group; grade >3 diarrhoea, 4 patients (0.7%) versus 8 (1.3%); grade >3 urinary toxicity, 14 patients (2.3%) in both groups). The benefits of combined modality treatment — ADT and radiotherapy — should be discussed with all patients with locally advanced prostate cancer. 2.6. RECTAL CANCER Pre-operative chemoradiotherapy has been established as standard treatment for locally advanced rectal cancer after the first results of the German Cancer Society trial, published in 2004 [2.18], showed an improved local control rate. However, after a median follow-up of 46 months, no survival benefit could be shown. Here, we report long term results of this study with a median follow-up of 134 months [2.19]. A total of 823 patients with stage II to III rectal cancer were randomly assigned to pre-operative chemoradiotherapy with 5-FU, total mesorectal excision surgery and adjuvant 5-FU chemotherapy, or the same schedule of chemoradiotherapy used post-operatively. The study was designed to have 80% power to detect a difference of 10% in five year overall survival as the primary 35 end point. Secondary end points included the cumulative incidence of local and distant relapses and disease free survival. Of 799 eligible patients, 404 were randomly assigned to pre-operative chemoradiotherapy and 395 to post-operative chemoradiotherapy. According to intention-to-treat analysis, overall survival at ten years was 59.6% in the pre-operative arm and 59.9% in the post-operative arm (p = 0.85). The ten year cumulative incidence of local relapse was 7.1% and 10.1% in the pre- and post-operative arms, respectively (p = 0.048). No significant differences were detected for ten year cumulative incidence of distant metastases (29.8% and 29.6%; p = 0.9) and disease free survival. There was a persistent significant improvement of pre- versus post-operative chemoradiotherapy on local control; however, there was no effect on overall survival. More effective systemic treatment has been integrated into the multimodal therapy in the CAO/ARO/AIO-04 trial to possibly reduce distant metastases and improve survival. Other advantages of pre-operative chemoradiotherapy include a reduction in acute toxicities as the treatment volumes become smaller, the potential to convert some patients from an abdominoperineal resection (APR) to a low anterior resection (LAR) and the potential to convert some patients from inoperable to operable status. A coordinated research project (CRP) by the IAEA is currently testing standard chemoradiotherapy (50 Gy in 25 fractions with 5-FU/leucovorin or capecitabine) versus a short fractionation of 25 Gy in five fractions of 5 Gy in one week as pre-operative treatment in inoperable or borderline inoperable rectal cancer patients. End points are survival, operability conversion rate and toxicity. 2.7. OESOPHAGEAL CANCER To compare the locoregional control, survival and toxicity of combined modality therapy using high dose (64.8 Gy) versus standard dose (50.4 Gy) radiotherapy for the treatment of patients with oesophageal cancer, a total of 236 patients with clinical stage T1 to T4, N0/1, M0 squamous cell carcinoma or adenocarcinoma were randomized [2.20]. Patients selected for a non-surgical approach were randomized to receive combined modality therapy consisting of four monthly cycles of 5-FU (1000 mg/m2 per day for 4 days) and cisplatin (75 mg/m2 bolus day 1) with concurrent 64.8 Gy versus the same chemotherapy schedule, but with concurrent 50.4 Gy. The trial was stopped after an interim analysis. The median follow-up was 16.4 months for all patients and 29.5 months for patients still alive. For the 218 eligible patients, there was no significant difference in median survival (13.0 versus 18.1 months), two year survival (31% versus 40%), or 36 locoregional failure and locoregional persistence of disease (56% versus 52%) between the high dose and standard dose arms. Although 11 treatment related deaths occurred in the high dose arm compared with 2 in the standard dose arm, 7 of the 11 deaths occurred in patients who had received 50.4 Gy or less. The higher radiation dose did not increase survival or locoregional control. Although there was a higher treatment related