Abstract Purpose: This study evaluated the clinical outcomes and toxicity of hypo-fractionated prostate radiotherapy combined with elective pelvic nodal irradiation and androgen deprivation therapy (ADT) in patients with unfavorable intermediate-risk, high-risk, and very high-risk localized prostate cancer. Methods: A retrospective analysis was conducted on 152 consecutively treated patients from 2014 to 2024. After excluding 21 deaths unrelated to prostate cancer, 131 patients formed the study cohort. All patients received volumetric modulated arc therapy (VMAT) with daily cone-beam CT image guidance. Treatment consisted of prostate hypo-fractionation delivered with a simultaneous integrated boost and pelvic nodal irradiation to 46-50 Gy in 20-25 fractions. ADT was administered for 6-24 months according to disease risk. Patients were followed for biochemical relapse-free survival (bRFS), disease-free survival (DFS), overall survival (OS), and genitourinary (GU) and gastrointestinal (GI) toxicity. Results: With a median follow-up of 55 months, the cohort demonstrated a DFS rate of 93.8% and an OS rate of 97.7%. Eight patients experienced progression, including five metastatic deaths and three biochemical failures. Cumulative grade III or higher GU toxicity was 3.8%, including one grade IV event; no grade III or higher GI toxicity occurred. Toxicity remained low despite pelvic treatment, likely attributable to modern VMAT planning, daily image guidance, and consistent bowel and bladder preparation. Conclusions: Hypo-fractionated prostate radiotherapy with elective pelvic nodal coverage and ADT produced excellent long-term disease control with minimal severe toxicity in high-risk and very high-risk prostate cancer. These findings support the safety and effectiveness of elective pelvic nodal irradiation when delivered with contemporary image-guided radiotherapy techniques and reinforce its potential role in the modern management of high-risk disease. Citation Format: Eashwer Reddy, Affan Ahmad Ansari, Inamul Haque, Dunia Khaled, John Park. Hypofractionated prostate and pelvic nodal radiotherapy with androgen deprivation therapy for high-risk prostate cancer: A retrospective analysis of oncologic outcomes and toxicity abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 7369.
Reddy et al. (Fri,) studied this question.