As is common with other tumor systems in which radiation therapy is delivered for therapeutic benefit, an overarching paradigm in prostate cancer radiation therapy is the application of appropriate evidence-based dosages to the cancer target while simultaneously avoiding sensitive adjacent normal tissues. In this way, the therapeutic ratio between tumor control and normal tissue injury is established to maximize therapeutic benefit while minimizing toxicity, morbidity, and potentially treatment-related mortality. Over the past few decades, the specialty of radiation oncology has leveraged various technologies to achieve this goal of improved cancer outcomes with equal or improved toxicity profiles. A variety of approaches exist to optimize the therapeutic ratio in radiation oncology. A non-exhaustive list of these approaches includes the following: <ul> <li>Simulation procedures: Bladder/rectum filling instructions, patient immobilization, placement of fiducial markers, and use of rectal spacers</li> <li>Imaging procedures: CT simulations, integrations of fusion imaging (e.g., MRI prostate), image-guided radiation therapy (IGRT) approaches (e.g., cone-beam CT)</li> <li>Planning procedures: Use of highly conformal radiation therapy such as IMRT, volumetric modulated arc therapy (VMAT), and stereotactic body radiation therapy (SBRT), combined with published target and normal tissue dose objectives to optimize planning</li> </ul> Most of these approaches have not been subject to prospective randomized phase III trial testing. One exception is the use of rectal spacers, which was evaluated in a trial that randomized 222 patients 2:1 to either a rectal spacer or control group prior to 79.2 Gy in 1.8 Gy fractions to the prostate ± seminal vesicles.224, 225 With a median follow-up of three years, improvements in low-grade (one and two) rectal toxicity, no difference in urinary toxicity, and improvements in bowel health-related QOL were identified.225 Device-related toxicity events were not detected in this trial.224 Of note, the utility of this technology in conjunction with hypofractionated or ultra hypofractionated radiation therapy has not been reported in prospective randomized clinical trials to date.