Inclusion Criteria:
* Age: Must be 18 years or older.
* Consent: Able to understand and provide signed informed consent that complies with Institutional Review Board (IRB) or Independent Ethics Committee (IEC) guidelines.
* Diagnosis: Histologically confirmed prostate adenocarcinoma (unless a local pathologist's report shows consistent findings).
* Performance Status: Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
* Life Expectancy: Must have a life expectancy of at least 10 years.
* Germline Testing: Must have undergone germline testing at the time of initial diagnosis (and at recurrence, if applicable).
* Metastasis: No evidence of soft tissue disease metastasis (visceral or lymph nodes) on CT/MRI scan.
* Autoimmune Disease: No active or organ-threatening autoimmune disease.
* High-Risk Prostate Cancer: Must have high-risk or very high-risk prostate cancer according to 2024 NCCN guidelines (PSA \>20 ng/mL, or Gleason Grade Group ≥4, or ≥cT3a).
* Adequate Hematologic and Organ Function: Must meet specific criteria for absolute neutrophil count (ANC), lymphocyte count, platelet count, hemoglobin, INR or aPTT, AST, ALT, and alkaline phosphatase levels. Certain exceptions are made for participants with liver or bone metastases.
* Ability to Attend Visits: Must be able to attend required study visits and return for adequate follow-up.
* Contraception: If male and not surgically sterile, must agree to use effective contraception for up to 7 months after treatment.
Exclusion Criteria:
* Prior Prostate Treatments: Prior surgical, cryotherapy, or high-intensity focused ultrasound treatment for prostate cancer; prior orchiectomy or hormonal therapy (GnRH agonists, NSAA).
* Prior Anti-Androgen Therapy: Prior treatment with first-generation or second-generation androgen receptor (AR) inhibitors (e.g., bicalutamide, flutamide, nilutamide, cyproterone acetate; enzalutamide, apalutamide, or darolutamide).
* Organ Transplantation: Receipt of any organ transplantation (excluding those that don't require immunosuppression, like corneal or hair transplants).
* Corticosteroid Use: Chronic systemic corticosteroid administration (\>14 days within 28 days before treatment initiation) except for topical, inhaled, or nasal corticosteroids.
* Active Autoimmune Disease: Active autoimmune disease (e.g., Addison's disease, Hashimoto's thyroiditis, systemic lupus erythematosus, Sjogren's syndrome, scleroderma, myasthenia gravis, Goodpasture syndrome, or active Graves' disease). Exceptions are made for those with a history of autoimmune disease that did not require systemic immunosuppression and does not threaten vital organ function.
* Medications Affecting Urinary Symptoms or PSA: Use of medications for urinary symptoms (5-alpha reductase inhibitors, alternative medications known to alter PSA levels) within 28 days prior to study initiation.
* Recent Major Surgery or Systemic Therapy: Major surgery or systemic therapy (including investigational therapies) within 28 days prior to study initiation.
* Allergic Reactions: History of allergic reactions to compounds with similar chemical or biological composition to the study drugs.
* Significant Cardiovascular or Cerebrovascular Disease: Clinically significant cardiovascular/cerebrovascular disease (e.g., stroke, myocardial infarction, unstable angina, congestive heart failure, serious cardiac arrhythmia, or uncontrolled hypertension) within six months prior to the first planned dose of study drugs.
* Intercurrent Medical Illness: Serious intercurrent medical illness that would interfere with participation.
* Infections: Active HIV, hepatitis B or C infection.
* Live Attenuated Vaccines: Administration of a live, attenuated vaccine within three weeks before study entry or anticipation that such a vaccine will be required during the study.
* Inability to Comply: The investigator deems the participant unable or unwilling to comply with study requirements.
