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Background: Previous prospective randomised trials have shown a positive impact of adjuvant radiation therapy (RT) in patients with locally advanced prostate cancer. However, none of these trials included patients with lymph node invasion (LNI)., Objective: The aim of this study was to assess the impact of combination adjuvant hormonal therapy (HT) and RT on the survival of patients with prostate cancer and histologically documented lymph node metastases (pN+)., Design, Setting, and Participants: Data on 703 consecutive patients with LNI treated with radical prostatectomy, pelvic lymph node dissection, and adjuvant treatments between September 1986 and November 2002 at two large academic institutions were reviewed., Measurements: For study purposes, patients treated with adjuvant HT plus RT and patients treated with adjuvant HT alone were matched for age at surgery, pathologic T stage and Gleason score, number of nodes removed, surgical margin status, and length of follow-up. Differences in cancer-specific survival (CSS) and overall survival (OS) were compared using the Kaplan-Meier method and life table analyses., Results and Limitations: Following the matching process, 117 pT2-4 pN1 patients of 171 (68.4%) treated with adjuvant HT plus RT (group 1) were compared with 247 pT2-4 pN1 patients of 532 (46.4%) receiving adjuvant HT alone (group 2). After matching, the two groups of patients were comparable in terms of pre- and postoperative characteristics (all p ≥ 0.07). Mean follow-up was 100.8 mo (median: 95.1 mo; range: 3.5-229.3 mo). Overall, prostate CSS and OS rates at 5, 8, and 10 yr were 90%, 82%, and 75%, and 85%, 70%, and 60%, respectively. Patients treated with adjuvant RT plus HT had significantly higher CSS and OS rates compared with patients treated with HT alone at 5, 8, and 10 yr after surgery (95%, 91%, and 86% vs 88%, 78%, and 70%, and 90%, 84%, and 74% vs 82%, 65%, and 55%, respectively; p = 0.004 and p<0.001, respectively). Similarly, higher survival rates associated with the combination of HT plus RT were found when patients were stratified according to the extent of nodal invasion (namely, two or fewer vs more than two positive nodes; all p ≤ 0.006). Lack of standardised HT and RT protocols represents the main limitations of our retrospective study., Conclusions: Adjuvant RT plus HT significantly improved CSS and OS of pT2-4 pN1 patients, regardless of the extent of nodal invasion. These results reinforce the need for a multimodal approach in the treatment of node-positive prostate cancer., (Copyright © 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved.)