The recent approval of the poly(ADP-ribose) polymerase (PARP) inhibitor olaparib for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) harbouring pathogenic variants of BRCA2 or BRCA1 marks the start of molecularly guided precision medicine in prostate cancer. In parallel with this approval comes the need to embed molecular diagnostics in the clinical management of patients with mCRPC. To date, however, there are no established protocols in Belgium for the use of mutation testing in this setting. This article will therefore provide practical guidance for sample preparation and handling, pre-analytic processing, and pathogenic variant analysis in mCRPC. Across the different phases of this process, a multidisciplinary approach involving urologists, oncologists, radiologists, pathologists, molecular biologists, technicians, nurses, and geneticists will be key to safeguard adequate sample selection to perform molecular analyses at the time of metastatic disease. It will also facilitate high-quality molecular testing with a minimal failure rate. Only by optimising this process will physicians be able to adequately select mCRPC patients that are most likely to benefit from PARP inhibition, or other future targeted therapies, allowing to use these agents in the correct patient groups.

(BELG J MED ONCOL 2022;16(7):343–54)