Principal Investigator has decided not to activate this trial.

For men with prostate cancer that involves the nearby lymph nodes (N1) standard treatment varies. Many men undergo radical prostatectomy (total removal of the prostate) along with the removal of nearby lymph nodes. Other men may opt for androgen deprivation therapy (ADT, a therapy that blocks testosterone) using the two drugs leuprolide and abiraterone - with or without radiation. This research is being done to investigate whether the use of leuprolide and abiraterone, when given in combination with a drug that blocks a molecule that senses oxygen needs by cancer cells, belzutifan, can kill cancer cells in the body prior in men who are planning on having the prostate surgically removed.

Eligible participants will receive 1 dose of leuprolide on day 1 as a subcutaneous injection and abiraterone and belzutifan as pills to take every day for 89 days. Participants will then undergo radical prostatectomy as a standard of care to treat prostate cancer approximately 2 weeks after finishing the study drugs. Participants will have PSA checked 1 year and 2 years after surgery. The list of study procedures (some of which are likely to be part of regular cancer care) will include the collection of data from medical records, imaging tests (CT/MRI/ Prostate-Specific Membrane Antigen Scan PSMA/ Positron Emission Tomography PET CT) to evaluate tumors, and blood collection.

Inclusion Criteria:

1. Willing and able to provide written informed consent.
2. Age ≥ 18 years
3. Eastern cooperative group (ECOG) performance status ≤2
4. Documented histologically confirmed adenocarcinoma of the prostate
5. Willing to undergo prostatectomy as primary treatment for localized prostate cancer
6. Regional prostate cancer (per National Comprehensive Cancer Network criteria): T1-4, N1, M0. Patients with negative conventional imaging may have regional prostate cancer defined by PSMA PET imaging.
7. Serum testosterone ≥150 ng/dL
8. Able to swallow the study drugs whole as tablets
9. Willing to take abiraterone acetate on an empty stomach (no food should be consumed at least two hours before and for one hour after dosing).
10. Willing to use a condom if having sex with a pregnant woman, or use a condom and another effective method of birth control if having sex with a woman of childbearing potential. These measures are required during and for one week after treatment with abiraterone acetate.

Exclusion Criteria:

1. Prior local therapy to treat prostate cancer (e.g. radical prostatectomy, radiation therapy, brachytherapy)

2. Prior use of enzalutamide, apalutamide, darolutamide or abiraterone acetate

3. Prior or ongoing systemic therapy for prostate cancer including, but not limited to:

   1. androgen deprivation therapy (e.g. leuprolide, goserelin, triptorelin, degarelix)
   2. Cytochrome CYP-17 inhibitors (e.g. ketoconazole)
   3. Treatment with 1st generation antiandrogen (e.g. bicalutamide) allowed if less than one month of therapy
   4. Immunotherapy (e.g. sipuleucel-T, ipilimumab)
   5. Chemotherapy (e.g. docetaxel, cabazitaxel)

4. Evidence of serious and/or unstable pre-existing medical, psychiatric, or other conditions (including laboratory abnormalities) that could interfere with patient safety or the provision of informed consent to participate in this study.

5. Any psychological, familial, sociological, or geographical condition that could potentially interfere with compliance with the study protocol and follow-up schedule.

6. Abnormal bone marrow function [absolute neutrophil count (ANC)<1500/mm3, platelet count <100,000/mm3, hemoglobin <9 g/dL]

7. Abnormal liver function (bilirubin, Aspartate transaminase (AST), Alanine Transaminase (ALT) ≥ 3 x upper limit of normal)

8. Abnormal kidney function (serum creatinine ≥ 2 x upper limit of normal)

9. Abnormal cardiac function as manifested by the New York Heart Association (NYHA) class III or IV heart failure or history of a prior myocardial infarction (MI) within the last five years before enrollment in the study.

10. History of prior cardiac arrhythmia

11. Baseline pulse oximetry of <90%