BACKGROUND: Because of their rarity, no prospective studies have been performed regarding gangliogliomas. The optimal treatment regimen is unclear. In this study, the authors compared 4 therapies for local control (LC) and overall survival (OS) in patients with ganglioglioma. METHODS: In 402 patients with ganglioglioma, outcomes were compared for patients who underwent gross total resection alone (GTR) (n ¼ 188), GTR plus radiotherapy (GTR þ RT) (n ¼ 21), subtotal resection alone (STR) (n ¼ 113), and STR plus RT (STR þ RT (n ¼ 80). Age, sex, tumor site, and histologic grade also were investigated. Subgroup analyses were performed for both low-grade and high-grade tumors. RESULTS: The 10-year LC rates were 89% after GTR, 90% after GTR þ RT, 52% after STR, and 65% after STR þ RT (P < .001); and the 10-year OS rates were 95%, 95%, 62%, and 74%, respectively (P < .001). After STR, irradiation significantly improved LC (P ¼ .004) but not OS (P ¼ .22). After GTR, irradiation did not significantly improve LC (P ¼ .23) or OS (P ¼ .29). On multivariate analyses, LC and OS were associated with therapy and pathologic grade, and OS also was associated with tumor site. In low-grade tumors, STR þ RT resulted in better LC (P ¼ .016) but not better OS (P ¼ .18); and, after GTR, LC (P ¼ .28) and OS (P ¼ 1.0) were not improved with postoperative radiotherapy. In highgrade tumors, STR þ RT resulted in better LC (P ¼ .016) but not better OS (P ¼ .41); after GTR, LC (P ¼ .56) and OS (P ¼ .61) were not improved with irradiation. CONCLUSIONS: According to this review, GTR should be performed whenever safely possible and does not require postoperative irradiation. If only STR is achieved, then RT improves LC of both low-grade and high-grade tumors and, thus, should be considered seriously. Cancer 2010;116:432-42.