This study will evaluate whether a lifestyle intervention focused on weight loss, EMPOWER, reduces prostate cancer progression at 12 months among men with biochemical recurrence following local treatment for prostate cancer. Half of the men will be randomized to receive the EMPOWER intervention, while the other half will receive standard of care.

Approximately 500,000 US men are living with biochemical recurrent prostate cancer (BCR). Therapies are needed to delay the appearance of metastatic disease and need for androgen deprivation therapy (ADT), which has significant adverse side effects. Observational evidence suggests that weight loss may slow the rate of disease progression. The EMPOWER trial will use an enhanced version of a remote weight loss intervention shown to yield clinically significant weight loss to test whether weight loss reduces prostate cancer progression at 12 months. EMPOWER has the potential to provide men with BCR a "first line therapy" to slow disease progression and delay the need for ADT. Importantly, this "treatment" is without significant side effects, and can improve overall health.

Inclusion Criteria:

• Understand and voluntarily sign consent form
• Able to adhere to study protocol
• Demonstrated use of internet and email
• Access to internet at least 4 days per week
• Willingness to change diet, physical activity and weight
• Willingness to be randomized to immediate start or standard of care
• Histologically confirmed diagnosis of adenocarcinoma of the prostate with evidence of biochemical recurrence following local therapy (surgery and radiation will be allowed). Biochemical recurrence will be defined as a PSA >= 0.2 ng/mL.
• Surgically treated men must not be eligible for or decline salvage radiation. Men who recurred within 3 years of completion of salvage radiation will be included.
• Definitive therapy (surgery or radiation) should be at least 4 weeks from time of consent.
• Men who received prior hormone therapy with definitive local therapy (standard with radiation) are permitted if serum testosterone level is >150 ng/dL and hormone treatment was discontinued > 1 year from time of enrollment.
• Body mass index >= 25 kg/m2
• Eastern Cooperative Oncology Group (ECOG) performance status < 2
• Willingness to return for clinical visit at 6 months, 12 months, and 24 months
• Men receiving testosterone replacement therapy will be included if they are on a stable dose with testosterone levels in the normal range.

Exclusion Criteria:

• Any clinical or radiographic evidence of metastatic disease by computed tomography (CT) of the chest, abdomen and pelvis and technetium-99 bone scintigraphy (bone scan)
• MI, stroke or ASCVD procedure within 6 months
• Serious medical condition likely to hinder accurate measurement of weight, or for which weight loss is contraindicated, or which would cause weight loss
• Unstable angina or medical conditional that would prevent routine exercise
• Prior or planned bariatric surgery
• Use of prescription weight loss medication (including off label use of medications) or over-the-counter orlistat within 6 months
• Chronic use (at least past 6 months) of medications likely to cause weight gain or prevent weight loss (e.g. corticosteroids, lithium, olanzapine, risperidone, clozapine), including androgen deprivation therapy
• Unintentional or intentional weight loss within 6 months of enrollment (≥ 5% of body weight)

De-identified individual participant data for primary and secondary outcome measures will be made available.

Starting 6 months after publication

Investigators interested in using study data to address questions beyond the scope of the project can request de-identified data from the PI in writing. The PI will provide access to de-identified data if the study goals are consistent with participant consent, and the requesting investigative team can provide the necessary assurances of proper handling of the data, including Institutional Review Board (IRB) approval and execution of a data use agreement.

The randomization scheme will be generated by the senior biostatistician, and access will be restricted for the duration of the trial. The participants and interventionists will not be blinded to study arm. The study staff involved in data collection, staff involved in laboratory measurements, and the biostatistician conducting the data analysis will be blinded to the random assignment.