How to cite: Randall JM. Metastatic Hormone-Sensitive Prostate Cancer (mHSPC): Evaluating Optimal Systemic Treatment Strategies – Doublet. Grand Rounds in Urology. November 13, 2025. Accessed Oct 2026. https://grandroundsinurology.com/metastatic-hormone-sensitive-prostate-cancer-mhspc-evaluating-optimal-systemic-treatment-strategies-doublet/
Summary
J. Michael Randall, MD, Professor of Medicine, University of California, San Diego, San Diego, California, reviews how doublet systemic therapy has transformed the management of metastatic hormone-sensitive prostate cancer (mHSPC). Dr. Randall explains how treatment has progressed from androgen deprivation therapy (ADT) alone to the routine incorporation of additional agents that meaningfully extend survival.
Dr. Randall describes how ADT alone was previously the standard treatment for mHSPC, until several large randomized trials demonstrated that combining ADT with additional therapies improves outcomes. Docetaxel with ADT showed a significant survival benefit, especially in patients with high-volume disease. Abiraterone plus ADT demonstrated a strong survival benefit with a different mechanism of androgen pathway suppression. Side effect considerations include hypertension, hypokalemia, and liver enzyme monitoring. Dr. Randall also reviews novel anti-androgens. Apalutamide, enzalutamide, and later darolutamide all demonstrated significant improvements in outcomes when added to ADT.
Dr. Randall summarizes his clinical decision approach: first, he determines whether patients are fit for chemotherapy and whether the disease burden is high. If so, triplet strategies may be appropriate; otherwise, doublet options may be the better choice. Convenience, comorbidity considerations, lab monitoring needs, pill burden, drug interactions, and patient preferences are other important factors to consider. He also underscores that despite strong evidence, some patients in general practice still receive ADT alone.
Dr. Randall reinforces that doublet therapy represents a major evolution in metastatic hormone-sensitive prostate cancer care and continues to improve patient longevity and treatment personalization.
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.
