Background: Hormone therapy plus radiotherapy significantly decreases recurrences and mortality of patients affected by locally advanced prostate cancer (PCa). Controversy remains about the optimal duration of androgen deprivation (AD) when associated to high-dose radiotherapy (HDRT). This trial was designed to determine whether long-term AD (LTAD) is superior to short-term AD (STAD) in the setting of HDRT Methods: Eligibility included patients with cT1c-T3aN0M0 adenocarcinoma of prostate with intermediate and high risk factors according to NCCN criteria and PSA less than 100 ng/ml. All patients received 4 months of neoadjuvant and concomitant AD (STAD) + HDRT (minimum dose to the prostate 76 Gy) before randomization to adjuvant gosereline (LTAD) for two years. Stratification was performed according to risk group (intermediate risk [IR] versus high risk [HR]). Study endpoints included overall survival (OS), metastasis free survival (MFS), disease free survival (DFS) and biochemical-disease free survival (bDFS). Initial analysis of results is reported. Results: A total of 361 men were registered, of whom 180 were randomly assigned to STAD (97 HR and 83 IR) and 181 to LTAD (94 HR and 87 IR). Median isocenter radiation dose to the prostate was 78.0 Gy for both groups. Elective pelvic radiotherapy was administered in 28 patients treated with STAD and in 20 patients with LTAD. Demographic data, tumour and treatment characteristics were evenly distributed in the two arms. After a median follow-up of 30 months, 9 patients in the STAD group (2 intermediate risk and 7 high risk PCa) and none in the LTAD group had biochemical failure according to Phoenix definition (p=0.002). The median time to biochemical relapse was 28 months. Four patients developed distant metastasis (all of them in the STAD arm) and 3 patients have died from causes other than PCa. Grade ≥ 2 radiation related adverse effects in both arms were not statistically significant. Conclusions: Although preliminary, the results of the present study suggest that LTAD could be superior to STAD in patients with unfavourable PCa treated with HDRT.