There is significant, proven use of radiation for recurrent prostate cancer after surgical resection. This treatment typically is delivered over seven and a half weeks of daily treatments, presenting a burden to patients and the health care system. Stereotactic body radiation (SBRT) is a radiation technique in which large doses are delivered over a short period of time. To date there is extremely limited evidence in SBRT for recurrent prostate cancer after surgery, with a significantly growing body of evidence for primary SBRT treatment of prostate cancer in men who opt for non-surgical upfront treatment. Additionally, advances in imaging have allowed better detection of the site of recurrence, and novel artificial intelligence aided daily-adaptive radiation therapy have allowed more precise delivery of radiation doses. This study seeks to evaluate the role of Daily-Adaptive with AI-assisted SBRT in the post operative setting utilizing Ethos Plan Adaptive technology in attempt to maintain control and minimize side effects.

This will be a two cohort Phase II single center, prospective trial, with a safety lead-in component. This design will allow an initial toxicity assessment phase of a novel radiation treatment schema that is based on other literature, but with limited evidence. There is no plan to escalate the dose. Pending assessment of the safety lead in, complete enrollment will be permitted. Each cohort will be analyzed separated for the safety lead in. There will be 7 patients in the safety lead in cohorts. The stopping point will be an incidence of 2 cases of CTCAE v5.0 Grade 3+ acute toxicity attributed to therapy within gastrointestinal or urinary domains. This generally entails symptoms significant enough to require a procedure or limit basic levels of daily activity (bathing, cooking). Actue toxicity of a comparable magnitude has been reported in the 1-5% rate in a recent meta-analysis of contemporary trials which utilized standard of care radiation. Thus two cases would represent an unacceptable increased toxicity level, and a cohort size of 7 is approximate the commonly accepted size in Phase I escalation studies to evaluate dose limiting toxicity.

Inclusion Criteria:

• Adenocarcinoma of the prostate with previous surgical resection
• Radiologically detected prostate bed OR regional nodal recurrence defined as iliac, obturator, perirectal or pre-sacral node generally encompassing below the aortic bifurcation
• Prostate bed recurrence as occurring within the region of the prostate or RTOG consensus definition of the surgical field
• At least two serum detectable PSA levels defined as >0.02 ng/dl at least 30 days apart.

Exclusion Criteria:

• Metastatic disease
• Prior radiation therapy to the pelvis region
• Inflammatory bowel disease
• Hospitalization for a gastrointestinal diagnosis in the preceeding 3 months
• Hospitalization for a urinary tract issue / diagnosis in the preceeding 3 months
• PSA >10 ng/dl at study entry,

Patients must have prostate cancer to be eligible