BLaStMA Phase II Randomized Trial of MRI-Guided Prostate Boosts Via Initial Lattice Stereotactic vs Daily Moderately Hypofractionated Radiotherapy - The Miami BLaStM Trial

Study start date: February 5, 2015

Eligibility Criteria: * A. Biopsy confirmed adenocarcinoma (including ductal) of the prostate. * B. T1-T3 disease based on digital rectal exam. * C. No evidence of metastasis by any clinical criteria or available radiographic tests (N0M0 by clinical or imaging criteria). * D. Gleason score 6-10. * E. Androgen deprivation therapy (ADT) is at the discretion of the treating physician; but, must be decided (none, short-term or long-term as counted from the luteinizing hormone-releasing hormone (LHRH) agonist or antagonist injection) prior to enrollment. An anti-androgen (e.g., bicalutamide at 50 mg per day po) is recommended to start prior to LHRH agonist injection (not recommended for LHRH antagonist injection) and is recommended to not be administered for more than 4 months. If ADT is planned, the following restrictions apply: * i. It may be initiated no more than 3 months prior to the signing of consent * ii. It must be started prior to the start of radiotherapy and * iii. The total length planned must be ≤ 30 months * F. Prostate-specific Antigen (PSA) ≤ 100 ng/mL within (+/-) 4 months of signing of consent. If PSA was above 100 and drops to ≤ 100 with antibiotics, this is acceptable for enrollment. * G. Subjects with T3 disease based on digital rectal exam (DRE), Gleason 8-10 or a PSA of \>15 ng/ml, should have a bone scan within (+/-) 4 months of signing of consent that is without evidence of metastasis. A questionable bone scan is acceptable if additional imaging studies (e.g., plain x-rays, CT, or MRI) do not confirm for metastasis. * H. Suspicious peripheral zone or central gland lesion on MP-MRI * i. Peripheral zone: Distinct lesion on dynamic contrast-enhanced MRI (DCE-MRI) with early enhancement and later washout (Note: contrast not required for enrollment), and/or distinct lesion on the ADC map (Value \<1000). * ii. Central gland: A suspicious central gland lesion on MP-MRI must have a distinct lesion on the apparent diffusion coefficient (ADC) map (Value \<1000) * I. No previous pelvic radiotherapy. * J. No previous history of radical/total prostatectomy (suprapubic prostatectomy is acceptable). * K. No concurrent, active malignancy, other than nonmetastatic skin cancer or early stage chronic lymphocytic leukemia (well-differentiated small cell lymphocytic lymphoma). If a prior malignancy is in remission for ≥ 5 years then the patient is eligible. * L. Ability to understand and the willingness to sign a written informed consent document. * M. Zubrod performance status ≤ 2. (Karnofsky or Eastern Cooperative Oncology Group (ECOG) performance status may be used to estimate Zubrod). * N. Willingness to fill out quality of life/psychosocial forms. * O. Age ≥ 35 and ≤ 85 years at signing of consent.