This is a Phase I/II trial evaluating the effectiveness of adding neoadjuvant HDR-B prior to RALP for HR-PCa patients with selective AAB for decipher high risk or pathologically node positive patients.

Patients with newly diagnosed, histologically confirmed, non-metastatic, HR-PCa who are scheduled to receive RALP will be eligible to participate in the study.

Approximately, 29 cancer patients will be enrolled. Patients will receive a single fraction of HDR-B (15Gy) 4-8 weeks prior to RALP.

Patients with HR-PCa who are in the upper tercile of Decipher genomic risk (≥0.85) or have pathologically node-positive disease after lymph node dissection will receive 3 months of adjuvant AAB beginning two months post-RALP, as this is SOC for this type of patient. Node positive patients will also receive adjuvant pelvic radiation as this is SOC for this type of patient.

The primary objectives of the study will be to assess the feasibility and safety of adding HDR-B prior to RALP for patients with newly diagnosed HR-PCa and to measure per-protocol treatment compliance.

Patients will be on the study for a total of up to 27 months, including 2-3 months on active study intervention (HDR-B with RALP 4-8 weeks post HDR-B) and potentially an additional 3 months (AAB).

Study follow-ups will be performed per-protocol for up to 2 years after surgery.

Inclusion Criteria:

1. Subjects must have biopsy-confirmed adenocarcinoma of the prostate.

2. Subjects must have a negative bone scan and CT scan or PSMA-PET for nodal or metastatic disease.

3. Subjects must have one of the following risk factors:

   • PSA ≥20 and/or
   • Gleason score ≥8 and/or
   • Clinical or radiographic stage ≥T3a per AJCC (American Joint Committee on Cancer) 8th Edition Staging Manual and/or
   • At least two out of four of the following: PSA (Prostate Specific Antigen) 10-19.9, GS (Gleason Score) = 4+3, clinical stage = T2b/T2c, ≥50% positive biopsy cores.

4. Subjects must freely sign informed consent to enroll in the study.

5. Subjects must be medically fit to undergo surgery and HDR-B as determined by the PI.

6. Age ≥ 40

7. ECOG Performance Status (performance status is an attempt to quantify cancer patients' general well-being and activities of daily life, scores range from 0 to 5 where 0 represents perfect health and 5 represents death): 0-1.

8. No prior invasive malignancy in the past 3-years, except non-melanomatous skin cancer unless disease free for a minimum of 2 years. Carcinoma in-situ of the bladder or head and neck region is permissible.

9. Subjects must not have had prior androgen deprivation therapy in the past 6 months.

Exclusion Criteria:

1. Metastatic disease as demonstrated by bone scan, CT scan, MRI of the pelvis, or PSMA-PET.

2. Declared high-risk for anesthesia by attending cardiologist, or other physician.

3. History of prior pelvic radiation therapy.

4. Prostate gland >70 cc as assessed by MRI or TRUS.

5. Baseline IPSS >15 with medical optimization.

6. History of androgen deprivation therapy within the past 6 months (except finasteride if discontinued > 3 mo. prior to enrollment).

7. Unwilling or unable to comply with the study protocol.

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Males