There is currently a lack of level 1 evidence regarding the relative efficacy of radical prostatectomy compared with radiotherapy combined with androgen deprivation therapy for high-risk prostate cancer. There has recently been an improved optimization of treatment, achieving superior biochemical outcomes and cancer-specific mortality through the use of combined modality therapy strategies. Combined modality therapies have also increasingly incorporated brachytherapy boost. Although available observational data must be interpreted with caution because of the effects of potential residual confounding, we present here a narrative review of recent advances in understanding the relative efficacy of the principal combined modality approaches for treating high-risk prostate cancer. As the trend has demonstrated approaching equivalence between well-selected combined modality therapies, an increasing emphasis should be placed on selecting therapy tailored toward a patient's goals regarding quality of life. We present here an outline of efforts to date to understand the implications of treatment on functional outcomes and quality-of-life endpoints.