How to cite: Choi S. Evaluating Triplet Therapy in Metastatic Hormone-Sensitive Prostate Cancer. Grand Rounds in Urology. November 13, 2025. Accessed Oct 2026. https://grandroundsinurology.com/evaluating-triplet-therapy-in-metastatic-hormone-sensitive-prostate-cancer/
Summary
Sharon Choi, MD, PhD, Assistant Clinical Professor, Division of Hematology/Oncology, University of California, examines how triplet systemic therapy fits into the evolving treatment landscape for metastatic hormone-sensitive prostate cancer (mHSPC) and highlights the need for careful patient and biomarker selection.
Dr. Choi begins by outlining current options for metastatic hormone-sensitive disease. Doublet therapy combines androgen deprivation therapy (ADT) with an androgen receptor pathway inhibitor (ARPI). Triplet therapy adds docetaxel with agents such as darolutamide or abiraterone. She explains that despite life-prolonging doublet regimens, a significant subset of patients progress and die within a few years, indicating that some clearly need more intensive treatment. She notes the goal of achieving deep, durable remissions that might eventually allow for androgen-free intervals.
Dr. Choi reviews key triplet data. She describes ARASENS, which used ADT and docetaxel as the backbone and randomized patients to receive darolutamide or a placebo. She explains the complex design history of PEACE-1, which evolved as new standards of care emerged, and ultimately used docetaxel as a backbone with randomization to abiraterone and prostate radiation. Because neither ARASENS nor PEACE-1 randomized the docetaxel component, the exact added value of chemotherapy over a doublet remains uncertain. Meta-analyses suggest that any triplet advantage is most pronounced in high-volume disease.
Cooperative group trials are highlighted for their efforts to close this evidence gap. The Alliance ASPIRE study evaluates an ARPI doublet with or without docetaxel. The TRIPLE-SWITCH trial tests adding docetaxel for patients who do not achieve a prostate-specific antigen (PSA) nadir by six to twelve months.
Dr. Choi discusses markers such as SPOP and the Decipher genomic classifier, as well as ongoing and recent triplet trials, including capivasertib-based and radioligand-based strategies. She stresses that future practice should integrate biomarkers, individualized dosing, and long-term safety when considering triplet therapy.
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
Sharon Choi, MD, PhD, is an Assistant Professor of Medicine at the University of California, San Diego, and a medical oncologist with UC San Diego Health. Dr. Choi specializes in the management of urologic malignancies, including prostate, kidney, and bladder cancers. Her practice also focuses on early-phase clinical trials involving treatments such as immunotherapy and targeted therapy for all cancer types.
