Trial data support the use of dose-escalated hypofractionated EBRT or brachytherapy including temporary high-dose rate (HDR) or permanent low-dose rate (LDR) prostate implants as appropriate treatment options for patients with low- or favorable intermediate-risk prostate cancer.261 Importantly, the systematic review undertaken for guideline development identified no randomized trials comparing EBRT to brachytherapy. Of note, a retrospective analysis among patients with intermediate-risk prostate cancer (n=684) found no difference between EBRT (75.3 Gy) versus brachytherapy (radioactive iodine seeds at minimum peripheral dose of 145 Gy), with or without neoadjuvant ADT, in propensity score adjusted 10-year MFS (91% versus 94%), prostate cancer-specific survival (96% versus 95%), or OS (76% versus 78%).262 EBRT was associated with decreased likelihood of freedom from biochemical failure (57% versus 80%). To note as well, in a Phase II trial of 170 patients randomized to receive HDR as either a single (19 Gy) fraction or as two fractions (13.5 Gy), the 5-year biochemical disease-free survival and cumulative incidence of local failure was 73.5% and 29% in the single fraction arm and 95% (p = 0.001) and 3% (p < 0.001) in the 2-fraction arm, respectively.263 Toxicity results from this study were reported separately; in the single fraction arm, the 5-year cumulative incidence of Grade 2 or higher genitourinary and gastrointestinal toxicity was 62% and 12%, and was 47% and 9% in the two-fraction arm. Grade 3 genitourinary toxicity was only seen in the single fraction arm. No significant differences in mean urinary health related QOL were seen compared to baseline in the two-fraction arm, in contrast to the single-fraction arm, wherein a decline in urinary health-related QOL was seen at 4 and 5 years. The authors ultimately concluded that both single fraction and 2-fraction HDR monotherapy were well tolerated.264