Dose-Escalated Radiotherapy Alone or in Combination With Short-Term Androgen Deprivation for Intermediate-Risk Prostate Cancer: Results of a Phase III Multi-Institutional Trial

Author(s): Daniel J. Krauss, MD1; Theodore Karrison, PhD2; Alvaro A. Martinez, MD3; Gerard Morton, MD4; Di Yan, PhD1; Deborah Watkins Bruner, PhD, RN5; Benjamin Movsas, MD6; Mohamed Elshaikh, MD6; Deborah Citrin, MD7; Bruce Hershatter, MD5; Jeff M. Michalski, MD, MBA8; Jason Alexander Efstathiou, MD, PhD9; Adam Currey, MD10; Vivek S. Kavadi, MD11; Fabio L. Cury, MD12; Michael Lock, MD13; Adam Raben, MD14,15; Samantha Andrews Seaward, MD16; Ali El-Gayed, MD17; Joseph P. Rodgers18; and Howard M. Sandler, MD19
Source: DOI: 10.1200/JCO.22.02390 Journal of Clinical Oncology 41, no. 17 (June 10, 2023) 3203-3216.
Anjan J Patel MD

Dr. Anjan Patel's Thoughts

Large phase III study showing short-term ADT + EBRT did not show an improvement in OS compared to EBRT alone. There was an improvement in PSA failure, metastasis rates and prostate cancer-related deaths. If used, SADT+EBRT should be highly individualized, preferably in patients with longer life expectancies and higher SE risk tolerance.


It remains unknown whether or not short-term androgen deprivation (STAD) improves survival among men with intermediate-risk prostate cancer (IRPC) treated with dose-escalated radiotherapy (RT).


The NRG Oncology/Radiation Therapy Oncology Group 0815 study randomly assigned 1,492 patients with stage T2b-T2c, Gleason score 7, or prostate-specific antigen (PSA) value >10 and ≤20 ng/mL to dose-escalated RT alone (arm 1) or with STAD (arm 2). STAD was 6 months of luteinizing hormone–releasing hormone agonist/antagonist therapy plus antiandrogen. RT modalities were external-beam RT alone to 79.2 Gy or external beam (45 Gy) with brachytherapy boost. The primary end point was overall survival (OS). Secondary end points included prostate cancer–specific mortality (PCSM), non-PCSM, distant metastases (DMs), PSA failure, and rates of salvage therapy.


Median follow-up was 6.3 years. Two hundred nineteen deaths occurred, 119 in arm 1 and 100 in arm 2. Five-year OS estimates were 90% versus 91%, respectively (hazard ratio [HR], 0.85; 95% CI, 0.65 to 1.11]; P = .22). STAD resulted in reduced PSA failure (HR, 0.52; P <.001), DM (HR, 0.25; P <.001), PCSM (HR, 0.10; P = .007), and salvage therapy use (HR, 0.62; P = .025). Other-cause deaths were not significantly different (P = .56). Acute grade ≥3 adverse events (AEs) occurred in 2% of patients in arm 1 and in 12% for arm 2 (P <.001). Cumulative incidence of late grade ≥3 AEs was 14% in arm 1 and 15% in arm 2 (P = .29).


STAD did not improve OS rates for men with IRPC treated with dose-escalated RT. Improvements in metastases rates, prostate cancer deaths, and PSA failures should be weighed against the risk of adverse events and the impact of STAD on quality of life.

Author Affiliations

1Corewell Health Beaumont University Hospital, Royal Oak, MI;2NRG Oncology Statistics and Data Management Center, University of Chicago, Chicago, IL;321st Century Oncology of Michigan, Pontiac, MI;4Toronto-Sunnybrook Regional Cancer Center, Toronto, ON, Canada;5Emory University, Atlanta, GA;6Henry Ford Cancer Institute, Detroit, MI;7National Cancer Institute, Bethesda, MD;8Washington University School of Medicine, Saint Louis, MO;9Dana-Farber/Harvard Cancer Center, Boston, MA;10Froedtert and the Medical College of Wisconsin, Milwaukee, WI;11The US Oncology Network, Fairfax, VA;12McGill University Health Center, Montreal, QC, Canada;13London Regional Cancer Program, London, ON, Canada;14Delaware/Christiana Care NCI Community Oncology Research Program, Newark, DE;15Milwaukee Veterans Administration Medical Center, Milwaukee, WI;16Kaiser Permanente NCI Community Oncology Research Program, Oakland, CA;17Saskatoon Cancer Centre, Saskatoon, SK, Canada;18NRG Oncology Statistics and Data Management Center, Philadelphia, PA;19Cedars-Sinai Medical Center, Los Angeles, CA

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