PSMA-High: EBRT/ PSMA617/ ADT vs. EBRT/ ADT

Inclusion Criteria

• •Patient must have high-risk prostate cancer (HRPC) defined by presence of exactly one high-risk feature: cT3a OR Grade Group 4 or 5 OR PSA \> 20 ng/mL.
• •Histologic confirmation of adenocarcinoma of the prostate.
• •Patient must have localized HRPC defined by conventional imaging (no N1 disease by CT or MRI). Patients with or without intra-pelvic nodal metastases by PSMA-PET may be included as long as not enlarged \>10mm short axis by conventional CT size criteria.
• •Patients must have PSMA-PET (68Ga-PSMA-11 or 18F-DCFPyL) with prostate tumor SUVmax \> 10.
• •Patient must qualify for definitive treatment of prostate cancer including EBRT as well as ADT (up to 45 days of prior ADT is allotted).
• •Patient must be ≥ 18 years of age.
• •Patient must have a life expectancy ≥ 24 months.
• •Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
• •Adequate bone marrow reserve and organ function as demonstrated by complete blood count and chemistry panel completed within the prior 6 weeks demonstrating:
• •1. Platelet count of \>100 x109/L
• •2. White blood cell (WBC) count \> 3,000/mL
• •3. Neutrophil count of \> 1,500/mL
• •4. Hemoglobin ≥ 10 g/dL
• •5. Estimated glomerular filtration rate (eGFR) \> 50 mL/min based upon Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equation. Due to safety concerns relating to renal clearance and toxicity of 177Lu-PSMA-617, patients with estimated GFR between 50 - 60 mL/min will require a 99mTc-TPA GFR test and only patients with non-obstructive pathology will be included in the study.
• •6. Total bilirubin \< 3 x ULN (except if confirmed history of Gilbert's disease)
• •7. Serum albumin \> 30 g/L
• •8. Aspartate aminotransferase (AST) \< 3 times the ULN
• •For male patients with partners of childbearing potential, agreement to use barrier contraceptive method (condom) and to continue its use for 6 months from receiving the last dose of 177Lu-PSMA-617.
• •Patient must have the ability to understand and the willingness to sign a written informed consent document.