J Clin Oncol 2015 Feb 22;33(4):332-9. Epub 2014 Dec 22.
Thomas M. Pisansky, Mayo Clinic, Rochester, MN; Daniel Hunt and James J. Dignam, Radiation Therapy Oncology Group Statistical Center; Leonard G. Gomella, Thomas Jefferson University, Philadelphia, PA; Mahul B. Amin and Howard M. Sandler, Cedars-Sinai Medical Center, Los Angeles; Daniel M. Chinn, John Muir Medical Center-Concord Campus, Concord; Seth A. Rosenthal, Sutter Medical Group, Sacramento, CA; Michael J. Seider, Akron City Hospital, Akron, OH; Elizabeth M. Gore, Zablocki Veterans Administration Medical Center-Wood, Milwaukee, WI; Marvin Z. Rotman, Brooklyn Minority-Based Community Clinical Oncology Program, State University of New York Downstate, Brooklyn, NY; William U. Shipley, Massachusetts General Hospital, Boston, MA; James J. Dignam, University of Chicago, Chicago, IL; Alexander G. Balogh, Tom Baker Cancer Centre, Calgary, Alberta; Marie Duclos, McGill University, Montreal, Quebec; Glenn S. Bauman, London Regional Cancer Program, London; and Himanshu R. Lukka, McMaster University, Hamilton, Ontario, Canada.
Purpose: To determine whether prolonged androgen suppression (AS) duration before radiotherapy improves survival and disease control in prostate cancer.
Patients And Methods: One thousand five hundred seventy-nine men with intermediate-risk prostate cancer were randomly assigned to 8 weeks of AS followed by radiotherapy with an additional 8 weeks of concurrent AS (16 weeks total) or to 28 weeks of AS followed by radiotherapy with an additional 8 weeks of AS (36 weeks total). The trial sought primarily to detect a 33% reduction in the hazard of prostate cancer death in the 28-week assignment. Time-to-event end points are reported for up to 10 years of follow-up.
Results: There were no between-group differences in baseline characteristics of 1,489 eligible patients with follow-up. For the 8- and 28-week assignments, 10-year disease-specific survival rates were 95% (95% CI, 93.3% to 97.0%) and 96% (95% CI, 94.6% to 98.0%; hazard ratio [HR], 0.81; P = .45), respectively, and 10-year overall survival rates were 66% (95% CI, 62.0% to 69.9%) and 67% (95% CI, 63.0% to 70.8%; HR, 0.95; P = .62), respectively. For the 8- and 28-week assignments, 10-year cumulative incidences of locoregional progression were 6% (95% CI, 4.3% to 8.0%) and 4% (95% CI, 2.5% to 5.7%; HR, 0.65; P = .07), respectively; 10-year distant metastasis cumulative incidences were 6% (95% CI, 4.0% to 7.7%) and 6% (95% CI, 4.0% to 7.6%; HR, 1.07; P = .80), respectively; and 10-year prostate-specific antigen-based recurrence cumulative incidences were 27% (95% CI, 23.1% to 29.8%) and 27% (95% CI, 23.4% to 30.3%; HR, 0.97; P = .77), respectively.
Conclusion: Extending AS duration from 8 weeks to 28 weeks before radiotherapy did not improve outcomes. A lower than expected prostate cancer death rate reduced ability to detect a between-group difference in disease-specific survival. The schedule of 8 weeks of AS before radiotherapy plus 8 weeks of AS during radiotherapy remains a standard of care in intermediate-risk prostate cancer.