Background. The benefit of dose-escalated hypofractionated radiotherapy using intensity-modulated radiotherapy (IMRT) in prostate cancer is not established. We report 5-year outcome and long-term toxicity data within a phase II clinical trial. Materials and Methods. 60 men with predominantly high-risk prostate cancer were treated. All patients received neoadjuvant hormone therapy, completing up to 6 months in total. Thirty patients were treated with 57？Gy in 19 fractions and 30 patients with 60？Gy in 20 fractions. Acute and 2-year toxicities were reported and patients followed longitudinally to assess 5 year outcomes and long-term toxicity. Toxicity was measured using RTOG criteria and LENT/SOMA questionnaire. Results. Median followup was 84 months. Five-year overall survival (OS) was 83% and biochemical progression-free survival (bPFS) was 50% for 57？Gy. Five-year OS was 75% and bPFS 58% for 60？Gy. At 7 years, toxicity by RTOG criteria was acceptable with no grade 3 or above toxicity. Compared with baseline, there was no significant change in urinary symptoms at 2 or 7 years. Bowel symptoms were stable between 2 and 7 years. All patients continued to have significant sexual dysfunction. Conclusion. In high-risk prostate cancer, dose-escalated hypofractionated radiotherapy using IMRT results in encouraging outcomes and acceptable late toxicity. 1. Introduction Dose-escalated radiotherapy improves local and biochemical disease control in localised prostate cancer [1–4]. However, this is at the expense of increased late normal tissue toxicity and overall treatment time [3–6].There is increasing evidence that the α/β ratio for prostate cancer may be low [7–9], and in one analysis of nearly 6000 patients the calculated α/β ratio was 1.4 [10]. This suggests that a hypofractionated regimen should be biologically advantageous. A shortened overall treatment time also provides benefits in terms of patient acceptability and health economics [11]. Our group has previously published data on patients treated with 50？Gy in 16 daily fractions (equivalent total dose of 66？Gy, assuming an α/β ratio for prostate cancer of 1.5) [12]. However, the biochemical outcome for patients with intermediate or high risk disease was inferior to dose-escalated series using 2？Gy per fraction [13]. This finding was replicated in a later study using low-dose hypofractionated radiotherapy [14]. Although there is evidence for improved bPFS with increasing doses of radiotherapy, no overall survival benefit has yet been demonstrated. Indeed, the MRC RT01 study showed equivalent overall
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