Definitive radiotherapy (RT) for prostate cancer (PC) with dose intensification and/or focal boosting has excellent oncologic outcomes, but many patients experience adverse events. Dose escalation to the whole prostate improves outcomes at the expense of increased late adverse events. Intraprostatic recurrence after definitive RT typically occurs at the site of the primary tumor, suggesting that dose to the site of the dominant lesion is an important predictor of future failure. The efficacy and safety of tumor-focused RT compared to that of standard RT for definitive treatment of localized PC has not been assessed. RadTARGET (RAdiation Dose TAiloRing Guided by Enhanced Targeting) is a phase II randomized trial that aims to demonstrate superior safety of image-guided, tumor-focused RT compared to standard RT for acute genitourinary (GU) or gastrointestinal (GI) in the setting of definitive RT for intermediate- and high-risk PC. The study intervention is image-guided, tumor-focused RT with dose intensification of cancer visible on imaging and dose de-intensification to remaining prostate. Patients will be randomized to two arms: those who receive standard RT dose and those that receive tumor-focused RT. The study population will be patients with intermediate- or high-risk PC planning to undergo definitive RT with or without systemic therapy. The primary endpoint to compare between randomized arms is acute GU or GI grade ≥2 adverse events. Participant and study duration are 5 years and 8 years, respectively. RadTARGET will compare the efficacy and safety of tumor-focused RT to that of standard RT for definitive treatment of localized PC. We hypothesize that the tumor-focused approach will substantially reduce adverse events after prostate RT while retaining high efficacy. If this hypothesis is confirmed, we will conclude that a phase III randomized control trial is warranted to formally establish oncologic non-inferiority compared to the current standard of whole-gland dose escalation.

Dr. Tyler Seibert reports honoraria or consulting fees from Varian Medical Systems, WebMD, MJH Life Sciences, MD Education USA, GE Healthcare, Blue Earth Diagnostics, Janssen, CorTechs Labs, and MyOme. He has stock options in CorTechs Labs, MyOme, and Open Medicine for serving on their scientific advisory boards. He receives research funding and/or in-kind research support from GE Healthcare, Blue Earth Diagnostics, Quibim, AIRA Matrix, Veracyte, and Lantheus, all through the University of California San Diego. These companies might potentially benefit from the research results. The terms of this arrangement have been reviewed and approved by the University of California San Diego in accordance with its conflict-of-interest policies. Dr. Rana McKay serves on the advisory boards of Janssen, Novartis, Tempus, Pfizer, Astellas Medivation, Dendreon, Bayer, Sanofi, Vividion Therapeutics, Calithera Biosciences, Caris Life Sciences, Sorrent Therapeutics, AVEO, Seagen, Telix Pharmaceuticals, Lilly, Blue Earth Diagnostics, Ambrx, Sumitomo Pharma Oncology, Eisai, NeoMorph, Arcus Biosciences, Daiichi Sankyo, Exelixis, Bristol-Myers Squibb, AstraZeneca, Merck, Myovant Sciences and Precede Bio. She also receives research funding from Bayer, Tempus, AstraZeneca, Exelixis, Bristol-Meyers Squibb, Oncternal Therapeutics and Artera. Dr. Michael Liss is the founder of Oncobiomix and receives research funding from MicrogenDx.

NCT06990542

This work was funded by UC San Diego School of Medicine and UC San Diego Moores Cancer Center.

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Ethics committee/IRB of UC San Diego gave ethical approval for this work

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Trial Information ID: NCT06990542, Start Date: June 2025, Sponsor: University of California San Diego, Phase: Phase 2 Prostate Cancer Research Study, Study Type: Interventional

All data produced in the present study are available upon reasonable request to the authors