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.
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.