This trial studies the side effects and how well high-dose brachytherapy works in treating patients with prostate cancer that has not spread to other parts of the body. Brachytherapy is a type of radiation therapy in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near a tumor and may be a better treatment in patients with prostate cancer.

PRIMARY OBJECTIVES:

To estimate the rate of acute (within 6 months of high-dose rate [HDR] completion) grade ≥ 2 genitourinary (GU) toxicity following high-dose-rate (HDR) brachytherapy (BT) as monotherapy for newly-diagnosed prostate cancer using the National Cancer Institute's Common Terminology Criteria for Adverse Events, version 3 (CTCAE v3.0).

SECONDARY OBJECTIVES:

• Estimate the proportion of men with a prostate-specific antigen (PSA) nadir by one year (nPSA12) of < 2 ng/mL.
• Estimate the rate of freedom from biochemical failure at 5 years (FFBF).
• Evaluate patient-reported quality of life via the 32-item Expanded Prostate Cancer Index Composite (EPIC).
• Assess the cost-effectiveness of HDR BT as monotherapy for prostate cancer using the 6-item European Quality of Life 5-Dimensions (EQ-5D).
• Explore pre-treatment clinical risk factors to optimize patient selection for HDR BT as monotherapy for prostate cancer.
• Compare acute and late (> 6 months after HDR completion) GU and gastrointestinal (GI) grade ≥ 2 toxicity using CTCAE v3.0 and v4.0.
• Explore dosimetric predictors of toxicity.

Patients undergo high-dose-rate brachytherapy over 2 fractions. Patients may receive androgen deprivation therapy (ADT) comprising bicalutamide orally (PO) once daily (QD). Patients may also receive luteinizing hormone-releasing hormone (LHRH) agonist therapy comprising leuprolide acetate intramuscularly (IM) or subcutaneously (SC), goserelin acetate SC, triptorelin pamoate IM, or degarelix SC for 4 to 6 months (intermediate-risk patients receiving ADT) or 6 to 36 months (high-risk patients) at the discretion of the treating physician.

After completion of study treatment, patients are followed up at 3, 6, 9, and 12 months, and then yearly for up to 5 years.

Inclusion Criteria:

• Documented pathologic confirmation of prostate adenocarcinoma
• Clinical T-classification T1-3
• PSA < 150 ng/mL
• Gleason score 6-10
• Clinically negative lymph nodes as established by abdomino-pelvic CT. CT only for clinical classification of T3 (with contrast if renal function is acceptable; a non-contrast CT is permitted if the patient is not a candidate for contrast), magnetic resonance imaging (MRI), nodal sampling, or dissection. Patients with lymph nodes equivocal or questionable by imaging are eligible if those nodes are <1 cm in short axis diameter. [56]
• No evidence of bone metastases (M0) on bone scan, only for PSA >20 ng/mLor Gleason ≥8, (NaF PET/CT is an acceptable substitute). Equivocal bone scan findings are allowed if plain films and/or MRI are negative for definite metastases.
• American Urological Association Symptom Index (AUA SI) =< 20

Exclusion Criteria:

• Clinical T4 disease

• PSA >= 150 ng/mL

• AUA SI > 20

• History of radical prostatectomy, external beam radiotherapy (EBRT), or BT for prostate cancer

• Previous chemotherapy for any malignancy, if given within three years of registration

• History of rectal surgery

• History of rectal fistula

• History of inflammatory bowel disease

• Severe, active co-morbidity, defined as follows:

  • Unstable angina and/or congestive heart failure requiring hospitalization within the last six months
  • Transmural myocardial infarction within the last six months