Randomized Phase II Trial of Salvage Radiotherapy for Prostate Cancer In 4 Weeks v. 2 Weeks

The purpose of this study is to compare urinary and bowel side effects of hypofractionated radiotherapy in 20 treatments (4 weeks) to ultra-hypofractionated radiotherapy in 5 treatments (2 weeks) for prostate cancer that has returned after prostatectomy. The investigators are also interested in looking at time to progression and the quality of life (health scores).

Inclusion Criteria: * Men aged 18 and older with histologically confirmed prostate cancer after prostatectomy with detectable PSA. PSA does not need to be detectable for men with pathologically node positive disease. * KPS \>=70 * Patient with no evidence of distant metastatic disease on PET/CT/MRI or bone scan \< 9 months prior to enrollment. Patients with positive pelvic lymph nodes are eligible. * Ability to receive MRI-guided radiotherapy. * Equivocal evidence of metastatic disease outside the pelvis on standard imaging requires documented negative biopsy. * Ability to complete the Expanded Prostate Cancer Index Composite (EPIC) questionnaire. Exclusion Criteria: * Prior history of receiving pelvic radiotherapy. * Patient with inflammatory bowel disease. * Patients with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of ultra-hypofractionated radiotherapy. * History of bladder neck or urethral stricture.