Abstract
The treatment landscape of metastatic prostate cancer has evolved significantly over the past two decades. Several landmark phase 3 trials led to new drug approvals and rapid changes in therapy options for patients, including drugs with distinct mechanisms of action (e.g., hormonal, chemotherapy, radionuclide, immunotherapy, and targeted therapies). Therapies initially developed in later stages of the disease (metastatic castration resistant prostate cancer) have started to move earlier in the prostate cancer continuum, with new standards of care for metastatic hormone naive prostate cancer and non-metastatic castration resistant prostate cancer. Overall, patients are living longer with a better quality of life. However, despite these significant advances, prostate cancer remains a leading cause of cancer death globally. Disease heterogeneity and the emergence of therapy resistance remain significant barriers, and the identification and application of molecular biomarkers to guide the choice and sequencing of systemic agents are still in early stages. Here we discuss the current treatment landscape of metastatic prostate cancer, clinical challenges, and the emerging role of molecular biomarkers for targeting biologic subsets of advanced disease and co-targeting heterogenous resistance patterns.