Abi/Pred + ADT vs ADT in PSMA-Positive, Conventionally Node-Negative Prostate Cancer

Inclusion Criteria:

1. Histopathologically proven diagnosis of local prostate cancer. Biopsies will be confirmed by UNMC pathology review if collected outside our institution.
2. Targetable PSMA-avid pelvic lymph node measuring \<1cm in short axis diameter.
3. No prior definitive treatment or intervention received.
4. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 within 14 days prior to registration.
5. Age ≥ 30 years.
6. Patient must be able to provide study-specific informed consent prior to study entry.
7. Patient must be able to swallow medications.

Exclusion Criteria:

1. Evidence of distant metastatic disease outside the pelvic lymph nodes (including osseous pelvic disease).
2. Presence of any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule, including alcohol dependence or drug abuse.
3. Relative or absolute contraindications to radiation therapy as determined by the treating physician. These include, but are not limited to, inflammatory bowel disease, connective tissue disorders (systemic lupus erythematosus, scleroderma, etc.), and genetic disorders that risk increased sensitivity to radiation therapy.
4. Severe, active co-morbidity, defined as follows:

   1. Unstable angina and/or congestive heart failure requiring hospitalization within the last 3 months prior to registration.
   2. Congestive heart failure (NYHA functional capacity class II or greater).
   3. Transmural myocardial infarction within the last 3 months prior to registration.
   4. History of stroke or transient ischemic attack within 3 months prior to registration.
   5. Currently uncontrolled diabetes mellitus.
   6. Ongoing arrhythmias of Grade \>2 \[National Cancer Institute's Common Toxicity Criteria for Adverse Events (CTCAE), version 5.03\]; chronic stable atrial fibrillation on stable anticoagulant therapy is allowed.
   7. Thromboembolic events (e.g., deep vein thrombosis, pulmonary embolism) in the past month.
   8. Significant vascular disease (e.g., aortic aneurysm, history of aortic dissection) or clinically significant peripheral vascular disease.
   9. Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration.
   10. Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration.
   11. Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects.
   12. Acquired Immune Deficiency Syndrome (AIDS) based upon the current Centers for Disease Control and Prevention definition that is being treated with contraindicated medications, including but not limited to Atazanavir, Saquinavir, Ritonavir, Indinavir, or Nelfinavir. Note, however, that 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.
   13. Uncontrolled seizures or seizures in the past 3 months. Patients can enroll if their seizures have been well-controlled for \>3 months on antiseizure medications.
   14. Gastrointestinal bleeding or any other hemorrhage/bleeding event CTCAE version 5 grade 3 or greater within 30 days prior to registration.
   15. History of a non-healing wound, ulcer, or bone fracture within 90 days (3 months) prior to registration.
   16. Total bilirubin ≥1.5X upper limit of normal (ULN) \[except for subjects with Gilbert's disease, in which case total bilirubin not to exceed 10X ULN\], alanine (ALT) and aspartate (AST) aminotransferase \>= 2.5X ULN.