In this episode of First Assist: GU Oncology Unpacked, host Taylor Goodstein, MD, welcomes back Pretesh Patel, MD, associate professor of radiation oncology at Emory University, for an in-depth discussion on the evolving role of radiation therapy across the spectrum of advanced prostate cancer. Building on their prior conversation about localized disease, Patel focuses on treatment intensification, post-prostatectomy management, and the expanding role of metastasis-directed therapy. The conversation opens with emerging evidence supporting triplet therapy—radiation, androgen deprivation therapy (ADT), and abiraterone acetate (Zytiga)—for very high-risk localized prostate cancer. Patel explains how data from STAMPEDE have influenced practice patterns, leading to closer collaboration with medical oncology and more frequent use of systemic intensification alongside dose-escalated radiation. The discussion then shifts to the post-prostatectomy setting, where recent trials have reshaped the adjuvant vs early salvage radiation debate. Patel outlines how PSA kinetics, imaging, and modern PSMA-PET scanning inform decision-making, while emphasizing that early salvage radiation remains beneficial even when PET imaging is negative. The role of genomic classifiers is explored, particularly in guiding decisions around adding ADT to salvage radiation, though prospective predictive data are still evolving. A significant portion of the episode is dedicated to oligometastatic and oligoprogressive disease. Patel reviews how SBRT is increasingly used to treat limited metastatic lesions, delay systemic therapy, and preserve quality of life. He highlights practical considerations, including patient selection, bone health, fracture risk, and the balance between local control and systemic disease management. The nuances of treating nodal-only recurrence and comprehensive nodal irradiation are also addressed, supported by emerging randomized data. The episode concludes with a forward-looking discussion on innovations shaping radiation oncology, including PSMA-guided treatment planning, AI-driven prognostic tools, and the growing role of radioligand therapy such as lutetium-177 PSMA. Patel emphasizes the importance of multidisciplinary collaboration as imaging, systemic therapies, and radiation techniques continue to converge. This episode offers practical insights for clinicians navigating complex prostate cancer cases and underscores how precision imaging and tailored radiation strategies are redefining care for patients with advanced disease. Chapters 0:38 Triplet therapy for high-risk localized disease 3:48 Salvage vs adjuvant radiation therapy 13:52 Radiating a prostatectomy bed vs radiating a prostate 17:13 PSMA-PET 21:34 Oligometastatic disease 33:12 Bone health

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