Emerging Subtypes and New Treatments for Castration-Resistant Prostate Cancer

Genomic characterization of metastatic castration-resistant prostate cancer (mCRPC) has been remodeling the treatment landscape of this disease in the past decade. The emergence of molecularly defined subsets of mCRPC is altering the treatment paradigm from therapeutics with nonspecific activity across the spectrum, including androgen receptor (AR)-directed treatments, docetaxel, and cabazitaxel, to targeted approaches directed at molecular subsets of disease. The meaningful benefit of PARP inhibitors in mCRPC carrying mutations in DNA repair genes demonstrated in a phase III trial epitomizes this transition in the treatment paradigm of mCRPC and brings new challenges related to how to sequence and integrate the targeted therapies on top of the treatments with broad activity in all mCRPC. To enable and sustain the advance of precision oncology in the management of mCRPC, genomic characterization is required, including somatic and germline testing, for all patients with the ultimate goal of longitudinal molecular profiling guiding treatment decisions and sequential treatments of this lethal disease. This article reviews the emerging molecular subtypes of mCRPC that are driving the evolution of mCRPC treatment.