• Men ≥18 years of age

• Histologically documented prostatic adenocarcinoma with an NCCN risk group of high-risk or very high-risk. NCCN High Risk and Very High-Risk criteria shown below. (Network, N.C.C. (2021).

• Prostate Cancer (Version 02.2021).

• High Risk:

⁃ Has no very-high-risk features and has exactly one high-risk feature:

⁃ cT3a

⁃ Grade Group 4 or Grade Group 5

⁃ PSA \>20 ng/mL

• Very high:

⁃ Has at least one of the following:

⁃ cT3b-cT4

⁃ Primary Gleason pattern 5

⁃ 2 or 3 high-risk features

⁃ \>4 cores with Grade Group 4 or 5

• Prostate biopsy within 90 days prior to randomization is allowed for entry requirements. Prostate biopsy must be reviewed at MD Anderson Cancer Center. Patients with small cell, neuroendocrine, or transitional cell carcinomas are not eligible

• ECOG performance status (PS) grade 1

• No evidence of metastatic disease or clinically positive lymph nodes as documented by technetium99m (99mTc) bone scan and by computed tomography (CT) or magnetic resonance imaging (MRI) scans. Imaging may be obtained up to 60 days prior to randomization

• Minimum prostate tumor volume of 1.5 cm3 or greater as measured on prostate MRI within 60 days prior to randomization

• Distant metastatic disease or clinically positive lymph nodes not identified by conventional imaging including by technetium-99m (99mTc) bone scan and by computed tomography (CT) or magnetic resonance imaging (MRI) scans but identified PSMA PET is allowed based on provider discretion

• PSMA expression within the primary tumor with a minimum SUVmax of the primary tumor of at least 8

• Localized or locally advanced disease deemed by the surgeon to be resectable. Patients must be appropriate candidates for and plan to undergo radical prostatectomy and pelvic lymph node dissection

⁃ No prior treatment for prostate cancer including prior surgery (excluding transurethral resection of the prostate \[TURP\]), cryoablation, pelvic lymph node dissection, radiation therapy, hormonal therapy or chemotherapy

⁃ Adequate bone marrow function documented by:

∙ Hemoglobin ≥11 g/dL

‣ Absolute neutrophil count ≥1.5 x 109/L

‣ Platelet count ≥150 x 109/L

⁃ Adequate renal function defined as creatinine \<1.5 x ULN or estimated glomerular filtration rate \>60 mL/min/1.73 m2 using BSA with CKD-EPI

⁃ Adequate hepatic function documented by:

∙ Total bilirubin ≤1.5 x ULN

‣ AST ≤2.5 x ULN

‣ ALT ≤2.5 x ULN

‣ Alkaline Phosphatase (ALP) ≤2.5 x ULN

⁃ Patients with Gilbert's syndrome do not need to meet total bilirubin requirements provided their total bilirubin is not greater than their historical level. Gilbert's syndrome must be documented appropriately as past medical history

⁃ Consents to providing whole blood samples for correlative PSMA evaluation of circulating tumor cells and extra cellular vesicles

⁃ Willing and able to comply with clinic visits and study-related procedures

⁃ Provide informed consent signed by study patient

⁃ To avoid risk of drug exposure through the ejaculate (even men with vasectomies), subjects must use a condom during sexual activity while on study drug and for 6 months following the last dose of study drug. If the subject is engaged in sexual activity with a woman of childbearing potential, a condom is required along with another effective contraceptive method consistent with local regulations regarding the use of birth control methods for subjects participating in clinical studies and their partners. Donation of sperm is not allowed while on study drug and for 3 months following the last dose of study drug.