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Purpose: High-dose-rate brachytherapy (HDR-BT) with external beam radiation therapy (EBRT) is a common treatment option for locally advanced prostate cancer. Quality of life is an important factor when discussing therapy options for high-risk prostate cancer. This study evaluated adverse effects and health-related quality of life (HRQOL). Materials and Methods: Ninety male patients (median age, 71 years; range, 50 to 79 years) with high-risk prostate cancer underwent HDR-BT after EBRT between December 2009 and January 2017 with a median follow-up of 43 months. A total of 57 patients (69.5%) answered the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life of Cancer Patients questionnaire (QLQ-C30; ver. 3.0), and 8 patients died during follow-up. In order to put the results of this study in context, we compared the results with reference data from the EORTC QLQ-C30 Scoring Manual. Correlations of prostate-specific antigen (PSA) values, International Prostate Symptom Score, and HRQOL measures were calculated. Results: The study participants reported better physical functioning and better global health compared with the reference data, but worse social, role, and cognitive functioning. We found negative statistically significant correlations between the last-measured PSA value and social functioning (p>0.01), cognitive functioning, pain, and constipation (all p