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)

• 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.

• 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)

-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

• 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.

• 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.