A Study Testing if Patients With Advanced Prostate Cancer Who Are Responding Well to Combination Treatment Can Safely Reduce Their Medication to a Single Hormone Therapy, Compared to Continuing Their Current Drugs

The goal of this randomized comparative study (a study where participants are placed into groups by chance) is to find out if reducing treatment to androgen deprivation therapy (ADT)-a treatment that lowers testosterone-by itself works just as well as continuing the original combination of drugs. This study involves adult men with metastatic hormone-sensitive prostate cancer (prostate cancer that has spread to other parts of the body but still responds to hormone treatments) who have responded very well after 6 to 7 months of their initial two-drug or three-drug treatment. The main questions it aims to answer are: 1. Does reducing treatment to ADT alone work as well as the combination treatment at keeping the cancer from growing on imaging scans after 18 months, also known as radiographic progression-free survival (rPFS)? 2. Does reducing treatment to ADT alone work as well as the combination treatment at preventing a rise in prostate-specific antigen (PSA), known as PSA progression-free survival (PSA-PFS)? Researchers will compare a continuation group, which continues their initial two-drug or three-drug treatment, to a reduced-treatment group, which stops taking the androgen receptor pathway inhibitor (ARPI)-a drug that blocks the effects of hormones on cancer cells. Researchers want to see if reducing the treatment safely controls the cancer while lowering drug side effects and financial costs. Participants will: 1. Complete a 6- to 7-month initial period receiving a two-drug or three-drug treatment chosen by their doctor. 2. Have blood tests for PSA and testosterone, and undergo a specialized imaging scan called a prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) scan, to confirm the treatment is working very well before being assigned to a study group. 3. Stop taking the ARPI drug if assigned to the reduced-treatment group, or continue their current medications if assigned to the continuation group. 4. Go to check-up visits every 3 months for the first 24 months to complete physical exams, blood tests, and quality-of-life surveys. 5. Have a PSMA PET/CT scan every 6 months after being put into a group to check if the cancer has grown.