Christopher U Jones1, Stephanie L Pugh2, Howard M Sandler3, Michael P Chetner4, Mahul B Amin5, Deborah W Bruner6, Anthony L Zietman7, Robert B Den8, Mark H Leibenhaut9, John M Longo10, Jean-Paul Bahary11, Seth A Rosenthal9, Luis Souhami12, Jeff M Michalski13, Alan C Hartford14, Pradip P Amin15, Mack Roach16, Don Yee17, Jason A Efstathiou7, Joseph P Rodgers2, Felix Y Feng16, William U Shipley7. 1. Sutter Medical Center Sacramento, Roseville, California. Electronic address: jonescu@sutterhealth.org. 2. NRG Oncology Statistics and Data Management Center, Philadelphia, Pennsylvania. 3. Cedars-Sinai Medical Center, Los Angeles, California. 4. University of Alberta, Edmonton, Alberta, Canada. 5. University of Tennessee Health Science Center, Memphis, Tennessee. 6. Emory University, Atlanta, Georgia. 7. Massachusetts General Hospital Cancer Center, Boston, Massachusetts. 8. Thomas Jefferson University Hospital, Philadelphia, Pennsylvania. 9. Sutter Medical Center Sacramento, Roseville, California. 10. Froedtert and the Medical College of Wisconsin, Milwaukee, Wisconsin. 11. Centre Hospitalier De L`Université De Montréal-Notre Dame, Montréal, Quebec, Canada. 12. The Research Institute of the McGill University Health Centre, Montréal, Quebec, Canada. 13. Washington University School of Medicine, St. Louis, Missouri. 14. Dartmouth Hitchcock Medical Center, Lebanon, New Hampshire. 15. University of Maryland/Greenebaum Cancer Center, Baltimore, Maryland. 16. UCSF Medical Center-Mount Zion, San Francisco, California. 17. Cross Cancer Institute, Edmonton, Alberta, Canada.
Abstract
PURPOSE: For men with localized prostate cancer, NRG Oncology/Radiation Therapy Oncology Group (RTOG) 9408 demonstrated that adding short-term androgen deprivation therapy (ADT) to radiation therapy (RT) improved the primary endpoint of overall survival (OS) and improved disease-specific mortality (DSM), biochemical failure (BF), local progression, and freedom from distant metastases (DM). This study was performed to determine whether the short-term ADT continued to improve OS, DSM, BF, and freedom from DM with longer follow-up. METHODS AND MATERIALS: From 1994 to 2001, NRG/RTOG 9408 randomized 2028 men from 212 North American institutions with T1b-T2b, N0 prostate adenocarcinoma and prostate-specific antigen (PSA) ≤20ng/mL to RT alone or RT plus short-term ADT. Patients were stratified by PSA, tumor grade, and surgical versus clinical nodal staging. ADT was flutamide with either goserelin or leuprolide for 4 months. Prostate RT (66.6 Gy) was started after 2 months. OS was calculated at the date of death from any cause or at last follow-up. Secondary endpoints were DSM, BF, local progression, and DM. Acute and late toxic effects were assessed using RTOG toxicity scales. RESULTS: Median follow-up in surviving patients was 14.8 years (range, 0.16-21.98). The 10-year and 18-year OS was 56% and 23%, respectively, with RT alone versus 63% and 23% with combined therapy (HR 0.94; 95% confidence interval [CI], 0.85-1.05; P = .94). The hazards were not proportional (P = .003). Estimated restricted mean survival time at 18 years was 11.8 years (95% CI, 11.4-12.1) with combined therapy versus 11.3 years with RT alone (95% CI, 10.9-11.6; P = .05). The 10-year and 18-year DSM was 7% and 14%, respectively, with RT alone versus 3% and 8% with combined therapy (HR 0.56; 95% CI, 0.41-0.75; P < .01). DM and BF favored combined therapy at 18 years. Rates of late grade ≥3 hepatic, gastrointestinal, and genitourinary toxicity were ≤1%, 3%, and 8%, respectively, with combined therapy versus ≤1%, 2%, and 5% with RT alone. CONCLUSIONS: Further follow-up demonstrates that OS converges at approximately 15 years, by which point the administration of 4 months of ADT had conferred an estimated additional 6 months of life.
