genetic basis of PCA is only rudimentary to date. It is therefore essential to perform further genetic analyses of blood and/or tumor (exome sequencing, genome sequencing and transcriptome analyses) in men without pathogenic mutations in the few PCA risk genes in a second step with the aim of elucidating the underlying genetic alterations and thus gaining a profound understanding of the mechanisms of tumorigenesis. Only this knowledge will allow to specify the risk for the men/their family members and to transfer them to an appropriate early diagnosis, which is the aim of our prostate cancer risk consultation. To specify the risk based on genetic analyses and clinical/imaging examinations, a genotype-phenotype correlation for men with PCA will be established for mutations in known as well as in newly identified genes. Finally, a scoring system will be developed to calculate a personalized risk for men at increased risk of PCA and subsequently tested and evaluated.