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
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
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).
To test in a prospective, randomized trial the hypothesis that the addition of 6 months of androgen deprivation will provide a survival advantage for men with intermediate-risk prostate cancer (IRPC) when added to dose-escalated radiation therapy.
Although 6 months of androgen deprivation did not produce an overall survival (OS) advantage, it was associated with improvements in rates of biochemical failure, distant metastases (DMs), and prostate cancer–specific mortality. Although no patient subgroups showed an OS advantage, nearly all had reduced rates of DMs and prostate-specific antigen failure with androgen deprivation added. Adverse event rates were significantly higher in patients receiving androgen deprivation and must be weighed against its anticipated clinical benefits.
Relevance (M.A. Carducci)
This long-awaited report sheds light on the potential clinical benefits of short-term androgen-deprivation therapy for IRPC. Along with the accompanying report on patient-reported outcomes, these results allow the clinician and patient to determine the risk/benefits of STAD in this patient population.*
*Relevance section written by JCO Associate Editor Michael A. Carducci, MD, FACP, FASCO.
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Presented at ASTRO 2021, Chicago, IL, October 24-27, 2021.
This trial was supported by the following grants from the National Cancer Institute: UG1CA189867 to the NCI Community Oncology Research Program; U10CA180868 to NRG Oncology operations; U24CA180803 to the Imaging and Radiation Oncology Core (IROC); and U10CA180822 to the Statistical and Data Management Center.
NCT00936390 (RTOG 0815)
According to National Cancer Institute (NCI) requirements, the data from this article will be submitted to the NCI National Clinical Trials Network (NCTN), NCI Community Oncology Research Program (NCORP) data archive (https://nctn-data-archive.nci.nih.gov) no later than 6 months after publication. After the required NCI reviews are completed, it will be released and available in the data archive for data-sharing proposals. The study protocol is available on the ClinicalTrials.gov website.
Conception and design: Daniel J. Krauss, Alvaro A. Martinez, Gerard Morton, Di Yan, Deborah Watkins Bruner, Mohamed Elshaikh, Deborah Citrin, Jeff M. Michalski, Howard M. Sandler
Administrative support: Jeff M. Michalski
Provision of study materials or patients: Gerard Morton, Di Yan, Bruce Hershatter, Jeff M. Michalski, Jason Alexander Efstathiou, Vivek S. Kavadi, Fabio L. Cury, Michael Lock, Adam Raben, Samantha Andrews Seaward, Ali El-Gayed
Collection and assembly of data: Daniel J. Krauss, Gerard Morton, Di Yan, Deborah Watkins Bruner, Deborah Citrin, Bruce Hershatter, Adam Currey, Fabio L. Cury, Michael Lock, Adam Raben, Samantha Andrews Seaward, Ali El-Gayed, Joseph P. Rodgers
Data analysis and interpretation: Daniel J. Krauss, Theodore Karrison, Alvaro A. Martinez, Gerard Morton, Benjamin Movsas, Deborah Citrin, Jeff M. Michalski, Jason Alexander Efstathiou, Adam Currey, Vivek S. Kavadi, Fabio L. Cury, Michael Lock, Adam Raben, Joseph P. Rodgers
Manuscript writing: All authors
Final approval of manuscript: All authors
Accountable for all aspects of the work: All authors
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Employment: Odette Cancer Centre—Sunnybrook Hospital
Deborah Watkins Bruner
Employment: Emory University
Stock and Other Ownership Interests: AbbVie, Altria, Bristol Myers Squibb, GlaxoSmithKline, Johnson & Johnson, Pfizer, Procter & Gamble, Stryker, Viatris, Walgreens Boots Alliance
Honoraria: American Society of Radiation Oncology (ASTRO), Oncology Nursing Society, Memorial Sloan-Kettering Cancer Center, Alliance, Wilmont Cancer Center
Consulting or Advisory Role: Flatiron Health, Alliance for Clinical Trials in Oncology, University of Rochester
Research Funding: Varian Medical Systems (Inst), Philips Healthcare (Inst), ViewRay (Inst)
Patents, Royalties, Other Intellectual Property: Lung phantom for image guidance, MR-CT imaging-related patent for radiation oncology
Travel, Accommodations, Expenses: Varian Medical Systems, viewray, Alpha Tau
Employment: Mid-Atlantic Permanente Medical Group
Jeff M. Michalski
Stock and Other Ownership Interests: ViewRay
Consulting or Advisory Role: Mevion Medical Systems, Boston Scientific, Merck Sharp & Dohme, Blue Earth Diagnostics
Research Funding: Merck Sharp & Dohme (Inst)
Travel, Accommodations, Expenses: Boston Scientific, Merck Sharp & Dohme
Open Payments Link: https://openpaymentsdata.cms.gov/physician/221723
Jason Alexander Efstathiou
Consulting or Advisory Role: Blue Earth Diagnostics, AstraZeneca, Boston Scientific, Merck, Janssen, Genentech, Bayer, Progenics, Pfizer, Gilead Sciences, Myovant Sciences, Lantheus Medical Imaging, Blue Earth Diagnostics
Vivek S. Kavadi
Employment: US Oncology Network
Stock and Other Ownership Interests: McKesson/US Oncology Network
Fabio L. Cury
Consulting or Advisory Role: Knight Pharmaceuticals, Sanofi/Aventis
Speakers' Bureau: Varian Medical Systems
Research Funding: Boston Scientific (Inst), Tolmar (Inst)
Travel, Accommodations, Expenses: Varian Medical Systems
Stock and Other Ownership Interests: Myovant Sciences
Consulting or Advisory Role: Sanofi, Tersera
Speakers' Bureau: Ferring, AbbVie, Eisai
Honoraria: Bristol Myers Squibb
Speakers' Bureau: Bristol Myers Squibb
Travel, Accommodations, Expenses: Bristol Myers Squibb
Howard M. Sandler
Consulting or Advisory Role: Janssen
Other Relationship: Caribou Publishing
No other potential conflicts of interest were reported.