Neoadjuvant Lu-177-PSMA-617 in Patients With High Risk Localized Prostate Cancer Undergoing Radical Prostatectomy

Inclusion Criteria: * Patients age 18 or older. * Patients with histologically confirmed adenocarcinoma of the prostate. * Patients with high-risk disease defined as a preoperative prostate biopsy of Gleason Score 8 (GS8) (Grade group 4 \[GG4\]) or higher. Men with evidence of lymph node involvement at or below the bifurcation of the common iliac arteries (cN1) on PET-CT 68Ga-PSMA-11 are eligible. * Pre-operative, pre-treatment PSMA scan with high expression in prostate confirmed by PET/CT 68Ga-PSMA-11 (greater than liver). Patients must not have any other PET FDG-positive sites outside the prostate. * Patients who are able and willing to undergo surgery. * Patients with a life expectancy of greater than 10 years. Life expectancy can be estimated using any 1 of the following tools: * The Social Security Administration tables: https://www.ssa.gov/OACT/STATS/table4c6.html * The WHO's Life Tables by country: https://apps.who.int/gho/data/view.main.60000?lang=en * The Memorial Sloan Kettering Male Life Expectancy tool: https://www.mskcc.org/nomograms/prostate * If using a life expectancy table, life expectancy should be adjusted using the clinician's assessment of overall health as follows: best quartile of health - add 50%; worst quartile of health - subtract 50%; and middle two quartiles of health - no adjustment. See the NCCN Prostate Cancer Guidelines for more information. * Patients with an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2. * Patients who agree to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agree to refrain from donating sperm, as defined below: * With a female partner of childbearing potential who is not pregnant, men who are not surgically sterile must remain abstinent or use a condom plus an additional contraceptive method that together result in a failure rate of \< 1% per year during the treatment period and for 14 weeks after the final dose of study treatment. Men must refrain from donating sperm during this same period. * With a pregnant female partner, men must remain abstinent or use a condom during the treatment period and for 14 weeks after the final dose of study treatment to avoid potential exposure to the embryo. * The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or post-ovulation methods) and withdrawal are not adequate methods of contraception. * Patients who are able to comply with follow-up visits and treatment plans. * Patients who are able to give informed consent. Exclusion Criteria: * Patients with a prior history of prostate cancer treatment. * Patients with previous treatment with PSMA-targeted radioligand therapy or any of the following within 6 months of enrollment confirmation: Strontium-89, Samarium-153, Rhenium-186, Rhenium-188, Radium-223 or hemi-body irradiation. * Patients with distant disease (outside of local lymph nodes). * Significant bone marrow impairment defined by leukocytes \<3,000/mcL, absolute neutrophil count (ANC) \<1,500/mcL, and platelet count lower than 70,000/mcL. * Significant liver function impairment defined by total bilirubin higher than 1.5 times the upper limit of normal (ULN), andASL/ALT higher than 3 times the ULN. * Impaired kidney function defined by glomerular filtration rate (GFR) lower than 40 mL/min, or concomitant use of nephrotoxic drugs. Kidney function based on eGFR by Modification of Diet in Renal Disease (MDRD) equation: * Normal renal function: participants with eGFR 90 mL/min * Moderate renal impairment: participants with eGFR 30 to 59 mL/min * Severe renal impairment: participants with eGFR 15 to 29 mL/min * Patients with significant comorbidities that would make them poor candidates for surgery. * Patients with evidence of metastatic disease (enlarged lymph nodes, distant metastatic sites, visceral or bone metastases, etc.). * Patients with a history of radiation or hormone therapy to the prostate. * Patients with a history of bleeding disorders or who are taking anticoagulant therapy. * Patients with active infections or other contraindications for surgery. * Patients who are unable or unwilling to give informed consent. * Patients who are unable to comply with follow-up visits and treatment plans