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

Niven Mehra1, Iris Kloots1, Michiel Vlaming2

  • 1Department of Medical Oncology, Radboud UMC, Nijmegen, The Netherlands.

European Urology Open Science
|March 6, 2023
PubMed
Summary

Dutch experts reached consensus on genetic testing for prostate cancer (PCa), recommending specific indications for germline and tumor testing based on disease stage and family history. These guidelines aim to improve genetic counseling and molecular testing strategies for PCa management.

Keywords:
BRCA1/2Castration-resistant prostate cancerDNA damage repairGenetic counsellingGermline genetic testingMismatch repairProstate cancerTumour genetic testing

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Area of Science:

  • Oncology
  • Genetics
  • Medical Diagnostics

Background:

  • Germline and tumor genetic testing in prostate cancer (PCa) is increasingly utilized, but clear guidelines for its application across different disease stages are lacking.
  • Defining appropriate indications and understanding the clinical implications of genetic testing for PCa patients and carriers are crucial for effective management.

Purpose of the Study:

  • To establish a consensus among a Dutch multidisciplinary expert panel regarding the indications and application of germline and tumor genetic testing in prostate cancer.
  • To provide guidance on when and for which prostate cancer patients genetic testing is appropriate, considering disease stage and family history.

Main Methods:

  • A modified Delphi method was employed, involving 39 Dutch specialists in PCa management through two voting rounds and a virtual consensus meeting.
  • Consensus was defined as agreement among at least 75% of the panelists, with appropriateness assessed using the RAND/UCLA appropriateness method.

Main Results:

  • Consensus was achieved on 44% of the multiple-choice questions. For familial PCa or BRCA-related hereditary cancer, prostate-specific antigen follow-up was deemed appropriate. Active surveillance was recommended for low-risk localized PCa with a family history, unless the patient is a BRCA2 germline pathogenic variant carrier.
  • Germline and tumor genetic testing are not recommended for nonmetastatic hormone-sensitive PCa without a relevant cancer family history. Tumor genetic testing is most appropriate for identifying actionable variants, while its role in germline testing remains uncertain.
  • Consensus was not reached on the timing and panel composition for tumor genetic testing in metastatic castration-resistant PCa. Key limitations include a lack of scientific evidence for some topics, making recommendations partly opinion-based, and a small number of experts per discipline.

Conclusions:

  • The outcomes of this Dutch consensus meeting offer valuable guidance for genetic counseling and molecular testing strategies in prostate cancer care.
  • These recommendations aim to standardize the use of genetic testing, ensuring it is applied appropriately to optimize patient management and treatment decisions in PCa.