How to cite: Randall JM. “Biochemical Recurrence (BCR) Treatment: Comparing Targeted Approaches for Rising PSA, ADT + Enzalutamide.” Grand Rounds in Urology. November 13, 2025. Accessed Oct 2026. https://grandroundsinurology.com/biochemical-recurrence-bcr-treatment-comparing-targeted-approaches-for-rising-psa-adt-enzalutamide/
Summary
J. Michael Randall, MD, Professor of Medicine, University of California, San Diego, San Diego, California, compares targeted approaches to the management of high-risk biochemical recurrence in prostate cancer, specifically androgen deprivation therapy (ADT) plus enzalutamide versus ADT alone versus enzalutamide monotherapy. Dr. Randall explains that many men with high-risk features eventually experience biochemical recurrence and describes historical uncertainty about standardized management. He notes that prostate-specific antigen (PSA) doubling time is critical, since shorter doubling times are associated with a higher risk of disease progression and metastasis, and explains that past practice often relied on intermittent ADT without strong phase 3 trial guidance.
Dr. Randall reviews the results of the EMBARK trial, which enrolled patients with specific PSA criteria and a rapid PSA doubling time, and randomized them into three arms: ADT plus enzalutamide, ADT plus placebo, and enzalutamide monotherapy. The primary endpoint of the trial was metastasis-free survival, with a treatment stop point at approximately nine months for men achieving very low PSA.
Dr. Randall describes how both the combination therapy and monotherapy arms demonstrated superiority over ADT alone for the primary endpoint in earlier reporting, noting that more recent follow-up focuses on overall survival. This data illustrates that ADT plus enzalutamide demonstrates a meaningful overall survival advantage over enzalutamide monotherapy or ADT alone.
Reviewing adverse event patterns, including differences in hot flashes, fatigue, and breast-related symptoms, Dr. Randall emphasizes the relevance of side effect tolerance when counseling patients on treatment decisions. He reasserts that ADT plus enzalutamide is the preferred option for patients with high-risk biochemical recurrence, while monotherapy remains appropriate for selected patients who cannot or will not receive ADT.
About the 32nd Annual Perspectives in Urology: Point Counterpoint conference: Presented by Program Chair and Grand Rounds in Urology Editor-in-Chief E. David Crawford, MD, this conference brought together leading experts in urology, medical oncology, and radiation oncology to discuss and debate the latest topics in genitourinary cancers, primarily prostate cancer and bladder cancer. This interactive conference offered topical lectures, pro/con debates, interesting-case presentations, interactive panel discussions, and interactive audience and faculty networking.
ABOUT THE AUTHOR
J. Michael Randall, MD, is a Professor of Medicine at the University of California, San Diego. Dr. Randall specializes in treating patients with urologic cancer. He is part of the University of California’s multidisciplinary urologic cancer team, working with urologists and radiation oncologists to care for patients with kidney, prostate, and bladder cancer.
