• Patients with adenocarcinoma of the prostate that in the opinion of the urologist could be resected after response to systemic therapy. Ductal adenocarcinoma is permitted.

• Patients must be regarded as acceptable surgical risk and confirm their intention to undergo radical prostatectomy at the end of the pre-surgical therapy.

• ECOG performance status 2 or better.

• All patients must have tumor staging and meet at least one of the following criteria:

∙ Either lymph node biopsy or lymph node dissection demonstrating lymph node metastasis by prostate cancer.

‣ Non-bulky (\<5 cm) regional pelvic or distant lymphadenopathy visualized on CT/MRI/PET scan. Lymph node biopsy confirmation will be required if \<2.0 cm or in atypical distribution\*.

‣ The 2018 AJCC staging system will be followed.

• Prior hormonal therapy (LHRH agonist/antagonist with or without first-generation antiandrogen) up to 6 weeks is permitted, provided any tumor biopsy specimen collected prior to initiation of ADT is made available for biomarker studies. If patient was started on first-generation antiandrogens, these would be discontinued prior to randomization.

• Patients must agree to tissue collection for correlative studies at the specified timepoints. At the study entry, any previously collected diagnostic tumor biopsy blocks from primary and/or metastatic tissues must be provided.

• Patients must have adequate bone marrow function defined as hemoglobin ³10 g/dL, an absolute peripheral neutrophil count (ANC) of ≥1,500/mm3 and platelet count of ≥100,000/mm3; no features suggestive of MDS/AML on peripheral blood smear; adequate hepatic function defined with a total bilirubin of ≤1.5 x upper limit of normal (ULN) (≤3 × ULN in subjects with Gilbert's disease), and AST/ALT ≤2.5 x ULN; adequate renal function defined as creatinine \<1.5 x ULN or creatinine clearance ≥30 mL/min (measured or calculated with the Cockcroft-Gault Equation).

• Medications known to lower the seizure threshold must be discontinued or substituted at least 4 weeks prior to study entry.

• Patients or their partners must be surgically sterile or must agree to use one highly method or two effective methods of contraception while receiving study treatments and for at least 4 months thereafter. The definition of effective contraception should be in agreement with local regulation and based on the judgment of the principal investigator or a designated associate.

⁃ Patients must sign the current IRB approved informed consent indicating that they are aware of the investigational nature of this study, in keeping with the policies of the institution, and willing and able to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.

⁃ All patients must have a surgical and medical oncology consult prior to signing informed consent.