There has previously been no approved treatment for nonmetastatic castration-resistant prostate cancer (nmCRPC), due to a lack of evidence that any drug would prevent disease progression in this population; now this may change. Here, Neal Shore, MD, FACS, of Carolina Urologic Research Center, Myrtle Beach, SC, discusses the Phase III randomized, prospective PROSPER trial (NCT02003924) of enzalutamide for nmCRPRC. Dr Shore discusses the rationale, aims, design and results of the trial, as well as the approved indications and evidence for the use of enzalutamide. This video was recorded at the 2018 Genitourinary Cancers Symposium, held in San Francisco, CA.