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PURPOSE: To report on planning and toxicity findings of hypofractionated adjuvant radiotherapy with helical Tomotherapy (HTT) after radical prostatectomy (RP) for prostate carcinoma (pCa). METHODS AND MATERIALS: Fifty consecutive patients submitted to RP for pT2R1/pT3a/pT3b-pN0 pCa were enrolled in a Phase I-II trial to receive 58Gy/20 fractions (5/week) on tumoral bed. Endpoint was to verify a risk of toxicity and biochemical failure not exceeding that observed in our Institutional 3DCRT, conventionally fractionated series (153 patients). Toxicities were graded according the RTOG scoring system. RESULTS: Excellent coverage of PTV and high homogeneity of dose distribution were always achieved. Median follow-up was 25 months. Acute G2-3 RTOG genitourinary (GU) and acute G2 intestinal toxicities were similar (12% vs 15.6% and 4% vs 7%, respectively), while acute G2 proctitis was 0% vs 9% in HTT and 3DCRT group, respectively. Similarly, late Grade 2 gastrointestinal sequelae were 0% vs 8.5%. The incidence of late urethral stricture, 8% and 9% in HTT and 3DCRT group, respectively, is comparable to that of RP-only series. CONCLUSIONS: Acute toxicity and early late toxicity outcomes of a moderately hypofractionated regimen with HTT post-RP are excellent. A longer follow-up is needed to fully assess the validity of this approach.