Abstract
The management of metastatic hormone-sensitive prostate cancer (mHSPC) or castration-sensitive prostate cancer (mCSPC) has become increasingly complex with the tremendous progress that has been made in this space within the past few decades. In the early days of androgen deprivation therapy (ADT), ADT monotherapy was the mainstay for treatment of advanced prostate cancer. However, novel hormone therapies in the form of androgen receptor pathway inhibitors (ARPI) have emerged; vaccine therapy, chemotherapy with docetaxel and cabazitaxel, and radioactive ligands have shaped the treatment of metastatic prostate cancer in the last decade. Following the initial approval of several drugs for use in metastatic castration-resistant prostate cancer (mCRPC) in combination with primary ADT, these agents were studied and subsequently approved for use in mCSPC. Therefore, ADT monotherapy no longer constitutes an optimal therapeutic option for otherwise fit patients who present with mCSPC. We focus on the treatment of first-line de novo mHSPC or mCSPC and explore frontline doublet and triplet therapy and the pivotal trials that led to their United States Food and Drug Administration approval.