Vinayak Muralidhar1, Ming-Hui Chen2, Gally Reznor3, Brian J Moran4, Michelle H Braccioforte4, Clair J Beard5, Felix Y Feng6, Karen E Hoffman7, Toni K Choueiri8, Neil E Martin5, Christopher J Sweeney8, Quoc-Dien Trinh9, Paul L Nguyen10. 1. Harvard-MIT Division of Health Sciences and Technology, Harvard Medical School, Boston, Massachusetts. 2. Department of Statistics, University of Connecticut, Storrs, Connecticut. 3. Center for Surgery and Public Health, Brigham and Women's Hospital/Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts. 4. Prostate Cancer Foundation of Chicago, Westmont, Illinois. 5. Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Boston, Massachusetts. 6. Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan. 7. Department of Radiation Oncology, M. D. Anderson Cancer Center, Houston, Texas. 8. Department of Medical Oncology, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. 9. Department of Urology, Brigham and Women's Hospital, Boston, Massachusetts. 10. Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Boston, Massachusetts. Electronic address: pnguyen@LROC.harvard.edu.
Abstract
PURPOSE: To define and validate a classification of favorable high-risk prostate cancer that could be used to personalize therapy, given that consensus guidelines recommend similar treatments for all radiation-managed patients with high-risk disease. METHODS AND MATERIALS: We studied 3618 patients with cT1-T3aN0M0 high-risk or unfavorable intermediate-risk prostate adenocarcinoma treated with radiation at a single institution between 1997 and 2013. Favorable high-risk was defined as T1c disease with either Gleason 4 + 4 = 8 and prostate-specific antigen <10 ng/mL or Gleason 6 and prostate-specific antigen >20 ng/mL. Competing risks regression was used to determine differences in the risk of prostate cancer-specific mortality (PCSM) after controlling for baseline factors and treatment. Our results were validated in a cohort of 13,275 patients using the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database. RESULTS: Patients with favorable high-risk disease had significantly better PCSM than other men with high-risk disease (adjusted hazard ratio [AHR] 0.42, 95% confidence interval [CI] 0.18-0.996, P=.049) and similar PCSM as men with unfavorable intermediate-risk disease (AHR 1.17, 95% CI 0.50-2.75, P=.710). We observed very similar results within the SEER-Medicare cohort (favorable high-risk vs other high-risk: AHR 0.21, 95% CI 0.11-0.41, P<.001; favorable high-risk vs unfavorable intermediate-risk: AHR 0.67, 95% CI 0.33-1.36, P=.268). CONCLUSIONS: Patients with favorable high-risk prostate cancer have significantly better PCSM than other patients with high-risk disease and similar PCSM as those with unfavorable intermediate-risk disease, who are typically treated with shorter-course androgen deprivation therapy. This new classification system may allow for personalization of treatment within high-risk disease, such as consideration of shorter-course androgen deprivation therapy for favorable high-risk disease.
PURPOSE: To define and validate a classification of favorable high-risk prostate cancer that could be used to personalize therapy, given that consensus guidelines recommend similar treatments for all radiation-managed patients with high-risk disease. METHODS AND MATERIALS: We studied 3618 patients with cT1-T3aN0M0 high-risk or unfavorable intermediate-risk prostate adenocarcinoma treated with radiation at a single institution between 1997 and 2013. Favorable high-risk was defined as T1c disease with either Gleason 4 + 4 = 8 and prostate-specific antigen <10 ng/mL or Gleason 6 and prostate-specific antigen >20 ng/mL. Competing risks regression was used to determine differences in the risk of prostate cancer-specific mortality (PCSM) after controlling for baseline factors and treatment. Our results were validated in a cohort of 13,275 patients using the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database. RESULTS:Patients with favorable high-risk disease had significantly better PCSM than other men with high-risk disease (adjusted hazard ratio [AHR] 0.42, 95% confidence interval [CI] 0.18-0.996, P=.049) and similar PCSM as men with unfavorable intermediate-risk disease (AHR 1.17, 95% CI 0.50-2.75, P=.710). We observed very similar results within the SEER-Medicare cohort (favorable high-risk vs other high-risk: AHR 0.21, 95% CI 0.11-0.41, P<.001; favorable high-risk vs unfavorable intermediate-risk: AHR 0.67, 95% CI 0.33-1.36, P=.268). CONCLUSIONS:Patients with favorable high-risk prostate cancer have significantly better PCSM than other patients with high-risk disease and similar PCSM as those with unfavorable intermediate-risk disease, who are typically treated with shorter-course androgen deprivation therapy. This new classification system may allow for personalization of treatment within high-risk disease, such as consideration of shorter-course androgen deprivation therapy for favorable high-risk disease.
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