This is a tissue and blood collection protocol requiring image-guided biopsies of metastatic prostate cancer. Whenever possible, a new bone lesion or new/progressing soft tissue lesion will be chosen for biopsy as opposed to radiographically stable lesion. Patients will be enrolled in parallel into one of five patient cohorts based modality of planned or recently initiated systemic therapy, as well as disease setting: (A) Androgen signaling inhibitor, (B) Immunotherapy, (C) Chemotherapy, (D) Targeted therapy, or (E) Castration-sensitive disease. Patients in cohort E will be enrolled in one of two groups: Group 1 (treatment-naïve), and Group 2 (pre-treated) (see previous section for definition). Patients enrolled in Cohorts A-D, as well as Cohort E group 1, will undergo baseline tumor biopsy prior to initiation of next line of systemic therapy. For patients enrolled in Cohort E, group 2, patients will undergo the first tumor biopsy between 6-8 months after first dose of LHRH analogue delivered as treatment for metastatic prostate cancer.