Late Radiation and Cardiovascular Adverse Effects following Androgen Deprivation and High-Dose Radiotherapy in Prostate Cancer : Results from the DART 01/05 Randomized Phase III Trial
Mené sur 355 patients atteints d'un cancer de la prostate de stade cT1c-T3aN0M0 à risque intermédiaire ou élevé de récidive et ayant reçu entre 2005 et 2010 un traitement anti-androgénique en combinaison avec une radiothérapie à forte dose de rayonnements ionisants, cet essai de phase III évalue, en fonction de la durée du traitement anti-androgénique, les complications urinaires, rectales et cardiovasculaires à long terme
Purpose : A randomized trial (XX) was conducted to determine whether long-term AD (LTAD) was superior to short-term AD (STAD) when combined with high-dose radiotherapy (HDRT) in patients with prostate cancer (PCa). We present data on the late toxicity endpoints. Patients and Methods : Between November 2005 and December 2010, 355 eligible men with cT1c-T3aN0M0 PCa and intermediate-risk and high-risk factors (2005 NCCN 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 EORTC-RTOG and CTCAEs 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 (HR: 1.360, 95%CI: 0.660-2.790, p=0.410) or urinary toxicity (HR: 1.028, 95%CI: 0.495-2.130, p=0.940). The multivariate analysis showed that a baseline history of intestinal comorbidity (HR: 3.510, 95%CI: 1.560-7.930, p=0.025) and the rectal volume receiving >60Gy (Vr60) (HR: 1.030, 95%CI: 1.001-1.060, p=0.043) 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=0.038). LTAD (HR: 2.090; 95% CI: 1.170-3.720, p=0.012) and a history of MI (HR: 2.080; 95% CI: 1.130-3.810, p=0.018) were significantly correlated with a higher probability of CV events. Conclusion : LTAD did not significantly impact urinary or rectal radiation-induced toxicity, although it was associated with a higher risk of CV events. Longer follow-up is needed to measure the impact of AD on late morbidity and non-PCa mortality.