This study is being done to determine if patients receiving personalized exercise therapy (versus those who do not receive personalized exercise therapy) have improved quality of life and physical functioning after completing their radiation therapy. Second, the study is being done to find if the quality of life changes during therapy correlate with measurements of inflammation in the blood. Third, the study is being done to see if adding exercise therapy to radiation therapy will improve survival.

In 2018, 30,000 patients were diagnosed metastatic prostate cancer in the US. Short-course radiation therapy (RT) is a mainstay of treatment for symptomatic metastases, and it stimulates an immune response against the tumor. However, RT also decreases systemic interleukin-1 receptor antagonist (IL-1Ra), placing the body in a pro-inflammatory state, and increasing fatigue and reducing quality of life (QOL). Fatigue and QOL are surrogates of the limited 2-20 month survival time. If fatigue and quality of life are improved, then toxicity and survival will follow.

Our long-term goal is to identify the potential for exercise therapy (ET) to improve RT treatment toxicities and outcomes among men diagnosed with metastatic prostate cancer metastatic to distant sites or regional lymph nodes. The mechanistic hypothesis is that adding ET training to RT decreases long-term systemic inflammation, mitigating toxicity thereby widening the therapeutic window.

Objective 1. Quantify the potential of Exercise Therapy (ET) to mitigate Radiation Treatment (RT) toxicities and physical function decline. The hypothesis is that ET mitigates patient-reported quality of life (QOL) and toxicities of RT. Our approach will be to use standardized questionnaires and assessment tools to assess QOL and physical function.

Objective 2. Characterize the immunologic mechanism by which ET mitigates RT toxicity. The hypothesis is that ET mitigates the toxicity of RT (measured in objective 1) by increasing serum interleukin-1Ra (IL-1Ra).

Objective 3. Evaluate the ability of ET to improve survival. Since physical function is a surrogate of survival, the hypothesis is that adding ET to RT will improve overall survival, measured from the date of start of radiotherapy until death.

Inclusion Criteria:

• Subjects must have lymph node positive or metastatic disease consistent with prostate cancer
• Males ≥18 years of age receiving RT
• Patient receiving 5 fractions or stereotactic body radiation therapy (SBRT)
• Patient may have received prior hormone therapy. Prior or current use of chemotherapy agents is allowed, but not necessary.
• Fluent in written and spoken English
• Must be able to provide and understand informed consent
• Must have an ECOG Performance Status (PS) of ≤ 3
• Primary attending radiation oncologist approval

Exclusion Criteria:

• Performing > 90 minutes/week of exercise therapy prior at time of enrollment
• Evidence in the medical record of an absolute contraindication for exercise
• Cardiac exclusion criteria:
• Class II, III or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system
• History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty or stenting within the past 6 months prior to the start of radiation therapy
• Uncontrolled arrhythmias; patients with rate-controlled atrial fibrillation for >1 month prior to start of radiation therapy may be eligible
• syncope
• acute myocarditis, pericarditis, or endocarditis
• acute pulmonary embolus or pulmonary infarction
• thrombosis of lower extremities
• suspected dissecting aneurysm
• pulmonary edema
• respiratory failure
• acute non-cardiopulmonary disorder that may affect exercise performance or be aggravated by exercise
• Mental impairment leading to inability to complete study requirements
• In-patient receiving radiation therapy for a radiation emergency (e.g. cord compression, Superior vena cava (SVC) syndrome, brain metastases)
• High risk of fracture or spine instability (Mirels score ≥7, SINS ≥7)
• Children (the protocol will only include men age 18 and older)

Plan to share all collected data relevant to results in publication.