NRG-GU009: PARALLEL PHASE III RANDOMIZED TRIALS FOR HIGHRISK PROSTATE CANCER EVALUATING DE-INTENSIFICATION FORLOWER GENOMIC RISK AND INTENSIFICATION OF CONCURRENTTHERAPY FOR HIGHER GENOMIC RISK WITH RADIATION(PREDICT-RT*)

This study is being done in subjects that have high-risk prostate cancer, a low gene risk score and with a plan to receive radiation therapy to find out if: - A shorter hormone therapy treatment is as effective at controlling the prostate cancer compared to the usual 24-month hormone therapy treatment, or - If adding a new hormone therapy drug to the usual treatment increase the length of time without prostate cancer spreading as compared to the usual treatment. Depending on the group you are randomized to you could receive FDA-approved hormone therapy that you and your study doctor will decide which hormone regimen is best for you, with a couple of variations. One of the groups will receive the study drug Apalutamide that is approved by the FDA for use in prostate cancer that does not respond to hormone therapy, or for metastatic cancer that does respond to hormones, but is not yet approved for your type of prostate cancer. If you decide to take part in this study the prostate tumor tissue from your biopsy will be tested for different genes that predict the risk of your cancer spreading, this is called the Decipher risk score. The Decipher risk score is able to predict the risk of prostate cancer spreading. If you have a high Decipher Score or your disease has spread to your pelvic lymph nodes, you will get either: - The usual hormone drugs for up to 24 months plus the usual radiation therapy for 2-11 weeks depending on the type of radiation therapy given by your study doctor, or - The usual hormone drugs for up to 24 months, the usual radiation therapy, and the study drug, apalutamide, for 24 months. If you have low Decipher Score, you will get either: - The usual hormone drugs for up to 24 months plus the usual radiation therapy for 2-11 weeks depending on the type of radiation therapy given by your doctor, or - The usual hormone therapy drugs for up to 12 months plus the usual radiation therapy for 2-11 weeks depending on the type of radiation therapy given by your doctor. After you finish your study treatment, your study doctor will continue to follow your condition for at least annually and watch you for side effects.

Are you Eligible? (Inclusion Criteria)

• To be considered for this study, subjects must: 1. Have prostate cancer confirmed by pathology within 180 days 2. Have high risk disease 3. Be 18 years of age or older 4. Have no metastatic disease outside of the pelvic nodes 5. Have not have prior radical prostatectomy