4 associated with an approximately threefold increased risk of developing prostate cancer. Other genes that are associated with hereditary prostate cancer include CHEK2, NBN, ATM, PALB2, BRIP1, RAD51C, RAD51D and TP53, even though the exact risk gures are uncertain. It is important to note, that to date, not all the prostate cancer-causing genes have been identied. Therefore, if a person has a strong family history and many individuals affected with prostate and/or other cancers, a negative (normal) genetic test cannot exclude a hereditary cancer syndrome. In these families the genetic counsellor will use the family history information to determine the cancer risks and make surveillance recommendations. Motivations for genetic testing in prostate cancer Recent International guidelines have introduced recommendations for the inclusion of genetic testing in the assessment of men diagnosed with prostate cancer. In Box 1, you will nd a summary of the latest guidelines from the National Comprehensive Cancer Network (NCCN) and the European Association of Urology (EAU). If an individual meets the outlined criteria, it is highly probable that the cost associated with genetic testing will be covered by local medical insurers. This typically requires a motivation letter, providing a compelling rationale for the necessity of genetic testing, from their genetic counsellor, urologist and/or oncologist. Understanding a patient's genetic status upon being diagnosed with prostate cancer is of paramount importance as it plays a pivotal role in tailoring the most suitable treatment and management plan. For individuals with genetic prostate cancer, the stakes are higher, as they face a potentially more aggressive form of the disease and decreased survival rates when early detection is missed. Additionally, they have an elevated risk of cancer recurrence, even following curative treatments initiated for early-stage disease, necessitating a proactive approach to management. In the current era of precision medicine, treatment efcacy is increasingly determined by an individual's unique genetic make-up. Notably, several FDAapproved gene-targeted therapies are now available, primarily benetting metastatic prostate cancer patients. These therapies include PARP-inhibitors and immunotherapies. PARP-inhibitors have exhibited promising results, particularly in men who carry mutations in DNA repair genes such as BRCA1, BRCA2, ATM, CHEK2, NBN, PALB2, RAD51C, RAD51D. Conversely, the immunotherapies are designed to target the Lynch syndrome genes. It is important to note that genetic tests to determine therapy encompass both germline and somatic testing. Germline testing is done on a blood or saliva sample and looks at the genetic mutations a person is born with and carry in every cell of your body. Somatic testing examines the cancer cells to identify genetic mutations acquired due to external factors, such as lifestyle and environmental inuences. Importantly, mutations in somatic cells are not inherited and cannot be passed on to subsequent generations. Furthermore, genetic testing yields insights into the risk of developing a second prostate or other types of cancers. An inherited cancer syndrome, contingent upon the specic gene involved, can predispose individuals to various other cancer types. Knowing which other areas of the body are at risk allows the healthcare providers the opportunity to put the most appropriate surveillance plan in place to either prevent or detect cancer at an early manageable stage. For instance, a man with prostate cancer carrying a BRCA2 genetic mutation, also faces an increased risk of breast, melanoma and pancreatic cancer. To address the breast cancer risks he may be advised to conduct monthly self-examinations and undergo annual clinical examinations of the chest area starting from the age of 35 years. Annual full bodyskin examinations by a dermatologist can help mitigate melanoma risk, while additional pancreatic cancer screening is recommended from the age of 50 years if a strong family history of this cancer type is present. Genetic testing holds signicance not only for the individual diagnosed with cancer, but also for their children and other blood-related family members. When a man carries a cancer-causing gene variant, each of his children has a 50% chance of inheriting it. This information is crucial for both his sons and daughters, as these gene variants often include a heightened risk of breast and ovarian cancer. Equipped with this knowledge, the affected individual's children, siblings, and other relatives can implement essential cancer-risk management strategies to safeguard against these malignancies. It's imperative for unaffected family members to have genetic counselling before undergoing genetic testing to ensure that they fully comprehend the implications of the results. Importantly, genetic testing does not impact the insurance policies and premiums of individuals diagnosed with cancer. However, it may lead to certain exclusions and/or increased premiums for unaffected individuals. Therefore, it's advisable for unaffected individuals to secure their life and other insurance policies before undergoing genetic testing. The role of genetic counsellors in prostate cancer care Genetic counsellors are allied health care professionals that are trained in the principles and practices of genetic testing, hereditary cancer assessment and informed decision-making for genetic testing. They assess an individual's personal and family medical history to offer advice on whether genetic testing is appropriate. To promote informed decision-making, they provide information on the risks, limitations and benets of each genetic testing option as genetic testing is not always straightforward. Each genetic test has limitations with regards to the technology that is used and cannot UROLOGY, URO-ONCOLOGY AND SEXOLOGY UPDATE
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