OBJECTIVE: To report the 3-year toxicity and outcome results of 11C-Choline positron emission tomography/computed tomography (11C-Ch-PET/CT)-guided radiotherapy, delivered with helical tomotherapy (Tomotherapy® Hi-Art II® Treatment System, Accuray Incorporated, USA) (HTT) of lymph-nodal (LN) relapses in prostate cancer patients. PATIENTS AND METHODS: From 01/2005 to 03/2013, 81 patients with biochemical recurrence - after surgery±adjuvant/salvage radiotherapy (RT) or radical RT and with evidence of LN 11C-Ch-PET/CT pathological uptake underwent HTT (median PSA: 2.59(0.61-187) ng/ml). 72/81 patients were treated on pelvic and/or lumbar-aortic LN chain with HTT at 51.8 Gy/28 fr and with simultaneous integrated boost (SIB) to a median dose of 65.5 Gy on the pathological uptake sites detected by 11C-Ch-PET/CT. Nine patients were treated without SIB(50-65.5 Gy, 25-30 fr). RESULTS: With a median follow-up of 36 (9-116) months, 91.4% of the patients presented a PSA reduction 3 months after HTT. The 3 year overall, local-relapse-free and clinical-relapse-free survival were 80.0%, 89.8% and 61.8%, respectively. The 3-year actuarial incidences of ≥G2 rectal and ≥G2 GU toxicity were 6.6% (± 2.9%) and 26.3% (±5.5%) respectively. A PSA nadir ≥0.26 ng/ml (HR:3.6; 95%CI 1.7-7.7, p=0.001), extra-pelvic 11C-Ch-PET/CT positive LN location (HR:2.4; 95%CI 0.9-6.4, p=0.07), RT previous to HTT (HR:2.7; 95% CI 1.07-6.9, p=0.04) and number of positive LN (HR:1.13; 95%CI 1.04-1.22, p=0.003) were the main predictors of clinical relapse after HTT . CONCLUSIONS: 11C-Ch-PET/CT-guided HTT is safe and effective in the treatment of LN relapses of previously treated prostate cancer patients. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.