Background: This study summarizes long-term outcomes from treatment of prostate cancer with increased risk of extracapsular cancer extension (ECE) using brachytherapy-based treatment., Methods: A total of 282 consecutive patients were treated from 1992-1996 by 1 author (M.D.). Two hundred forty-three patients had at least 1 higher risk feature for ECE including Gleason Score 7-10 (172), prostate-specific antigen (PSA) above 10 (166), and clinical stages T(2c) (109) and T(3) (107). Using National Comprehensive Cancer Network (NCCN) guidelines, 119 patients had intermediate-risk disease and 124 had high-risk disease. Patients received pelvic 3-dimensional conformal external beam radiation followed by a palladium (Pd)-103 boost. Generous brachytherapy margins were utilized. Biochemical failure was defined using ASTRO Consensus Definition, nadir +2 and PSA >0.2 ng/mL at last follow-up. The nonfailing patient follow-up period was 1-14 years (median, 9.5 years). Biochemical data and original biopsy slides were independently re-reviewed at the University of Washington (by K.W. and L.T., respectively)., Results: Overall actuarial freedom from biochemical progression at 14 years was 81%, including 87% and 72% having intermediate and high-risk disease, respectively. Absolute risk of failure decreased progressively, falling to 1% beyond 6 years after treatment. All failing patients had prostate biopsies without evidence of local recurrence. The strongest predictor of failure was Gleason score (P = .03) followed by PSA (P = .041). Treatment morbidity was limited to temporary RTOG grade 1-2 urinary and gastrointestinal symptoms., Conclusions: High tumor control rates are possible with beam radiation followed by Pd-103 brachytherapy. Despite perceptions that brachytherapy is inappropriate for patients at higher risk for ECE, this series strengthens the rationale that brachytherapy-based treatment may be a desirable modality for such patients., ((c) 2007 American Cancer Society.)