Metastatic Castration-Resistant Prostate Cancer with BRCA2 Mutation: The Challenge Incorporating PARP Inhibitors and Platinum in Treatment Sequencing

Prostate cancer is the second most frequent malignancy in men worldwide. Despite the improvement in survival achieved by increasingly early diagnosis and advances in treatment, it is still associated with high mortality. Because of its molecular heterogeneity, there is a need to identify genetic alterations in order to apply targeted therapies. Increasing evidence suggests that the PARP inhibitor olaparib could have a significant synthetic lethal effect in prostate cancer with homologous recombination defects, such as BRCA1/2 mutations. It is not yet known if, under these circumstances, platinum-based chemotherapy induces higher response rates in prostate cancer. We present the case of a patient with BRCA2-mutated metastatic castration-resistant prostate cancer whose treatment sequence included carboplatin and olaparib. LEARNING POINTS: Metastatic castration-resistant prostate cancer (mCRPC) remains a lethal disease despite significant progress in treatment. The BRCA2 mutation is associated with worse survival and so timely genetic screening is important. Studies are needed to identify the best therapeutic sequencing strategy for mCRPC harbouring homologous recombination repair defects, which includes PARP inhibitors and platinum.