Late Radiation and Cardiovascular Adverse Effects After Androgen Deprivation and High-Dose Radiation Therapy in Prostate Cancer: Results From the DART 01/05 Randomized Phase 3 Trial.
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).



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.



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.



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.
Hospital Universitario de la Princesa, Madrid, Spain. Electronic address: almudena.zapatero@salud.madrid.org.
Almudena
A
Zapatero
Hospital Son Espases, Palma de Mallorca, Spain.
Araceli
A
Guerrero
Hospital Universitari Vall d'Hebron, Barcelona, Spain.
Xavier
X
Maldonado
Hospital General Universitario Gregorio Marañón, Madrid, Spain.
Ana
A
Álvarez
Hospital General Universitario Gregorio Marañón, Madrid, Spain.
Carmen
C
González-San Segundo
Hospital Universitario 12 de Octubre, Madrid, Spain.
Maria Angeles
MA
Cabeza Rodriguez
Hospital General de Catalunya, Sant Cugat del Vallès and Hospital Universitario de Salamanca, Salamanca, Spain.
Victor
V
Macías
Hospital Plató, Barcelona, Spain.
Agustí
A
Pedro Olive
Hospital Clinic, Barcelona, Spain.
Francesc
F
Casas
Institut Català d'Oncologia, Barcelona, Spain.
Ana
A
Boladeras
Hospital Universitario de la Princesa, Madrid, Spain.
Carmen
C
Martín de Vidales
Hospital Do Meixoeiro, Vigo, Spain.
Maria Luisa
ML
Vázquez de la Torre
Hospital General Universitario Gregorio Marañón, Madrid, Spain.
Felipe A
FA
Calvo
D000726:Androgen Antagonists / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000401:mortality*; D015984:Causality; D059248:Chemoradiotherapy / Q000401:mortality; D015897:Comorbidity; D018572:Disease-Free Survival; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D015995:Prevalence; D011471:Prostatic Neoplasms / Q000401:mortality* / Q000628:therapy*; D000069473:Radiation Dose Hypofractionation; D011832:Radiation Injuries / Q000401:mortality*; D018570:Risk Assessment; D013030:Spain / Q000453:epidemiology; D015996:Survival Rate; D016896:Treatment Outcome
D000726:Androgen Antagonists