This phase II trial studies how well a positron emission tomography (PET)/computed tomography (CT) scan using fluciclovine F18 compared with a PET/CT scan with 68Ga-PSMA works in planning radiation treatments and enhancing outcomes in patients with prostate adenocarcinoma. Fluciclovine F18 and 68Ga-PSMA are types of tracers, called radiotracers, that are injected and can accumulate in tumor cells to develop images of them during a PET/CT scan. It is not yet known whether giving fluciclovine F18 or 68Ga-PSMA may work better in planning radiation treatments and enhancing outcomes in patients with prostate adenocarcinoma.

PRIMARY OBJECTIVES

I. Improve the outcomes of post-prostatectomy radiotherapy prostate cancer patients via selection and treatment optimization with advanced molecular imaging with dose escalation.

II. Establish the role of advanced molecular imaging with fluciclovine F18 (fluciclovine [18F]) and gallium Ga68-labeled prostate specific membrane antigen PSMA-11 (68Ga-PSMA) PET/CT in influencing post-prostatectomy radiotherapy decision-making.

III. Establish the role of advanced molecular imaging with fluciclovine 18F or 68Ga-PSMA in altering radiotherapy treatment volumes.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive fluciclovine F18 intravenously (IV) and undergo a PET/CT over approximately 30 minutes.

ARM II: Patients receive 68Ga-PSMA IV, wait 60 minutes, then undergo a PET/CT over approximately 30 minutes.

After completion of study treatment, patients are followed up every 6 months for up to 5 years.

Inclusion Criteria:

• Adenocarcinoma of the prostate, post radical-prostatectomy
• Detectable prostate-specific antigen (PSA)
• Eastern Cooperative Oncology Group (ECOG)/Zubrod performance status of 0-2
• No definitive findings for skeletal metastasis on technetium 99-m methyl diphosphonate (MDP) or F-18 PET bone scan
• No definitive findings of systemic (extrapelvic) metastasis on CT and/or magnetic resonance (MR) scan of abdomen and pelvis
• Willingness to undergo pelvic radiotherapy

Exclusion Criteria:

• Contraindications to radiotherapy (including active inflammatory bowel disease or prior pelvic radiotherapy)

• Inability to undergo fluciclovine or Ga-PSMA PET-CT

• Definitive findings of systemic metastasis on conventional imaging or biopsy

• Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years

• Severe acute co-morbidity, defined as follows:

  • Unstable angina and/or congestive heart failure requiring hospitalization in the last 3 months
  • Transmural myocardial infarction within the last 6 months
  • Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration
  • Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration
  • Acquired immune deficiency syndrome (AIDS) based upon current Center for Disease Control (CDC) definition; note, however, that human immunodeficiency virus (HIV) testing is not required for entry into this protocol. The need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive. Protocol-specific requirements may also exclude immunocompromised patients