DNA repair gene alterations testing in prostate cancer: A practical update by the prostate cancer committee of the french association of urology

Abstract

Current therapeutic developments in prostate cancer (PCa) tend to increasingly personalize the treatment strategy, in particular as a function of tumor genomics. Recently, poly ADP-ribose polymerase (PARPi) inhibitors have shown their efficacy at the stage of castration resistance, in case of alteration of DNA repair genes in tumor tissue. A narrative review was carried out on recent data in the literature since 2000. A consensus among the members of the Committee was obtained in order to synthesize the current data, with a particular focus on the practical considerations regarding indications and developments of molecular testing circuits concerning DNA repair genes, for theranostics purpose. The establishment of an efficient molecular testing network is based on the multidisciplinary organization of the various actors and the coordination of all material resources. Its goal is the routine search for somatic mutations (in tumor tissue) of BRCA1/2 genes in patients who may benefit from PARPi. The current indications are for BRCA1 or 2 mutated castration-resistant metastatic PCa after next-generation hormone therapy failure. The demand for molecular testing must be decided in the tumor board, giving priority to archived tissue less than 10 years old. In case of unsuccess, biopsies of the primary or metastases, or even analysis of circulating tumor DNA, may be necessary. Any demand for a genetic test on tumor tissue must be accompanied by detailed information for the patient on the possible familial consequences, in case of associated germline mutation. This article aims to guide the practical implementation of molecular testing circuits for DNA repair genes alterations, in order to guide the therapeutic management of patients with advanced PCa.