The purpose of this study is to find out whether combining a shorter than standard course of ADT with standard prostate brachytherapy and hypofractionated external beam radiation therapy is a safe and effective way to prevent high-risk prostate cancer from coming back and/or spreading to other parts of the body.

Inclusion Criteria:

• Pathologically-proven diagnosis of prostate adenocarcinoma

• Clinical stage T3-4 or Gleason score 8-10 or PSA >20 ng/ml

  °If radiographic T3-T4 is the only high-risk factor, it must be "consistent with" or >90% probability of having T3-T4 disease determined by the reading radiologist.

• Decipher genomic score ≤0.6

• Willing and able to provide written informed consent and Authorization for Use and Release of Health and Research Study Information (HIPAA authorization)

• Age ≥18

• KPS ≥70 or ECOG 0-2

• Estimated life expectancy >5 years

• Baseline prostate volume ≤90 cc

• Baseline IPSS ≤20

• No contraindications to ADT, brachytherapy, or pelvic external beam radiation therapy as determined by the treating radiation oncologist per standard practice

• Patients who have already started ADT consisting of bicalutamide 50 mg PO daily with leuprolide or an equivalent GnRH analogue are eligible if given for ≤ 60 days prior to registration

Exclusion Criteria:

• Regional lymph node or metastatic disease
• Prior pelvic radiation
• Prior prostate surgery (including TURP or cryosurgery)
• Prior history of inflammatory bowel disease
• Unable to undergo anesthesia or brachytherapy
• Active second malignancy or past history of malignancies diagnosed within the last 2 years that requires active therapy and/or in remission, with the exception of resected non-melanoma skin cancers, non-muscle invasive bladder cancer, stage I head and neck cancer, or stage I colorectal cancer

Prostate cancer

Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.