How to cite: Polascik TJ. Management of Localized Prostate Cancer: Targeted Therapy. Grand Rounds in Urology. November 2025. Accessed Jan 2026. https://grandroundsinurology.com/management-of-localized-prostate-cancer-targeted-therapy/
Management of Localized Prostate Cancer: Targeted Therapy – Summary
Thomas J. Polascik, MD, FACS, Lawrence C. Katz Distinguished Professor of Urologic Surgery, Duke University, Durham, North Carolina, provides an overview of targeted ablation as an evolving strategy for localized prostate cancer management. He outlines treatment schemas from observation through radical prostatectomy, positioning focal therapy just below active surveillance on the invasiveness scale. Focal ablation can be used in primary, salvage, and repeat settings when new lesions appear.
Dr. Polascik reviews available ablation technologies, including cryotherapy, high-intensity focused ultrasound (HIFU), laser ablation, and newer modalities, emphasizing that success depends on both the precision of energy delivery and the expertise of the operator. Using cryoablation as a model, he explains that the inner ice-ball core produces complete necrosis, while the 2–4 mm rim represents a sublethal zone where cell fate can be influenced. Future strategies aim to sensitize these cells to apoptosis using safe adjuncts such as vitamin D3, which promotes apoptotic signaling without systemic toxicity.
He describes the potential of combinatorial approaches, combining ablation with immunologic stimulation or checkpoint inhibition to amplify systemic T-cell responses. Research into cryo-immunology and immune adjuvants may yield abscopal benefits beyond local control. Dr. Polascik emphasizes the importance of optimizing freeze-thaw cycles, demonstrating that double-freeze or “double-tap” protocols outperform single ablations.
Emerging genomic classifiers predict in-field recurrence and may guide ablation candidacy and follow-up. He cites data showing higher treatment failure rates with elevated genomic scores, suggesting integration of molecular risk assessment into focal therapy planning.
Dr. Polascik envisions an AI-driven future for ablation, incorporating thermal modeling, real-time tumor sensing, and bioresponsive imaging. Techniques such as histotripsy, nanopulse stimulation, and smart laser therapy will enable adaptive control of ablation zones. He predicts that minimally invasive, office-based ablation with robotic or tele-ablation systems will expand access, particularly in underserved settings.
He emphasizes that focal therapy represents a patient-centered, evolving frontier requiring careful selection and long-term monitoring. Integration of imaging, biomarkers, and AI decision support will define its next phase.
ABOUT THE AUTHOR
Thomas J. Polascik, MD, FACS, is the Lawrence C. Katz Distinguished Professor at Duke University Medical Center, where he is Professor of Urology and Radiology, as well as a Member of the Duke Cancer Institute. Dr. Polascik specializes in urology care, including nonsurgical focal cryotherapy for prostate cancer, robotic surgery for prostate cancer, and robotic surgical removal of kidney tumors. Dr. Polasick’s research focuses on prostate cancer imaging, focal therapy of prostate cancer, prostate cancer outcomes, kidney cancer outcomes, minimally invasive surgery, and nerve-sparing cryotherapy for prostate cancer.
