Jesse D Sammon1, Firas Abdollah1, Gally Reznor2, Daniel Pucheril1, Toni K Choueiri3, Jim C Hu4, Simon P Kim5, Marianne Schmid2, Akshay Sood1, Maxine Sun6, Adam S Kibel2, Paul L Nguyen7, Mani Menon1, Quoc-Dien Trinh8. 1. VUI Center for Outcomes Research Analytics and Evaluation, Henry Ford Health System, Detroit, MI, USA. 2. Division of Urologic Surgery and Center for Surgery and Public Health, Brigham and Women's Hospital / Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA. 3. Department of Medical Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. 4. Department of Urology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA. 5. Department of Urology, Yale University, New Haven, CT, USA. 6. Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Center, Montreal, Canada. 7. Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. 8. Division of Urologic Surgery and Center for Surgery and Public Health, Brigham and Women's Hospital / Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA. Electronic address: qtrinh@partners.org.
Abstract
BACKGROUND: Primary androgen deprivation therapy (pADT) is commonly used to treat elderly men diagnosed with localized prostate cancer (CaP), despite the lack of evidence supporting its use. OBJECTIVE: To examine the effect of pADT on mortality and to assess contemporary trends of pADT use in elderly men with CaP. DESIGN, SETTING, AND PARTICIPANTS: Men older than 65 yr residing in Surveillance, Epidemiology, and End Results (SEER) registry areas diagnosed with localized or locally advanced CaP between 1992 and 2009 and not receiving definitive therapy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Propensity score (PS)-weighted Cox proportional hazards models were used to estimate the effect of pADT use on overall survival among patients receiving pADT. The interaction between comorbidity-adjusted life expectancy (LE) and pADT use was assessed within the Cox and PS-weighted models. Contemporary (2004-2009) trends for pADT use were analyzed by linear regression. RESULTS AND LIMITATIONS: The primary cohort included 46 376 men, of whom 17 873 received pADT (39%). Patients with >10 yr LE had lower pADT utilization rates than patients with short LE. Between 2004 and 2009, the use of pADT in men with localized CaP decreased by 14% (from 36% to 22%). Relative to observation, pADT was associated with a survival disadvantage, with a hazard ratio for all-cause mortality of 1.37 (95% confidence interval 1.20-1.56). Limitations included biases not accounted for by the PS-weighted model, changes in CaP staging over the study period, the absence of prostate-specific antigen (PSA) data prior to 2004, and the limits of retrospective analysis to demonstrate causality. CONCLUSIONS: The use of pADT in elderly men with localized CaP has decreased over time. For men forgoing primary definitive therapy, the use of pADT is not associated with a survival benefit compared to observation, and denies men an opportunity for cure with definitive therapy. The deleterious effect of pADT is most pronounced in men with prolonged LE. PATIENT SUMMARY: In this report, we assessed the effect of primary androgen deprivation (pADT) on prostate cancer mortality and determined current trends in the use of pADT. We showed that use of pADT in men aged >65 yr with localized prostate cancer has decreased over time. We also found that pADT is detrimental to men with localized prostate cancer, and particularly men with longer life expectancy. Therefore, we conclude that ADT should not be used as a primary treatment for men with prostate cancer that has not spread beyond the prostate.
BACKGROUND: Primary androgen deprivation therapy (pADT) is commonly used to treat elderly men diagnosed with localized prostate cancer (CaP), despite the lack of evidence supporting its use. OBJECTIVE: To examine the effect of pADT on mortality and to assess contemporary trends of pADT use in elderly men with CaP. DESIGN, SETTING, AND PARTICIPANTS: Men older than 65 yr residing in Surveillance, Epidemiology, and End Results (SEER) registry areas diagnosed with localized or locally advanced CaP between 1992 and 2009 and not receiving definitive therapy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Propensity score (PS)-weighted Cox proportional hazards models were used to estimate the effect of pADT use on overall survival among patients receiving pADT. The interaction between comorbidity-adjusted life expectancy (LE) and pADT use was assessed within the Cox and PS-weighted models. Contemporary (2004-2009) trends for pADT use were analyzed by linear regression. RESULTS AND LIMITATIONS: The primary cohort included 46 376 men, of whom 17 873 received pADT (39%). Patients with >10 yr LE had lower pADT utilization rates than patients with short LE. Between 2004 and 2009, the use of pADT in men with localized CaP decreased by 14% (from 36% to 22%). Relative to observation, pADT was associated with a survival disadvantage, with a hazard ratio for all-cause mortality of 1.37 (95% confidence interval 1.20-1.56). Limitations included biases not accounted for by the PS-weighted model, changes in CaP staging over the study period, the absence of prostate-specific antigen (PSA) data prior to 2004, and the limits of retrospective analysis to demonstrate causality. CONCLUSIONS: The use of pADT in elderly men with localized CaP has decreased over time. For men forgoing primary definitive therapy, the use of pADT is not associated with a survival benefit compared to observation, and denies men an opportunity for cure with definitive therapy. The deleterious effect of pADT is most pronounced in men with prolonged LE. PATIENT SUMMARY: In this report, we assessed the effect of primary androgen deprivation (pADT) on prostate cancer mortality and determined current trends in the use of pADT. We showed that use of pADT in men aged >65 yr with localized prostate cancer has decreased over time. We also found that pADT is detrimental to men with localized prostate cancer, and particularly men with longer life expectancy. Therefore, we conclude that ADT should not be used as a primary treatment for men with prostate cancer that has not spread beyond the prostate.
Authors: Shrujal S Baxi; Minal Kale; Salomeh Keyhani; Benjamin R Roman; Annie Yang; Antonio P Derosa; Deborah Korenstein Journal: Med Care Date: 2017-07 Impact factor: 2.983
Authors: Ted A Skolarus; Megan Ev Caram; Christina H Chapman; David C Smith; Brent K Hollenbeck; Sarah Hawley; Alexander Tsodikov; Anne Sales; Daniela Wittmann; Alexander Zaslavsky Journal: Cancer Date: 2018-09-07 Impact factor: 6.860
Authors: Paolo Dell'oglio; Anne Sophie Valiquette; Sami-Ramzi Leyh-Bannurah; Zhe Tian; Vincent Trudeau; Alessandro Larcher; Shahrokh F Shariat; Umberto Capitanio; Alberto Briganti; Markus Graefen; Francesco Montorsi; Pierre I Karakiewicz Journal: Can Urol Assoc J Date: 2018-03-19 Impact factor: 1.862
Authors: Jeffrey J Tosoian; Michael A Gorin; Ashley E Ross; Kenneth J Pienta; Phuoc T Tran; Edward M Schaeffer Journal: Nat Rev Urol Date: 2016-10-11 Impact factor: 14.432