In this issue of JAMA Oncology, Shore et al1 present the results of the ENACT randomized phase 2 clinical trial. Between June 2016 and August 2020, 227 men with prostate cancer were randomized with equal probability to either undergo active surveillance alone (AS) or receive treatment with enzalutamide plus AS. The median age at randomization was 65 years, and 53% of patients had low-risk cancer as determined by the National Comprehensive Cancer Network guidelines.2 Patients in the treatment arm were treated with enzalutamide, 160 mg, for 1 year with an initial follow-up for 1 year and a second year of follow-up for remaining patients in the trial. The primary end point was time to pathological or therapeutic prostate cancer progression. Pathological progression in the study was defined as an increase in primary or secondary Gleason pattern by at least 1 or higher proportion of cancer-positive cores (≥15% increase). Therapeutic progression was considered on primary therapy for prostate cancer whether this was prostatectomy, radiation, focal therapy, or any systemic therapy.