Inclusion Criteria:
1. Patients age 18 or older.
2. Patients with an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
3. Patients with histologically confirmed adenocarcinoma of the prostate who have not received prior pelvic radiation therapy or prostatectomy.
4. Patients with low to intermediate risk group defined by the NCCN (National Comprehensive Cancer Network) guidelines as follows:
* Low risk prostate cancer:
* cT1-cT2a (AJCC; 8TH edition, 2017)
* Grade Group 1 (GG1)
* PSA \<10 ng/mL
* Intermediate risk prostate cancer:
* cT2b-cT2c (AJCC; 8TH edition, 2017)
* Grade Group 2 (GG2) or Grade Group 3 (GG3)
* PSA 10-20 ng/mL
5. Patients with unfavorable intermediate risk prostate cancer defined by the NCCN guidelines are recommended to undergo a PSMA (Prostate-Specific Membrane Antigen) PET, then the PSMA PET must show localized disease.
6. Patients must have preferably undergone a standard of care pretreatment MRI fusion biopsy\* to identify visible intraprostatic lesions and confirm the absence of regional or distant metastatic disease, with criteria as follows:
* Ability to undergo an MRI fusion biopsy;
* Prostate size \<100 cc on any diagnostic MRI;
* Presence of a visible prostatic lesion:
* PIRADS (Prostate Imaging-Reporting and Data System) 4+ lesion, and/or
* PIRADS 3 lesion with evidence of grade group 2-3
* Less than or equal to 4 lesions in total allowed;
* Lesion may contact the capsular edge, "possible" extracapsular extension (ECE) permitted; \*MRI fusion biopsy is preferred but if the positive core is in the same region as the target on the MRI based on a systemic biopsy, the patient can be included.
7. Genitourinary function with a baseline score ≤20 as defined by any pre-treatment IPSS questionnaire.
8. Patients are mandated to get a fiducial placement. Optional proper rectal spacer placement is recommended as determined by the treating radiation oncologist based upon whether there is overt rectal wall invasion from the hydrogel spacer or if there is minimal to no separation of the prostate-rectal interface measured at the prostate mid-gland.
9. Patients with a life expectancy of greater than 5 years as assessment by the investigator. Life expectancy can be estimated using any 1 of the following tools:
* The Social Security Administration tables: https://www.ssa.gov/OACT/STATS/table4c6.html
* The WHO's Life Tables by country: https://apps.who.int/gho/data/view.main.60000?lang=en
* The Memorial Sloan Kettering Male Life Expectancy tool: https://www.mskcc.org/nomograms/prostate
* If using a life expectancy table, life expectancy should be adjusted using the clinician's assessment of overall health as follows: best quartile of health - add 50%; worst quartile of health - subtract 50%; and middle two quartiles of health - no adjustment. See the NCCN Prostate Cancer Guidelines for more information.
10. Patients who agree to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agree to refrain from donating sperm, as defined below:
* With a female partner of childbearing potential who is not pregnant, men who are not surgically sterile must remain abstinent or use a condom plus an additional contraceptive method, which together result in a failure rate of \< 1% per year, during the treatment period and for 1 year after treatment per local and institutional guidelines. Men must refrain from donating sperm during this same period.
* With a pregnant female partner, men must remain abstinent or use a condom during the treatment period per local and institutional guidelines to avoid potential exposure to the embryo.
* The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or post-ovulation methods) and withdrawal are not adequate methods of contraception.
11. Patients who are able to give informed consent.
Exclusion Criteria:
1. Patients with evidence of disease Grade Group 4 (GG4) or higher.
2. Patients with PSA \>20 ng/mL.
3. Patients with evidence of clinical stage T3a+ or gross extracapsular extension on the diagnostic MRI.
4. Patients who received prior or concurrent androgen deprivation therapy for prostate cancer.
5. Patients with more than 4 disease foci identifiable on MRI.
6. Patients with evidence of metastatic disease on imaging (e.g., bone scan, PSMA PET scan, or MRI/CT scan).
7. Patients with ineligibility to undergo an MRI due to:
* The presence of a cardiac pacemaker, defibrillator, or other implanted metallic or electronic device which is considered MRI unsafe;
* Severe claustrophobia;
* Inability to lie flat for the duration of the study;
* Metallic implant or device in the pelvis that might distort the local magnetic field and compromise quality of MRI;
* Any other reason as determined by the investigator or treating physician.
8. Patients with an I-PSS score \>20 as defined by any pre-treatment IPSS questionnaire.
9. Patients with a prior history of transurethral resection of the prostate, TURP, Urolift, or other similar trans-urethral LUTS management procedure within the last 6 months.
10. Patients with a prior history of severe urethral stricture.
11. Patients with a prior history of pelvic irradiation.
12. Patients unable to meet dosimetric constraints
13. Patients with a prior history of non-cutaneous solid malignancy within the last 5 years.
14. Patients with a history of active and uncontrolled inflammatory bowel disease.
15. Patients who are unable to comply with follow-up visits and treatment plans.
