Using PET scans to guide radiation therapy for metastatic prostate cancer

Inclusion Criteria:

* Patients must have metastatic prostate cancer on conventional imaging (CT scan, MRI, and/or bone scan).

  * Note; Patients who had metastatic disease on conventional imaging prior to beginning ADT, but which has now resolved, are still eligible if they meet remaining eligibility criteria
* Patients must be ≥ 18 years of age at the time of informed consent.
* Patients must exhibit an Eastern Cooperative Oncology Group (ECOG) performance status of 0-3.
* Planned treatment requirements:

  * Cohort 1

    * Patients must have mHSPC and be planning therapy with cytotoxic therapy, with or without an androgen receptor (AR) pathway inhibitor (ARPI), to be eligible for Cohort 1. Patients may also enroll if they are currently receiving or have completed cytotoxic therapy, if they are within 26 weeks +/- 4 weeks (30 weeks) of starting cytotoxic therapy and 26 weeks +/- 26 weeks (one year) of starting ADT.

      * Note:

        * Typically cytotoxic therapy means docetaxel. Patients planning other cytotoxic therapy (e.g. cabazitaxel) should discuss this with the study principal investigator (PI).
        * If a patient registers as part of cohort 1 but ends up not receiving any cytotoxic therapy, the patient may be switched to cohort 2. This must be discussed with the study PI. If the patient received at least one cycle of cytotoxic therapy, they would remain in cohort 1.
        * Patients will continue their standard of care treatment while on study (plus MDRT if they are on Arm 1A). Change in standard of care therapy will be allowed for toxicity or for de-escalation, and the patient will remain on study. Change in therapy for progression is considered a progression event.
  * Cohort 2

    * Patients must have mHSPC and be planning therapy with androgen deprivation therapy (ADT), with or without an ARPI, and not planning cytotoxic therapy, to be eligible for Cohort 2. Patients may also enroll if they are within 26 weeks +/- 4 weeks (30 weeks) of starting an AR pathway inhibitor and 26 weeks +/- 26 weeks (one year) of starting ADT.

      * Note:

        * If patients register as part of cohort 2 but end up receiving one or more cycles of cytotoxic therapy, they may be switched to cohort 1. This must be discussed with the study PI.
        * Patients will continue their standard of care treatment while on study (plus MDRT if they are on Arm 2A). If they switch therapy because of progression, they will be considered to have progressed.
        * Patients can be enrolled anytime within the initial \~6 month standard of care time period, though early enrollment is preferred. Screening can take place prior to starting standard of care (SOC) therapy or during standard of care therapy, as long as they are within 30 weeks of starting therapy.
* Leukocytes (WBC) ≥ 2,500/mcL (growth factor use allowed) (obtained prior to registration).
* Absolute neutrophil count (ANC) ≥ 1,500/mcL (growth factor use allowed) (obtained prior to registration).
* Platelets (PLT) ≥ 80,000/mcL (transfusions allowed) (obtained prior to registration).
* Patient must be able to lie flat and still for approximately 15-20 minutes AND able to tolerate FDG-PET/CT radiographical imaging and radiation treatment planning and delivery.
* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the endpoints for this study, in the opinion of the treating investigator, are eligible.

  * Note; Patients are ineligible if another known malignancy makes it difficult to interpret if FDG-avid lesions represent prostate cancer, or if the malignancy is expected to interfere with patients receiving standard therapy for prostate cancer for 2 years from study enrollment.
* Patients must have a life expectancy of at least 6 months, in the opinion of the treating investigator.
* Patients must have the ability to understand and the willingness to sign a written informed consent document prior to registration.

  * Note: Patients with impaired decision-making capacity (IDMC) who have a legally authorized representative (LAR) or caregiver and/or family member available will also be considered eligible.

Exclusion Criteria:

* Patients with prostate cancer that is castration resistant, which is defined as two consecutive rising PSA values despite testosterone level \< 50 ng/dL.
* Patients who started androgen deprivation therapy (ADT) more than 26 weeks +/- 26 weeks (1 year) prior to enrollment.

  * Note: ADT is defined as luteinizing hormone-releasing hormone (LHRH) agonist (e.g. leuprolide, goserelin) or antagonist (e.g. degarelix, relugolix) or surgical castration. Bicalutamide 50 mg daily does not count as ADT.
  * Note: Patients will not be excluded if they were previously on intermittent therapy, as long as the current "on" period started within one year of enrollment.
* Patients who started intensification of therapy beyond ADT (e.g., AR pathway inhibitor, cytotoxic therapy) more than 26 weeks +/- 4 weeks (30 weeks) prior to registration.

  * Note: First generation antiandrogens (bicalutamide) are not considered intensification of therapy beyond ADT.
* Subjects with a known allergy to contrast material and/or contraindication to FDG-PET

  * Note: Contrast allergies: Patients with a known allergy to imaging contrast agent(s) are eligible, provided prior reactions have not been severe, and the patient is willing and able to receive pre-medications and/or supportive care according to institutional standard practice (e.g., corticosteroids, antihistamines, etc.) to manage reactions adequately.
* Patients who are enrolled in another therapeutic clinical trial that would preclude them from participating in this trial.