Practical Guidance on Establishing a Molecular Testing Pathway for Alterations in Homologous Recombination Repair Genes in Clinical Practice for Patients with Metastatic Prostate Cancer.

Prostate cancer is a molecularly heterogeneous disease that is amenable to diagnostic testing to identify patients potentially eligible for personalised treatments inform familial risk and provide relevant information about potential prognosis. Several guidelines support the integration of genomic testing in a shared decision-making framework so that both health care professionals (HCPs) and patients are involved in determining the best treatment approach.

To review current guidelines on molecular diagnostic testing for homologous recombination repair (HRR) gene alterations in patients with metastatic prostate cancer, with the aim of providing practical considerations for effective guideline implementation and establishment of an appropriate pathway for molecular diagnostic testing.

We undertook a nonsystematic narrative review of the literature using PubMed to identify current guidelines and recommendations on molecular diagnostic testing for BRCA and/or homologous recombination repair gene alterations (HRRm) in patients with prostate cancer. In addition, selected articles that included BRCA/HRRm testing in clinical trials in metastatic castration-resistant prostate cancer and real-world evidence were also evaluated. Websites for relevant societies were reviewed for molecular diagnostic guidelines not published on PubMed.

Our review of guidelines published by several international societies that include molecular testing in prostate cancer identified variations in molecular testing approaches. The review of testing approaches used in clinical trials and real-world settings also highlighted several aspects that require improvement. Therefore, we compiled practical guidance for establishing an appropriate BRCA/HRR mutation testing pathway.

While there are several challenges to molecular testing and interpretation of test results that require enhancement, a multidisciplinary team approach will empower HCPs and their institutions to improve on or initiate their own molecular testing pathways. This in turn will lead to improvements in management strategies for patients with metastatic prostate cancer, for whom better treatment outcomes is a significant unmet need.

Establishing a molecular testing pathway in clinical practice for patients with metastatic castration-resistant prostate cancer will lead to fairer and more equal access to personalised treatments. This should lead to better outcomes, particularly for patients whose disease has spread to other areas of the body.

European urology oncology. 2023 Sep 13 [Epub ahead of print]

Martin Schostak, Angela Bradbury, Alberto Briganti, David Gonzalez, Leonard Gomella, Joaquin Mateo, Frédérique Penault-Llorca, Albrecht Stenzinger, Alexander W Wyatt, Anders Bjartell

Department of Urology, Urooncology, Robot-assisted and Focal Treatment, University Hospital Magdeburg, Magdeburg, Germany. Electronic address: ., Perelman Center for Advanced Medicine, Philadelphia, PA, USA., Vita-Salute San Raffaele University, Milan, Italy., Patrick G. Johnston Centre for Cancer Research, Queen's University, Belfast, UK., Department of Urology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA., Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron University Hospital, Barcelona, Spain., University Clermont Auvergne, Centre Jean Perrin, Clermont-Ferrand, France., Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany., Vancouver Prostate Centre, University of British Columbia, Vancouver, Canada., Department of Urology, Skåne University Hospital, Malmö, Sweden; Department of Translational Medicine, Lund University, Lund, Sweden.