Navigating the Management of mCSPC From Mono to Quadruple Therapies

E. David Crawford, MD

How to cite: Crawford ED. “Navigating the Management of mCSPC From Mono To Quadruple Therapies.” February, 2026. Accessed Apr 2026. https://grandroundsinurology.com/navigating-the-management-of-mcspc-from-mono-to-quadruple-therapies-2/

Summary

E. David Crawford, MD, Editor-in-Chief of Grand Rounds in Urology and Professor of Urology at the University of California, San Diego, San Diego, California, reviews the evolution of metastatic castration-sensitive prostate cancer (mCSPC) management from androgen deprivation monotherapy to modern doublet, triplet, and emerging quadruple strategies, integrating historical milestones with contemporary randomized trial data.

He begins with a historical overview of androgen deprivation therapy (ADT), including orchiectomy, estrogens, and luteinizing hormone-releasing hormone agonists. Acid phosphatase is considered the first tumor marker in oncology, and the Nobel Prize–recognized work of Huggins and Hodges established endocrine manipulation as an effective systemic therapy. Early randomized comparisons of leuprolide and diethylstilbestrol illustrate the limited size and duration of foundational approval trials.

Dr. Crawford discusses combined androgen blockade, citing the Southwest Oncology Group intergroup study demonstrating a 26% improvement in survival with leuprolide plus flutamide compared with monotherapy. The debate over monotherapy versus doublet therapy persisted for decades despite the survival benefit.

Third-generation androgen receptor signaling inhibitors, including enzalutamide, further expanded treatment options by inhibiting androgen receptor binding, nuclear translocation, and DNA interaction. By 2020, multiple trials established ADT combined with docetaxel or androgen receptor pathway inhibitors (ARPIs) as the standard of care for metastatic hormone-sensitive prostate cancer.

Triplet therapy incorporating ADT, docetaxel, and an ARPI demonstrated additional overall survival gains in high-volume and de novo disease settings. Meta-analyses and cohort analyses reinforce these intensification strategies.

Quadruple therapy extends beyond tumor-directed treatment. Dr. Crawford emphasizes proactive management of cardiovascular, skeletal, and metabolic complications associated with ADT through multidisciplinary coordination. Contemporary management of mCSPC requires both therapeutic intensification and structured mitigation of treatment-related morbidity.

The International Prostate Cancer Update (IPCU), is a multi-day, CME-accredited conference focused on new developments in prostate cancer treatment, diagnosis, and prevention. IPCU 36 will feature lectures, interactive discussions, panel roundtables, debates, and case reports. This conference is led by expert physicians and is designed for urologists, medical oncologists, radiation oncologists, and other healthcare professionals involved in the diagnosis and treatment of prostate cancer.

The goal of this educational program is to equip healthcare professionals involved in the diagnosis and treatment of prostate cancer with the up-to-date clinical knowledge and tools they need to best treat their patients. The program will discuss the treatment of prostate cancer from diagnosis to treating advanced and metastatic disease. The conference aims to give physicians exposure to a comprehensive review of treating prostate cancer patients and to give them a chance to discuss the issues with peers and experts.

ABOUT THE AUTHOR

E. David Crawford, MD

Researcher-physician E. David Crawford, MD, Jack A. Vickers Director of Prostate Research and Professor of Urology at the University of California, San Diego, has devoted his career in medicine to educating the public about men's health issues and finding effective techniques and procedures to address prostate cancer, the most common malignancy affecting men in the United States.

About The Author

E. David Crawford, MD

Researcher-physician E. David Crawford, MD, Jack A. Vickers Director of Prostate Research and Professor of Urology at the University of California, San Diego, has devoted his career in medicine to educating the public about men's health issues and finding effective techniques and procedures to address prostate cancer, the most common malignancy affecting men in the United States. Dr. Crawford received his medical degree from the University of Cincinnati and his postgraduate training included an internship and residency in urology at the Good Samaritan Hospital in Cincinnati. He subsequently completed a genitourinary cancer fellowship at the University of California Medical Center in Los Angeles. Dr. Crawford is an internationally recognized expert in benign prostate hypertrophy, urologic cancers, and in particular, prostate cancer. He has conducted research in the treatment of advanced bladder cancer, metastatic adenocarcinoma of the prostate, hormone-refractory prostate cancer, and other areas of urological infections and malignancies. He has authored or coauthored over 810 scientific articles, has published seven textbooks, authored over 60 book chapters, and provided more than 2,200 educational talks for patients and physicians. In an effort to raise public awareness about prostate health, Crawford in 1989 founded the Prostate Conditions Education Council (PCEC). The non-profit organization is comprised of a consortium of leading physicians, health educators, scientists, and men's health advocates. PCEC's advocacy for free or low-cost prostate screening has affected the lives of millions of American men. He currently chairs the PCEC. Crawford is an active member of many national and international organizations, including the American Society of Clinical Oncology, the American Urological Association (AUA), and the American Association for the Advancement of Science. Within the AUA, he has been a member of the Committee to Study Urologic Research Funding and the prostate cancer clinical trials subcommittee. Crawford served on the board of governors, the scientific advisory board of the Southwest Oncology Group, and was chairman of the Genitourinary Cancer Committee for 27 years. This group is the largest clinical trials group in the world. Crawford's involvement in the national prostate cancer arena has been widely recognized. He has received many honors and awards, including the CAP Cure Annual Award for Scientific Presentation in 1999 In 1997, he was presented with a 'Freddie Award" at the AMA International Health and Medical Film Competition for the program, ITV: The Cutting Edge Medical Report (Prostate Cancer: Understanding, Diagnosing, and Defeating), which Crawford hosted with special guest, retired General Norman Schwarzkopf. Crawford again won a prestigious 'Freddie Award" 5 years ago... He is a member of Best Doctors of America and was named Healthcare Provider of the Year in the Denver Metro area by the Denver Business Journal. He has been recognized as one of the Best Doctors of America for the past two decades and is recognized as one of the top 20 urologists in the country, for men, by Men’s Health Magazine. In 2018 he received the honor of being named the Distinguished Alumnus of the Year from the University of Cincinnati School of Medicine. In May of 2019, he received the Presidential citation from the American Urological Association recognizing for his “tireless role in genitourinary cancer research that has benefited countless urologic cancer patients.” He accepted the position of Editor in Chief of Grand Rounds in Urology in June of 2019. In 2021, he was the recipient of the Merle Stringer, M.D. annual award for excellence in medicine by the Florida State Medical Association.

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