Sorting Through the Maze of Treatment Options for Metastatic Castration-Sensitive Prostate Cancer

Since 1944, when Huggins and Hodges demonstrated the effectiveness of bilateral orchiectomy for metastatic prostate cancer (PCa), androgen deprivation therapy (ADT) has been the first-line treatment for men with advanced PCa. The proportion of PCa cases that are metastatic at diagnosis ranges globally, from 5%-20% in countries with widespread screening practices to upward of 30%-60% where screening is minimal. In the United States alone, there will be an estimated 191,000 new cases of PCa diagnosed in the year 2020, of which approximately 20% will be metastatic.¹ Ongoing controversy around prostate-specific antigen (PSA) screening practices, increased access to novel imaging modalities, and a globally aging population will drive increased rates of metastatic castration-sensitive prostate cancer (mCSPC).^2,3 At the same time, advances in upfront hormonal or chemohormonal therapy have driven a dramatic shift in treatment paradigms. In this article, we review recent advances in treatment choices for men with newly diagnosed mCSPC and the impact of upfront treatment on subsequent disease biology. Options include treatment with chemohormonal therapy, androgen receptor (AR)-directed therapy in addition to ADT, or, less commonly, ADT alone. Treatment choice must include consideration of clinical and disease characteristics, as well as patient preferences and limitations of geography and financial concerns.