How to cite: Einstein D. Determining the Benefit of Therapy for Biochemically Recurrent Prostate Cancer. Grand Rounds in Urology. September 15, 2025. Accessed Feb 2026. https://grandroundsinurology.com/determining-the-benefit-of-therapy-for-biochemically-recurrent-prostate-cancer/
Summary
David Einstein, MD, Assistant Professor, Harvard Medical School, Boston, Massachusetts, reviews controversies in the management of biochemically recurrent prostate cancer, defined as rising prostate-specific antigen (PSA) after surgery or radiation in the absence of metastatic disease on conventional imaging. He notes that clinicians face the dilemma of when to initiate systemic therapy, balancing disease control with treatment toxicity.
Historical management included immediate androgen deprivation therapy (ADT) or delaying until metastatic progression. Retrospective studies show that even men with rapid PSA doubling times may experience prolonged survival without early therapy, underscoring disease heterogeneity. The advent of prostate-specific membrane antigen positron emission tomography (PSMA PET) complicates definitions by identifying small lesions earlier, creating a new entity: PSA-positive but conventionally negative recurrence.
Dr. Einstein highlights the phase 3 Embark trial, which tested enzalutamide with or without ADT versus ADT alone in high-risk biochemical recurrence. Results showed improved metastasis-free survival with enzalutamide-based regimens, and a press release announced an overall survival benefit, though detailed data are pending. Adverse events led to discontinuation in about 20 percent of patients, emphasizing the trade-offs of early systemic therapy in a largely asymptomatic population.
He introduces the concept of treatment-free survival as a novel endpoint, capturing time off therapy and without toxicity, as a complement to conventional survival outcomes. This patient-centered approach more accurately reflects clinical value in early disease stages.
Dr. Einstein stresses that not all patients with biochemical recurrence require immediate systemic therapy. Decisions should consider prostate-specific antigen kinetics, imaging, and patient factors. Future directions include integrating immunotherapies and radioligand therapies to achieve durable benefit beyond ADT.
The Global Summit on Precision Diagnosis and Treatment of Prostate Cancer is a unique multi-disciplinary forum organized to inform the key health care stakeholders about the emerging advances in clinical cases and research, and create a consensus-based vision for the future of precision care and educational and research strategy for its realization. The mission of the Summit is to fill the currently existing gap between the key experts of in vivo imaging, the world authorities in the in vitro fluid- and tissue-based molecular diagnostics, including genomics, and thought leaders in the development of novel observation strategies (e.g., active surveillance, or AS) and therapeutic interventions.
ABOUT THE AUTHOR
David J. Einstein, MD, is a Genitourinary Medical Oncologist at Beth Israel Deaconess Medical Center (BIDMC) in Boston, Massachusetts. Dr. Einstein also serves as an Assistant Professor of Medicine at Harvard Medical School in Boston. He specializes in cancer of the prostate, bladder, kidney, and testis. Dr. Einstein’s research focuses on immunotherapy and targeted approaches in prostate, bladder, and kidney cancers, with support from the Prostate Cancer Foundation,National Institutes of Health, Department of Defense, BIDMC, and industry partners.
