Objective: We evaluated the effectiveness of stereotactic radiosurgery alone for patients with 1-4 brain metastases without prophylactic whole-brain radiation therapy (WBRT). Materials and Methods: 762 consecutive cases with no more than 4 brain metastases treated under the same local treatment protocol were analyzed. Large tumors (>3 cm in mean diameter) were totally removed or irradiated with hypofractionated stereotatcic radiotherapy using the Gamma Knife (R) (GK), while smaller lesions (<= 3 cm) were all irradiated with GK radiosurgery. No upfront WBRT was applied and new distant lesions were appropriately retreated with GK radiosurgery. Tumor progression-free, overall, neurological, qualitative and new lesion-free survival curves were calculated by the Kaplan-Meier method. Results: In total, I,277 separate GK procedures were required to treat 3,878 lesions. The tumor control rates at I year were 98.0% in tiny (<1 cm in mean diameter), 89.5% in small (<= 1 but <2 cm), 80.1% in medium-sized (<= 2 but <3 cm), and 61.6% in large (>= 3 cm) lesions. The median survival period was 0.77 years. Neurological, qualitative and new lesion-free survival rates at 1 year were 92.0, 85.9 and 63.6%, respectively. New lesions and salvage treatments were more frequent in patients with multiple brain metastases than in those with a single metastasis (p < 0.0001). The number of salvage GK procedures for new distant lesions was zero in 375 (67.0%), one in 91(16.3%), two in 54 (9.6%), and >= 3 in 40 cases (7.1%). Conclusion: In meeting the goal of preventing neurological death and maintaining activities of daily living for patients with 1-4 brain metastases from various cancers, GK alone provides excellent palliation without prophylactic WBRT. New distant lesions were quite well controlled with salvage GK treatment alone. Copyright (C) 2010 S. Karger AG, Basel