How to cite: Yen AE. Treatment de-escalation: strategies to optimize risk/benefit in advanced prostate cancer. September 20, 2025. Accessed December 2025. https://grandroundsinurology.com/treatment-de-escalation-strategies-to-optimize-risk-benefit-in-advanced-prostate-cancer/
Summary
A. Edward Yen, MD, Assistant Professor of Hematology and Oncology, Baylor College of Medicine, Houston, Texas, reviews contemporary evidence on balancing efficacy and toxicity in advanced prostate cancer therapy. He examines the rationale, data, and emerging biomarkers supporting selective treatment de-escalation strategies after years of intensification with chemohormonal and androgen-receptor–targeted approaches.
Dr. Yen shares a representative case of metastatic castration-sensitive prostate cancer (mCSPC) achieving long-term remission on abiraterone and androgen-deprivation therapy (ADT). The scenario highlights a common question: when and in whom can therapy be safely paused?
He reviews the evolution of treatment intensification from ADT monotherapy to the combination and triplet eras, citing pivotal trials including CHAARTED, STAMPEDE, LATITUDE, TITAN, PEACE-1, and ARASENS. While these regimens improve survival, Dr. Yen emphasizes that extended exposure increases cumulative toxicity. Two recent meta-analyses illustrate this trade-off: a JAMA review showing significantly higher risks of cardiovascular events with androgen-receptor pathway inhibitors (ARPIs) and another demonstrating increased rates of fractures and falls.
Transitioning to de-escalation, he revisits SWOG 9346, which compared continuous versus intermittent ADT in mCSPC. Although non-inferiority was not proven, post-hoc analyses suggest that deep prostate-specific antigen (PSA) responses and low-volume disease identify patients more likely to tolerate therapy breaks. Additional prognostic data show improved survival among patients with recurrent or metachronous low-volume disease.
Dr. Yen highlights newer studies refining selective de-escalation, such as ORIOLE, which shows that metastasis-directed stereotactic body radiation therapy (SBRT) can delay systemic therapy, EMBARK, where early intensification with enzalutamide plus ADT enabled longer treatment suspensions, and ArteraAI, the first multimodal predictive biomarker to identify patients benefiting from short-term ADT with radiation.
He notes that optimal care now requires matching disease biology and response depth to treatment duration—using precision tools to reduce toxicity while maintaining oncologic control.
About The 29th Annual Innovations in Urologic Practice:
Presented by co-chairs Mohit Khera, MD, MBA, MPH, and Michael Coburn, MD, FACS, the Innovations in Urologic Practice conference provides a detailed review and commentary on multiple genitourinary and urologic diseases. Among the featured oncological topics are bladder cancer and immunotherapies, as well as upper tract cancer management, prostate cancer, including state-of-the-art imaging, focal therapy, and MRI. Experts also discuss new tools and techniques for nephrectomy and treating advanced renal cell carcinoma. In terms of general urological approaches, the conference also includes pelvic reconstruction and trauma, men’s health topics like male infertility and sexual dysfunction, and ways to diagnose and treat infections in the urology patient.
For further educational activities from this conference, visit our collection page.
ABOUT THE AUTHOR
A. Edward Yen, MD, is an Assistant Professor of Hematology and Oncology at Baylor College of Medicine in Houston, Texas. He is a practicing urologic oncologist at the Bladder Cancer Center in the Dan L. Duncan Comprehensive Cancer Center at Baylor College of Medicine in Houston, Texas. His clinical interests include prostate and genitourinary cancers.
