Prostate Cancer is the most commonly diagnosed cancer among Veterans, comprising 30% of new cancer diagnoses in the VA. Eighty-five percent of men present with localized prostate can- cer, which is typically treated with active surveillance or curative local therapy using surgery or radiation therapy. Unfortunately, twenty percent of Veterans undergoing curative local therapy will develop metastatic recurrence. These men typically receive palliative systemic hormonal therapy to control their disease. Despite this, over half of men will have cancer progression within 1-2 years and half will die within 5 years. Two diverging paradigms have been studied in recent years to improve the survival of men with recurrent metastatic prostate cancer. First, a subset of patients has oligorecurrent disease, de- fined as 1-5 sites of metastases. These patients are hypothesized to have an intermediate clini- cal state in which ablative local therapy with surgery or radiation to all metastatic sites of dis- ease (metastasis-directed therapy; MDT) can lead to durable disease control and potentially cure in select patients. Recent Phase II randomized trials have demonstrated improved long- term progression-free survival with MDT in the absence of systemic therapy. Yet, 75% of patients receiving MDT for oligorecurrent cancer develop progression in new areas, arguing that systemic therapy is needed to treat occult metastases. This is supported by data demonstrating that earlier palliative hormonal therapy is associated with improved survival. In fact, the second approach that has been studied in recent years, is whether escalating hormonal therapy by adding novel androgen receptor axis targeted agents or chemotherapy improves out- comes in men with metastatic prostate cancer. Multiple phase III randomized trials demonstrate that escalating hormonal therapy with these novel therapeutic agents improves progression-free survival and overall survival dramatically. Therefore, these agents have been integrated as an option into today’s standard systemic therapy (SST) for metastatic recurrence. Given the promise of MDT to induce long-term cancer control and the effectiveness of SST to prevent further cancer progression, there is an urgent need to determine whether adding MDT to SST improves disease outcomes further. The primary goal of our study is to determine if add- ing MDT improves disease control compared to SST alone in Veterans with oligorecurrent pros- tate cancer. We will conduct a multi-institutional phase II randomized trial comparing SST with or without MDT. Other goals of the study are to determine any differences in patterns of cancer progression, survival, quality of life, and the cost-effectiveness of each approach. We also will determine how RNA transcriptomic analysis and DNA sequencing of the primary tumor from the original prostate cancer diagnosis can help determine which Veterans benefit the most from MDT. We will also utilize the VA National Precision...