1. Long-Term versus Short-Term Androgen Deprivation Combined with High-Dose Radiotherapy for Intermediate and High Risk Prostate Cancer: Preliminary Results of a Phase III Randomized Trial - DART 01/05 A.Zapatero, A.Guerrero, X.Maldonado, A.Alvarez, C.González Sansegundo, A.Cabeza, V.Macías, F.Casas. A. Pedro-Olivé, S.Villa, A.Boladeras, M.L. Vazquez de la Torre, C. Martin de Vidales, F.A.Calvo. G.I.C.O.R. This study has been supported by Governmental Grant No. 04/2506 fron the FIS (National Health Investigation Fund – Fondo de Investigación Sanitaria)

2. Background 1.In locally advanced prostate cancer, randomized trials have shown a significant benefit in OS when androgen deprivation (AD) and conventional dose of radiotherapy (≤ 70-72 Gy) are associated. 2. A GICOR study (JCO, 2005) showed and independent benefit of dose escalation combined with AD in high-risk disease. 3.The role and the optimal scheme of AD when associated to high-dose radiotherapy remains controversial.

3. Objectives / Purpose To determine whether long-term AD (LTAD) is superior to short -term AD (STAD) in intermediate and high-risk prostate cancer patients treated with high-dose RT. 1.Primary endpoint: Freedom from biochemical failure (FFBF). (Phoenix definition) 2.Secondary endpoints: Freedom from clinical failure (FFCF) Overall survival (OS) Toxicity (RTOG and CTC criteria)

4. - Study designed to detect a difference in FFBF of 15% in favor of LTAD with a statistical power of 80% and a unilateral significance level of 5%. -Sample size required including 15% loss: 358 patients

8. Limitations of the study  This study assumes the inherent limitations of an interim analysis report:  Short follow-up  Short number of events  Absence of a control arm with HDRT alone ?  FFBF less than optimal primary endpoint? Strenght of the study  This is a pioneering study to evaluate the role of AD combined with high- dose escalated RT (median 78 Gy) in prostate cancer.

9. Conclusion 1.Although preliminary, the results of the study suggest that LTAD could be superior to STAD in patients with unfavorable prostate cancer treated with high-dose external beam radiotherapy. 2.Relevant radiation toxicity remains acceptably low and not significantly different in both treatment arms. 3.Longer follow-up is required to confirm these trends.