Radiation dose tailoring guided by enhanced targeting (RadTARGET): A multi-center randomized controlled trial.

Abstract

TPS409 Background: Definitive radiation therapy for localized prostate cancer with dose intensification and/or focal boosting has excellent oncologic outcomes. However, many patients experience long-term toxicity. Given the long-term survivorship after definitive prostate cancer treatment, there is interest in identifying strategies that can improve the therapeutic ratio of definitive radiation therapy by minimizing toxicity while maintaining excellent oncologic outcomes. Patterns of failure analyses demonstrate that intraprostatic recurrence after definitive radiation therapy occurs nearly always at the site of the primary tumor and that dose to the site of the primary tumor is an important predictor of future failure. Advanced MRI and PSMA PET/CT permit accurate discrimination of tumor from benign prostatic tissue, allowing for the possibility of concentrating radiation dose to the tumor while de-escalating dose to the uninvolved prostate gland. This strategy also lowers the dose to neighboring organs (i.e. rectum, bladder), potentially reducing rates of acute and late adverse events and minimizing the impact of prostate cancer treatment on quality of life. A randomized trial is required to compare the efficacy and toxicity of tumor-focused radiation therapy to that of standard radiation therapy for definitive treatment of localized prostate cancer. Methods: The RadTARGET trial (NCT06990542) is an investigator-initiated, multi-center, prospective, single-blind, pragmatic, two-arm randomized phase II study where patients with intermediate- or high-risk localized prostate cancer planning to undergo definitive radiation therapy with curative intent are randomized to either standard dose radiotherapy or image-guided tumor-focused radiotherapy. Patients with biopsy-proven intermediate- or high-risk localized prostate cancer with lesion visible on prostate MRI and/or PSMA PET/CT (with concordant pathology from biopsy needle locations) are eligible. This trial aims to include 150 patients randomized to one of the two arms in a 1:1 ratio via dynamic allocation to balance risk group, fractionation, intended duration of androgen deprivation therapy, bladder filling protocol, and intended spacer use. The primary endpoint is physician-reported acute any attribution genitourinary (GU) or gastrointestinal (GI) grade ≥2 toxicity within 3 months post-radiation therapy. Key secondary endpoints are radiation attribution acute GU/GI toxicity, any and radiation attribution late GU/GI toxicity, patient-reported urinary and bowel quality of life, biochemical recurrence-free survival, local failure rate, regional and/or distant metastasis-free survival (dMFS), and overall survival. RadTARGET has enrolled approximately 10% of planned patients. Clinical trial information: NCT06990542 .