With the introduction of modern treatment planning software and CT scans in the late 1980s and early 1990s, radiation oncology techniques evolved from basic conventional techniques using simple 2-dimensional planning. Prior to the implementation of sophisticated treatment planning software and CT scans, radiation doses used in the treatment of prostate cancer were limited to between 65-70 Gy. Advances in radiation treatment planning software and imaging technology have allowed delivery of higher doses to the prostate while limiting doses to the surrounding normal tissues such as rectum and bladder, thus improving the therapeutic ratio.226, 227 The current standard technique of EBRT is IMRT, which allows dose escalation to greater than 80 Gy safely. Since the 1990s, multiple phase III randomized prospective studies have compared dose-escalated EBRT (DE-EBRT) using both 3-D conformal radiation therapy (3DCRT) and IMRT with standard dose EBRT and have consistently demonstrated improved biochemical PFS with dose escalation. Multiple randomized trials (sample sizes 126 to 1,499) compared escalated versus conventional dose radiation therapy in patients with localized prostate cancer.228-242 The trials enrolled a mix of low-, intermediate-, and high-risk patients. Escalated doses ranged from 74 to 79.2 Gy, while conventional doses ranged from 64 to 70.2 Gy. The trials consistently demonstrated that escalated dose radiation therapy was associated with decreased rates of biochemical failure or recurrence. Of note, the Panel acknowledges that estimates from these trials for the endpoints of metastatic-disease free survival, prostate cancer-specific survival, and OS were imprecise and did not indicate a benefit to dose escalation, with the exception of one trial236, 238, 240 that did report reduced risks of distant metastatic failure (HR 0.33, 95% CI 0.13 to 0.82) and prostate cancer mortality (HR 0.52, 95% CI 0.27 to 0.98). The largest of the trials was NRG-RTOG 0126 (n=1,499) which looked at standard versus dose-escalated radiation therapy in patients with intermediate-risk prostate cancer.237 This trial demonstrated improvements in biochemical failure and distant metastases; however, the dose-escalated radiation therapy arm was not associated with improvements in OS. Furthermore, higher radiation doses were also associated with lower rates of post-radiation salvage at the expense of higher rates of late toxicity. Importantly, this trial has provided clinicians valuable information about radiation dose constraints for the safe planning of dose-escalated radiation therapy for intermediate-risk prostate cancer.243