A number of recent studies have successfully reduced the number of radiotherapy treatments used for prostate cancer from 39 daily treatments to as little as 5 treatments. This study is designed to determine how tumors inside the prostate respond during these 5 treatments on magnetic resonance imaging (MRI) and use that information to design 2 fraction radiotherapy treatments for prostate cancer.

For these two fraction treatments, the first fraction of radiation will use extra radiation to any nodules in the prostate, and the second fraction of radiation will give extra radiation to the nodule(s) in the prostate based on how those nodules responded to the first fraction of radiation. This idea is a relatively old concept but has not been used in the treatment of cancer yet. This research includes a clinical trial that evaluates whether it is safe to design treatments like this.

Inclusion Criteria:

• Histologically confirmed adenocarcinoma of the prostate
• NCCN risk grouping of intermediate or high risk prostate cancer
• Patients must be 18 years of age, or older on the day of signing informed consent and be willing and able to provide written informed consent/assent
• Identifiable lesion within the epithelium of the prostate as determined by the treating radiation oncologist
• Have a prostate imaging reporting and data system (PIRADS) 4 or 5 nodule noted on MRI
• Have not received prior pelvic radiotherapy
• Life expectancy greater than 10 years
• ECOG performance status <3
• Eligible for SBRT to the prostate

Exclusion Criteria:

• No identifiable lesion within the prostate on 3T MRI
• Prior trans-urethral resection of the prostate
• Non-adenocarcinoma histology
• Meeting criteria for very high-risk risk or node positive prostate cancer
• Active inflammatory bowel disease
• Evidence of metastatic disease on CT or bone scan
• Declined radiotherapy
• Unlikely to be available for all follow-up appointments
• Having received androgen deprivation therapy or 5-alpha reductase therapy prior to trial therapy
• Extensive disease in the posterior prostate or aberrant anatomy that makes the safe delivery of boost irradiation not feasible
• Unable to understand or sign a study consent form after use of interpreter if required
• Has a relative contraindication to radiotherapy including systemic lupus erythematosus, TNM deficiency or scleroderma
• Unable to tolerate or ineligible for mpMR imaging
• Any condition or diagnosis, that could in the opinion of the treating physician or qualified investigator interfere with the participant's ability to comply with study instructions, might confound the interpretation of the study results, or put the participant at risk

biological male