PURPOSE: To present data on the late toxicity endpoints of a randomized trial (DART 01/05) conducted to determine whether long-term androgen deprivation (LTAD) was superior to short-term AD (STAD) when combined with high-dose radiation therapy (HDRT) in patients with prostate cancer (PCa). PATIENTS AND METHODS: Between November 2005 and December 2010, 355 eligible men with cT1c-T3aN0M0 PCa and intermediate-risk and high-risk factors (2005 National Comprehensive Cancer Network criteria) were randomized to 4 months of AD combined with HDRT (median dose, 78 Gy) (STAD) or the same treatment followed by 24 months of AD (LTAD). Treatment-related complications were assessed using European Organization for Research and Treatment of Cancer-Radiation Therapy Oncology Group and Common Terminology Criteria for Adverse Events v3.0 scoring schemes. Multivariate analyses for late toxicity were done using the Fine-Gray method. RESULTS: The 5-year incidence of grade ≥2 rectal and urinary toxicity was 11.1% and 8.2% for LTAD and 7.6% and 7.3% for STAD, respectively. Compared with STAD, LTAD was not significantly associated with a higher risk of late grade ≥2 rectal toxicity (hazard ratio [HR] 1.360, 95% confidence interval [CI] 0.660-2.790, P=.410) or urinary toxicity (HR 1.028, 95% CI 0.495-2.130, P=.940). The multivariate analysis showed that a baseline history of intestinal comorbidity (HR 3.510, 95% CI 1.560-7.930, P=.025) and the rectal volume receiving >60 Gy (Vr60) (HR 1.030, 95% CI 1.001-1.060, P=.043) were the only factors significantly correlated with the risk of late grade ≥2 rectal complications. A history of previous surgical prostate manipulations was significantly associated with a higher risk of grade ≥2 urinary complications (HR 2.427, 95% CI 1.051-5.600, P=.038). Long-term AD (HR 2.090; 95% CI 1.170-3.720, P=.012) and a history of myocardial infarction (HR 2.080; 95% CI 1.130-3.810, P=.018) were significantly correlated with a higher probability of cardiovascular events. CONCLUSION: Long-term AD did not significantly impact urinary or rectal radiation-induced toxicity, although it was associated with a higher risk of cardiovascular events. Longer follow-up is needed to measure the impact of AD on late morbidity and non-PCa mortality.
RCT Entities:
PURPOSE: To present data on the late toxicity endpoints of a randomized trial (DART 01/05) conducted to determine whether long-term androgen deprivation (LTAD) was superior to short-term AD (STAD) when combined with high-dose radiation therapy (HDRT) in patients with prostate cancer (PCa). PATIENTS AND METHODS: Between November 2005 and December 2010, 355 eligible men with cT1c-T3aN0M0 PCa and intermediate-risk and high-risk factors (2005 National Comprehensive Cancer Network criteria) were randomized to 4 months of AD combined with HDRT (median dose, 78 Gy) (STAD) or the same treatment followed by 24 months of AD (LTAD). Treatment-related complications were assessed using European Organization for Research and Treatment of Cancer-Radiation Therapy Oncology Group and Common Terminology Criteria for Adverse Events v3.0 scoring schemes. Multivariate analyses for late toxicity were done using the Fine-Gray method. RESULTS: The 5-year incidence of grade ≥2 rectal and urinary toxicity was 11.1% and 8.2% for LTAD and 7.6% and 7.3% for STAD, respectively. Compared with STAD, LTAD was not significantly associated with a higher risk of late grade ≥2 rectal toxicity (hazard ratio [HR] 1.360, 95% confidence interval [CI] 0.660-2.790, P=.410) or urinary toxicity (HR 1.028, 95% CI 0.495-2.130, P=.940). The multivariate analysis showed that a baseline history of intestinal comorbidity (HR 3.510, 95% CI 1.560-7.930, P=.025) and the rectal volume receiving >60 Gy (Vr60) (HR 1.030, 95% CI 1.001-1.060, P=.043) were the only factors significantly correlated with the risk of late grade ≥2 rectal complications. A history of previous surgical prostate manipulations was significantly associated with a higher risk of grade ≥2 urinary complications (HR 2.427, 95% CI 1.051-5.600, P=.038). Long-term AD (HR 2.090; 95% CI 1.170-3.720, P=.012) and a history of myocardial infarction (HR 2.080; 95% CI 1.130-3.810, P=.018) were significantly correlated with a higher probability of cardiovascular events. CONCLUSION: Long-term AD did not significantly impact urinary or rectal radiation-induced toxicity, although it was associated with a higher risk of cardiovascular events. Longer follow-up is needed to measure the impact of AD on late morbidity and non-PCa mortality.
Authors: Robert T Dess; Todd M Morgan; Paul L Nguyen; Rohit Mehra; Howard M Sandler; Felix Y Feng; Daniel E Spratt Journal: Curr Urol Rep Date: 2017-07 Impact factor: 3.092
Authors: A Zapatero; M Roch; D Büchser; P Castro; L Fernández-Banda; G Pozo; O Liñán; C Martin de Vidales; A Cruz-Conde; F García-Vicente Journal: Clin Transl Oncol Date: 2017-04-03 Impact factor: 3.405
Authors: Nicholas G Zaorsky; James B Yu; Sean M McBride; Robert T Dess; William C Jackson; Brandon A Mahal; Ronald Chen; Ananya Choudhury; Ann Henry; Isabel Syndikus; Timur Mitin; Alison Tree; Amar U Kishan; Daniel E Spratt Journal: Adv Radiat Oncol Date: 2020-10-29
Authors: Reith R Sarkar; Ahmadreza Hatamipour; Neil Panjwani; P Travis Courtney; Daniel R Cherry; Mia A Salans; Anthony T Yip; Brent S Rose; Daniel R Simpson; Matthew P Banegas; James D Murphy Journal: Am J Clin Oncol Date: 2021-06-01 Impact factor: 2.787
Authors: Nicholas G Zaorsky; James B Yu; Sean M McBride; Robert T Dess; William C Jackson; Brandon A Mahal; Ronald Chen; Ananya Choudhury; Ann Henry; Isabel Syndikus; Timur Mitin; Alison Tree; Amar U Kishan; Daniel E Spratt Journal: Adv Radiat Oncol Date: 2020-04-01
Authors: Robert T Dess; Yilun Sun; William C Jackson; Neil K Jairath; Amar U Kishan; David G Wallington; Brandon A Mahal; Bradley J Stish; Zachery S Zumsteg; Robert B Den; William A Hall; Laila A Gharzai; Elizabeth M Jaworski; Zachary R Reichert; Todd M Morgan; Rohit Mehra; Edward M Schaeffer; Oliver Sartor; Paul L Nguyen; William Robert Lee; Seth A Rosenthal; Jeff M Michalski; Matthew J Schipper; James J Dignam; Thomas M Pisansky; Anthony L Zietman; Howard M Sandler; Jason A Efstathiou; Felix Y Feng; William U Shipley; Daniel E Spratt Journal: JAMA Oncol Date: 2020-05-01 Impact factor: 31.777