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).

The standard treatment for most patients with biochemical recurrence after radical prostatectomy is salvage radiotherapy. Salvage radiotherapy delays the need for chronic, non-curative treatment, such as long-term androgen suppression, and is the only potentially curative treatment of some biochemical recurrences after prostatectomy.

Patients are recommended to undergo salvage radiotherapy to eradicate biochemical disease delivered in approximately 40 treatments over the course of 8 weeks, representing a high burden of therapy, which may be related to lower utilization of salvage radiotherapy. Modern radiotherapy for prostate cancer has been afforded many advantages including advanced image-guided radiotherapy allowing for larger dose delivery in fewer treatments and smaller margins with hypofractionated (20 treatments) and ultra-hypofractionated (5 treatments) radiotherapy.

In patients that need salvage radiotherapy, the potential advantages of hypofractionated and ultra-hypofractionated radiotherapy delivered over 20 or 5 treatments are: 1) increased convenience to patients because of fewer treatment days, 2) reduced costs to patients because of reduced travel expenses and copays, 3) improved resource utilization for physicians because of the fewer number of treatments per patient and consequently 4) reduced cost to society. In prostate cancer specifically, hypofractionated and ultra-hypofractionated radiotherapy has the added potential of not increasing toxicity with shorter treatment times.

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.