Veterans Affairs Seamless Phase II/III Randomized Trial of STAndard Systemic theRapy With or Without PET-directed Local Therapy for Oligometastatic pRosTate Cancer

Surgery will be used to treat metastases.

"Radiation therapy will be used to treat metastases.~Radiation options include:~1. Stereotactic body radiotherapy (SBRT) using 1-10 fractions~2. Conventionally fractionated radiotherapy using elective nodal radiotherapy and a simultaneous integrated boost to involved nodes~The selection of the form of metastasis-directed radiotherapy for each metastasis will be determined using shared decision-making between the treating physician and the Veteran."

For Veterans who have a local recurrence in addition to oligorecurrent metastatic lesions, they will undergo salvage local therapy using brachytherapy, SBRT, surgery, cryotherapy or HIFU. The selection of modality of salvage local therapy will be determined using shared decision-making between the treating physician and Veteran.

Androgen deprivation therapy (ADT) using an LHRH agonist

ADT adding anti-androgen therapy to an LHRH agonist

ADT using an LHRH Antagonist.

Enhanced SST using chemohormonal therapy

Enhanced SST using Abiraterone + Prednisone

Enhanced SST using Abiraterone + Methylprednisolone

Enhanced SST using ADT + Apalutamide

Enhanced SST using ADT + Enzalutamide

"Veterans in ARM 1 will receive prostate-directed RT only and NO treatment to any nodal or distant metastatic sites.~Acceptable dose/fractionations include 55 Gy in 20 fractions and 36 Gy in 6 fractions.~Veterans in ARM 2 should receive prostate-directed local therapy using radiotherapy or radical prostatectomy in addition to PET-directed local therapy to metastases."