Hereditary urological cancer

Genetic testing is clinically relevant for the following indications, including but not limited to:

• Kidney cancer with early onset, multifocal or bilateral disease, characteristic histology or a supportive family history.
• Suspected Birt-Hogg-Dubé syndrome, with fibrofolliculomas, pulmonary cysts with spontaneous pneumothorax, or renal tumours.
• Suspected hereditary leiomyomatosis and renal cell cancer, with cutaneous or uterine leiomyomas and aggressive renal tumours.
• Men with metastatic, high-risk or very-high-risk prostate cancer, or a relevant personal or family cancer history, per the

Testing is typically requested by urologists, medical oncologists, clinical geneticists and nephrologists.

Germline testing is used when clinical or family features suggest an inherited cause, and it guides treatment decisions. For example, in a multicentre cohort of 692 men with metastatic prostate cancer, inherited DNA-repair gene variants were identified in 11.8%, informing treatment and family counselling.

A pathogenic or likely pathogenic variant establishes the specific molecular diagnosis, identifying the causative gene and hereditary syndrome. A variant of uncertain significance (VUS) is an unclear finding: current evidence is insufficient to classify it as likely benign or likely pathogenic, and reanalysis can be offered after a few years as evidence accumulates. In other cases, no pathogenic variant is detected in the analysed genes. The presence of a pathogenic variant cannot, however, be entirely excluded: the causative change may lie in a gene not yet linked to the condition, or in a regulatory region that current methods cannot reliably capture.

Each variant is classified according to criteria.

When a pathogenic or likely pathogenic variant is identified, organ-specific surveillance and risk-reducing management can be established, and treatment selection can be informed where targeted options apply. Where syndromic features are present, specialist multidisciplinary care can be coordinated. A confirmed germline finding carries familial implications, enabling cascade and predictive testing of at-risk relatives.

is an important part of the testing process. It helps patients and families understand the test, interpret results, and make well-informed medical decisions, and it supports physicians in delivering informed care. Availability of genetic counselling services may vary by country. Please to check out access in your region.

Testing is performed using based multi-gene panels.

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• Giri VN, Knudsen KE, Kelly WK, Cheng HH, Cooney KA, Cookson MS, et al. Implementation of Germline Testing for Prostate Cancer: Philadelphia Prostate Cancer Consensus Conference 2019. J Clin Oncol. 2020 Aug 20;38(24):2798-2811. doi: 10.1200/JCO.20.00046. Epub 2020 Jun 9. PMID: ; PMCID: PMC7430215.
• Pritchard CC, Mateo J, Walsh MF, De Sarkar N, Abida W, Beltran H, et al. Inherited DNA-Repair Gene Mutations in Men with Metastatic Prostate Cancer. N Engl J Med. 2016 Aug 4;375(5):443-53. doi: 10.1056/NEJMoa1603144. Epub 2016 Jul 6. PMID: ; PMCID: PMC4986616.