Standard therapy for clinically localized prostate cancer includes radical prostatectomy, external beam radiotherapy, or transperineal interstitial brachytherapy. Patients eligible for standard therapy are those with low risk features as defined by various risk group classifications, which generally include clinical stage T1 or T2a, serum prostate-specific antigen (PSA) less than 10 ng/mL, and biopsy Gleason sum of 6 or less. Although there has been important evolution in the performance of these techniques, particularly with respect to functional outcomes, these approaches for low-risk disease are relatively mature, and the cure rates with each of these therapies are similar in this patient population; locally advanced disease is more difficult to cure, however. Biochemical disease-free survival rates in men undergoing radical prostatectomy are clearly related to the pathologic stage. Prognostic groups can be defined based on pathologic stage with increasingly worse outcomes based on extracapsular extension (ECE), margin status, and the status of the lymph nodes and seminal vesicles. In patients with low risk features, the positive margin rate is generally low, making the presence or absence of ECE the dominant variable in predicting the likelihood of treatment failure. These observations suggest that more aggressive therapy is needed to cure those who are likely to have ECE or other adverse histologic features. Several nomograms predicting the likelihood of ECE or 5-year biochemical failure rates are now in routine clinical use, and can be used to select men at high risk of failure with single modality therapy for more aggressive treatment strategies. However, the optimal form of aggressive therapy for these patients is unknown.