Genetic Aspects and Molecular Testing in Prostate Cancer: A Report from a Dutch Multidisciplinary Consensus Meeting

• Published in: European urology open science (Online) Vol. 49; pp. 23 - 31
• Main Authors: Mehra, Niven, Kloots, Iris, Vlaming, Michiel, Aluwini, Shafak, Dewulf, Els, Oprea-Lager, Daniela E., van der Poel, Henk, Stoevelaar, Herman, Yakar, Derya, Bangma, Chris H., Bekers, Elise, van den Bergh, Roderick, Bergman, Andries M., van den Berkmortel, Franchette, Boudewijns, Steve, Dinjens, Winand N.M., Fütterer, Jurgen, van der Hulle, Tom, Jenster, Guido, Kroeze, Leonie I., van Kruchten, Michel, van Leenders, Geert, van Leeuwen, Pim J., de Leng, Wendy W.J., van Moorselaar, R. Jeroen A., Noordzij, Walter, Oldenburg, Rogier A., van Oort, Inge M., Oving, Irma, Schalken, Jack A., Schoots, Ivo G., Schuuring, Ed, Smeenk, Robert J., Vanneste, Ben G.L., Vegt, Erik, Vis, André N., de Vries, Kim, Willemse, Peter-Paul M., Wondergem, Maurits, Ausems, Margreet
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.03.2023; Elsevier
• Subjects: BRCA1/2; Castration-resistant prostate cancer; DNA damage repair; Genetic counselling; Germline genetic testing; Mismatch repair; Prostate Cancer; Tumour genetic testing; Urology; Castration-resistant prostate cancer; BRCA1/2; DNA damage repair; Germline genetic testing; Mismatch repair; Tumour genetic testing; Genetic counselling; Prostate cancer
• ISSN: 2666-1683; 2666-1691; 2666-1683
• DOI: 10.1016/j.euros.2022.11.011

A Dutch multidisciplinary expert panel favoured tumour-first testing in metastatic prostate cancer (PCa) to identify actionable variants. Consensus was reached to trigger cascade germline genetic testing in metastatic PCa patients having BRCA1/2 tumour pathogenic variants. Germline and tumour genetic testing in prostate cancer (PCa) is becoming more broadly accepted, but testing indications and clinical consequences for carriers in each disease stage are not yet well defined. To determine the consensus of a Dutch multidisciplinary expert panel on the indication and application of germline and tumour genetic testing in PCa. The panel consisted of 39 specialists involved in PCa management. We used a modified Delphi method consisting of two voting rounds and a virtual consensus meeting. Consensus was reached if ≥75% of the panellists chose the same option. Appropriateness was assessed by the RAND/UCLA appropriateness method. Of the multiple-choice questions, 44% reached consensus. For men without PCa having a relevant family history (familial PCa/BRCA-related hereditary cancer), follow-up by prostate-specific antigen was considered appropriate. For patients with low-risk localised PCa and a family history of PCa, active surveillance was considered appropriate, except in case of the patient being a BRCA2 germline pathogenic variant carrier. Germline and tumour genetic testing should not be done for nonmetastatic hormone-sensitive PCa in the absence of a relevant family history of cancer. Tumour genetic testing was deemed most appropriate for the identification of actionable variants, with uncertainty for germline testing. For tumour genetic testing in metastatic castration-resistant PCa, consensus was not reached for the timing and panel composition. The principal limitations are as follows: (1) a number of topics discussed lack scientific evidence, and therefore the recommendations are partly opinion based, and (2) there was a small number of experts per discipline. The outcomes of this Dutch consensus meeting may provide further guidance on genetic counselling and molecular testing related to PCa. A group of Dutch specialists discussed the use of germline and tumour genetic testing in prostate cancer (PCa) patients, indication of these tests (which patients and when), and impact of these tests on the management and treatment of PCa.