Rapidly evolving treatment paradigm and considerations for sequencing therapies in metastatic prostate cancer—a narrative review

The treatment landscape of metastatic prostate cancer (mPCa) has evolved considerably over the past 15 years with approvals of targeted therapies such as poly-ADP-ribose polymerase inhibitors (PARPi) in castration-resistant [metastatic castration-resistant prostate cancer (mCRPC)] setting and novel antiandrogens and docetaxel in hormone-sensitive [metastatic hormone-sensitive prostate cancer (mHSPC)] setting. A number of promising clinical trials are now evaluating therapeutic combinations rooted in an improving understanding of tumor biology. Despite a plethora of effective treatment options, decisions regarding choice of therapy remain challenging due to the lack of head-to-head trials and a substantial overlap in selection criteria used in these trials. We summarize the data from key trials that led to approval of commonly used mPCa therapies and provides an easy-to-use clinical decision-making framework that incorporates patient-specific and disease-specific factors to aid selection of the optimal therapy. We outline the evolving use-cases for biomarker-guided treatment selection and our approach to incorporating these therapies in clinical practice. Finally, we highlight the rapidly growing pipeline of therapies that are in advanced stages of clinical development, such as combinations of novel antiandrogen and PARPi, vascular endothelial growth factor (VEGF) inhibitor and immunotherapy, as well as prostate specific membrane antigen (PSMA)-targeted therapies, many of which are poised to transform the landscape in the coming decade.