This is a single center single arm prospective pilot study investigating the safety of high dose rate (HDR) brachytherapy as monotherapy delivered in 2 fractions 3 hours apart. HDR monotherapy has been established as safe and effective in this context, however previous studies have delivered 2 fractions on separate days, or at least 6 hours apart. Clinically, this regimen, if shown to be safe and effective in future studies, has the potential to reduce operative resources and logistical stresses on brachytherapy departments.

PRIMARY OBJECTIVES:

I. To determine the safety of HDR monotherapy 13.5 Gy x 2 fractions delivered 3 hours apart in patients with low and intermediate risk prostate cancer.

SECONDARY OBJECTIVES:

I. To describe the prostate specific antigen (PSA) kinetics associated with HDR brachytherapy monotherapy 13.5 Gy x 2 fractions delivered 3 hours apart for low and intermediate risk prostate cancer.

OUTLINE:

Treatment will be administered on an outpatient basis. All treatment will be delivered over a single day. Participants will be followed for 6 months after last treatment or removal from study, or until death, whichever occurs first. Additional Follow up will be as per usual guidelines for prostate cancer, every 3 months following treatment with PSA for the first year, then every 4 months after year 2, and every 6 months after year 3 until 5 years of follow up are completed.

Inclusion Criteria:

1. Participants must have histologically or cytologically confirmed diagnosis of prostate adenocarcinoma.
2. National Comprehensive Cancer Network low to intermediate risk stratification.
3. No prior treatment for prostate cancer and no prior androgen deprivation therapy.
4. Age >=18 years.
5. Eastern Cooperative Oncology Group (ECOG) performance status <2 (Karnofsky >60%.
6. Eligible to undergo High dose rate (HDR) brachytherapy as monotherapy as determined by the treating radiation oncologist.
7. Ability to understand and the willingness to sign a written informed consent document.
8. Human immunodeficiency virus (HIV)-infected individuals on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
9. For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
10. 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.
11. 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.

Exclusion Criteria:

1. Any prior treatment for prostate cancer.
2. Any prior androgen deprivation therapy.
3. Is currently receiving any other investigational agents.
4. Abnormal pre-brachytherapy assessment raising concern for undergoing HDR brachytherapy procedure.
5. Contraindications to general anesthesia.
6. Contraindications to radiotherapy.
7. Prior cryosurgery or cryotherapy to the prostate.
8. Prior transurethral resection of the prostate within the previous 6 months.