PURPOSE: For men with localized prostate cancer, NRG Oncology/Radiation Therapy Oncology Group (RTOG) 9408 demonstrated that adding short-term androgen deprivation therapy (ADT) to radiation therapy (RT) improved the primary endpoint of overall survival (OS) and improved disease-specific mortality (DSM), biochemical failure (BF), local progression, and freedom from distant metastases (DM). This study was performed to determine whether the short-term ADT continued to improve OS, DSM, BF, and freedom from DM with longer follow-up. METHODS AND MATERIALS: From 1994 to 2001, NRG/RTOG 9408 randomized 2028 men from 212 North American institutions with T1b-T2b, N0 prostate adenocarcinoma and prostate-specific antigen (PSA) ≤20ng/mL to RT alone or RT plus short-term ADT. Patients were stratified by PSA, tumor grade, and surgical versus clinical nodal staging. ADT was flutamide with either goserelin or leuprolide for 4 months. Prostate RT (66.6 Gy) was started after 2 months. OS was calculated at the date of death from any cause or at last follow-up. Secondary endpoints were DSM, BF, local progression, and DM. Acute and late toxic effects were assessed using RTOG toxicity scales. RESULTS: Median follow-up in surviving patients was 14.8 years (range, 0.16-21.98). The 10-year and 18-year OS was 56% and 23%, respectively, with RT alone versus 63% and 23% with combined therapy (HR 0.94; 95% confidence interval [CI], 0.85-1.05; P = .94). The hazards were not proportional (P = .003). Estimated restricted mean survival time at 18 years was 11.8 years (95% CI, 11.4-12.1) with combined therapy versus 11.3 years with RT alone (95% CI, 10.9-11.6; P = .05). The 10-year and 18-year DSM was 7% and 14%, respectively, with RT alone versus 3% and 8% with combined therapy (HR 0.56; 95% CI, 0.41-0.75; P < .01). DM and BF favored combined therapy at 18 years. Rates of late grade ≥3 hepatic, gastrointestinal, and genitourinary toxicity were ≤1%, 3%, and 8%, respectively, with combined therapy versus ≤1%, 2%, and 5% with RT alone. CONCLUSIONS: Further follow-up demonstrates that OS converges at approximately 15 years, by which point the administration of 4 months of ADT had conferred an estimated additional 6 months of life.
Authors: Mack Roach; Gerald Hanks; Howard Thames; Paul Schellhammer; William U Shipley; Gerald H Sokol; Howard Sandler Journal: Int J Radiat Oncol Biol Phys Date: 2006-07-15 Impact factor: 7.038
Authors: Miljenko V Pilepich; Kathryn Winter; Colleen A Lawton; Robert E Krisch; Harvey B Wolkov; Benjamin Movsas; Eugen B Hug; Sucha O Asbell; David Grignon Journal: Int J Radiat Oncol Biol Phys Date: 2005-04-01 Impact factor: 7.038
Authors: M Bolla; D Gonzalez; P Warde; J B Dubois; R O Mirimanoff; G Storme; J Bernier; A Kuten; C Sternberg; T Gil; L Collette; M Pierart Journal: N Engl J Med Date: 1997-07-31 Impact factor: 91.245
Authors: James J Dignam; Daniel A Hamstra; Herbert Lepor; David Grignon; Harmar Brereton; Adam Currey; Seth Rosenthal; Kenneth L Zeitzer; Varagur M Venkatesan; Eric M Horwitz; Thomas M Pisansky; Howard M Sandler Journal: J Clin Oncol Date: 2018-12-07 Impact factor: 44.544
Authors: Michel Bolla; Theodorus M de Reijke; Geertjan Van Tienhoven; Alphonsus C M Van den Bergh; Jorg Oddens; Philip M P Poortmans; Eliahu Gez; Paul Kil; Atif Akdas; Guy Soete; Oleg Kariakine; Elsbietha M van der Steen-Banasik; Elena Musat; Marianne Piérart; Murielle E Mauer; Laurence Collette Journal: N Engl J Med Date: 2009-06-11 Impact factor: 91.245
Authors: Abrahim Al-Mamgani; Wim L J van Putten; Wilma D Heemsbergen; Geert J L H van Leenders; Annerie Slot; Michel F H Dielwart; Luca Incrocci; Joos V Lebesque Journal: Int J Radiat Oncol Biol Phys Date: 2008-05-19 Impact factor: 7.038
Authors: David P Dearnaley; Matthew R Sydes; John D Graham; Edwin G Aird; David Bottomley; Richard A Cowan; Robert A Huddart; Chakiath C Jose; John Hl Matthews; Jeremy Millar; A Rollo Moore; Rachel C Morgan; J Martin Russell; Christopher D Scrase; Richard J Stephens; Isabel Syndikus; Mahesh K B Parmar Journal: Lancet Oncol Date: 2007-06 Impact factor: 41.316