ADT De-escalation in Selected High-Risk Prostate Cancer Patients (ADaPPt Trial) a GROUQ Led PCS Study (PCS XIV)

High-risk prostate cancer is usually treated with a combination of radiation therapy and hormone therapy (ADT). Radiation destroys cancer cells, while ADT lowers testosterone, a hormone that prostate cancer cells need to grow. Together, these treatments help control the cancer. ADT is usually given for 18 to 24 months, but it can cause side effects that may affect quality of life. Some people with high-risk prostate cancer may do just as well with a shorter course of ADT. This study will identify people who are most likely to benefit from shorter treatment using imaging scans and tumor tests. It will then evaluate whether a shorter course of ADT works as well as the standard treatment while reducing long-term side effects.

Inclusion Criteria: * • Able to understand and sign informed consent form (ICF); * Males aged ≥ 18 years; * Histologically confirmed adenocarcinoma of the prostate; * Participants with high-risk prostate cancer according to either of the following: a) High-risk disease - at least one of the following: i. T3a ii. Gleason 8 or less iii. PSA ≤ 30 ng/mL iv. Gleason 9 (4+5) not more than 30% of the biopsy (e.g. a 10-needle biopsy can only have a maximum of 3 x 9 \[4+5\]); * PTEN-proficient tumor confirmed by CLIA-certified immunohistochemistry (IHC); * PSMA-PET within 90 days prior to randomization: negative for nodal or distant disease. * Candidate for definitive radiation to prostate and pelvis; * Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 or Karnofsky performance status of ≥70%; * Testosterone ≥150 ng/dL or 5 nmol/L; * Adequate hematologic, renal, liver function (Hemoglobin ≥10 g/dL, Absolute Neutrophil Count ≥1.5x10⁹/L, Platelets ≥100x10⁹/L); * Judged to be medically fit for ADT and RT; * Participants must be accessible for treatment and follow-up. Investigators must assure themselves the participants enrolled on this trial will be available for complete documentation of the treatment, adverse events, and follow-up. * Sexually active patients, unless surgically sterile, must agree to use condoms as an effective barrier method and refrain from sperm donation during the study treatment and for 3 months after the end of the study treatment. Exclusion Criteria: * • Prior local or systemic therapy for prostate cancer (e.g. ADT, chemotherapy or novel Androgen Receptor Inhibitors \[ARIs\]); * PSMA-PET positive nodal or distant metastases; * PTEN loss or equivocal by IHC (at least more than 50%); * Evidence of nodal or distant metastases on conventional imaging; * Prior pelvic radiation or prostate surgery interfering with RT (except biopsy/TURP); * Life expectancy \