Expert practical recommendations for optimising tumour and germline testing of homologous recombination repair gene mutations in metastatic prostate cancer.

With the approval of PARP inhibitors (PARPi), both as monotherapy and in combination with androgen receptor signalling inhibitors (ARSi), for metastatic castration-resistant prostate cancer (mCRPC) and their rapid development in earlier disease settings, there is an urgent need to integrate homologous recombination repair (HRR) testing into daily clinical practice to identify patients who may benefit from these therapies and to improve patient management. Alterations in HRR genes are found in approximately 15-30% of patients with mCRPC and are associated with poor prognosis. In addition, some alterations are hereditary; therefore, testing also has implications for the identification of hereditary cancer risk. The successful implementation of HRR gene testing depends not only on access to sequencing technologies but also on the establishment of a comprehensive pre- and post-analytical framework. The aim of this document is to establish a multidisciplinary expert opinion consensus on the optimisation of molecular assessment of BRCA1/2 and other HRR gene alterations in metastatic prostate cancer to support implementation in clinical practice.