QUESTIONS UNDER STUDY/PRINCIPLES: A retrospective assessment of long-term results on a single centre, single author experience in treating prostate cancer with high dose curative radiotherapy (RT) with or without androgen deprivation (AD). METHODS: Between 1991 and 2004, 408 patients with clinically localised prostate cancer were treated with RT (+/-AD) at the University Hospital of Geneva. RT alone was delivered to 229 patients whereas AD associated to RT was given to 179 patients. The latter was most frequently delivered to those patients with worse prognostic factors at diagnosis (high PSA values, high Gleason scores, stage T3-T4; p <0.001). Patient's biochemical failure was established at the time of PSA progression above the post-treatment nadir value +2 ng/ml. Late urinary, rectal, and sexual side effects were assessed and scored according to the Radiotherapy Oncology Group grading system. RESULTS: Ten-year overall survival (OS) and cancer specific survival were 93% and 62% (p = 0.10), and 94% and 71% (p = 0.19) for patients treated with RT with and without AD respectively (p = 0.10). Ten-year biochemical disease-free survival (bDFS) was 61% and 50% for patients treated with RT with and without AD, respectively (p = 0.14). On Cox regression analysis, PSA at diagnosis and treatment modality correlated significantly with OS, whereas PSA at diagnosis, Gleason score, and treatment modality correlated significantly with bDFS. Mostly high-risk patients (PSA >20 ng/ml and/or Gleason 8-10) benefited from neo-adjuvant AD+RT compared to patients treated with RT alone (67% versus 32%, 5-year bDFS; p <0.001). The 5-year probability of moderate to severe late urinary and low-GI toxicities was 15% and 7% respectively. Regarding sexual toxicity, the 5-year risk of complete failure of erections after treatment was 57%. CONCLUSIONS: AD+RT significantly improved both 10-year OS and bDFS, especially in patients with high-risk disease at diagnosis. Patients treated with RT alone presented with continuous failures during the 10-year interval of observation, thus questioning the wisdom of proposing RT alone at doses below 74 Gy, especially for patients with long life expectancies.