Two-fraction HDR Monotherapy for Localized Prostate Cancer

Inclusion Criteria:

1. Participants must have histologically or cytologically confirmed diagnosis of prostate adenocarcinoma.
2. National Comprehensive Cancer Network favorable intermediate risk stratification, defined as one or more intermediate risk factors such as cT2b - cT2c category, grade group 1 or 2, or PSA 10-20 ng/mL, and less than 50% of biopsy cores positive for carcinoma (i.e. for this trial, we will only include systematic biopsy cores, not targeted biopsy cores).
3. Age \>=18 years.
4. Eastern Cooperative Oncology Group (ECOG) performance status \<2 (Karnofsky \>60%).
5. Eligible to undergo High dose rate (HDR) brachytherapy as monotherapy as determined by the treating radiation oncologist.
6. Ability to understand and the willingness to sign a written informed consent document.
7. Human immunodeficiency virus (HIV)-infected individuals on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
8. For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
9. Individuals with a history of hepatitis C virus (HCV) infection must have been treated and cured. For individuals with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
10. Individuals with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
11. Willingness and ability to complete International Prostate Symptom Score questionnaires.

Exclusion Criteria:

1. Any prior treatment for prostate cancer.
2. Prior history of pelvic malignancy.
3. Any prior androgen deprivation therapy.
4. Is currently receiving any other investigational agents.
5. Abnormal pre-brachytherapy assessment raising concern for undergoing HDR brachytherapy procedure.
6. Contraindications to general anesthesia.
7. Contraindications to radiotherapy.
8. Prior history of pelvic radiotherapy.
9. Presence of lymph node or distant metastases.
10. Prior cryosurgery or cryotherapy to the prostate.
11. Prior transurethral resection of the prostate (TURP) or transurethral incision within the previous 6 months.
12. Estimated prostate volume \>60 cubic centimeters as determined by transrectal ultrasound or magnetic resonance imaging.
13. IPSS score of 15 or higher prior to treatment.