Treatment of Metastatic Hormone-Sensitive Prostate Cancer

Background: The landscape of management of metastatic prostate cancer has changed rapidly in the last decade. The emergence of new therapeutics and the increased ability to detect men with metastatic disease still in the hormone-sensitive space has altered the standard of care for advanced prostate cancer. Objective: To describe the biologic basis, evidence, and rationale for use of available treatments for men with metastatic hormone-sensitive prostate cancer (mHSPC). Methods: We performed a narrative, comprehensive review of data for treatment options for patients with mHSPC as of December 1, 2020, with specific emphasis on examining higher-level evidence sources. We reviewed available results of phase II and III randomized controlled trials to assess the indications and efficacy of chemotherapy, local therapy, novel anti-androgen agents (NAA), and metastasis-directed therapy (MDT). Results: Four different agents - docetaxel, abiraterone acetate, enzalutamide, and apalutamide - have data demonstrating improved survival when used in addition to standard androgen deprivation therapy (ADT). No direct comparisons between these agents have been performed, and questions remain regarding optimal sequencing, although overall efficacy appears similar. Numerous trials examining these questions are underway. Toxicity profiles between beneficial agents do differ, however, and will be thoroughly explored in this chapter. Analyses have failed to demonstrate a benefit to local radiotherapy in high-volume metastatic disease. Some data supporting use of radiotherapy in low-volume metastatic disease is emerging. In addition, ongoing prospective trials are assessing if a similar benefit will be seen with surgical treatment. Finally, metastasis-directed therapy appears beneficial among carefully selected patients. Conclusion: Despite many years with few therapeutic advances, treatment options for patients with mHSPC are now evolving rapidly, offering clinicians a number of new agents offering benefit without significant clinical differences between them. Treatment of local disease and metastatic sites with radiation or surgery continues to evolve.