Scientists hunt for clues to predict which cancer treatments work best

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

Inclusion Criteria: * History of histologically confirmed prostate cancer, or other advanced / metastatic genitourinary malignancies for cohorts R (renal cell carcinoma) and U (urothelial carcinoma). Participants without histologically confirmed cancer are eligible if both the treating physician and the study PI agree that the patient's history is unambiguously indicative of advanced prostate cancer (e.g. high Prostate-specific antigen (PSA) responsive to Androgen Deprivation Therapy in prostate cancer) * Radiographic evidence of metastatic disease amenable to image-guided or excisional biopsy of a metastatic site. Soft-tissue as well as bony metastatic lesions will be considered acceptable. Participants with locally advanced disease only (where the biopsy would be of a prostatic mass) are NOT eligible. Biopsy of newly emerging or progressive metastases is desired and preferable to the biopsy of previously existing stable lesions whenever possible. Patients without lesion amenable to biopsy are still eligible, and have the option of re-assessment for potential of metastatic tumor biopsy upon progression as outlined in the study calendar. * For participants with metastatic lesion amenable for biopsy: * Platelets \> = 75,000/microliter (μl) * Prothrombin time (PT) or international normalized ratio (INR) and activated partial thromboplastin time (aPTT) \< = 1.5 times the institutional upper limit of normal (ULN) within 14 days prior to biopsy. * Patients on warfarin, aspirin, or other anti-coagulants are eligible provided they are deemed able to tolerate discontinuation of anti-coagulation prior to the biopsy as per usual standard of care. Conversion to low molecular weight heparin prior to biopsy is permitted per local standard operating procedures, provided there is agreement regarding the procedure between the treating physician, the interventional radiologist and the PI. * Participants with significant congenital or acquired bleeding disorders (e.g type 3 von Wildebrand's disease, acquired bleeding factor inhibitors) are not eligible. * Age \> 18 yrs * Eastern Cooperative Oncology Group (ECOG) Performance status 0-2 * Ability to understand and the willingness to sign a written informed consent. * Progression on or following most recent systemic therapy given for: * Metastatic Renal Cell Carcinoma (RCC) or metastatic urothelial carcinoma (UC) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or for metastatic castration resistant prostate cancer (mCRPC) by Prostate Cancer Working Group 2 (PCWG2) criteria, with progression as defined by one or more of the following: 1. PSA Progression: PSA level of at least 2 nanograms (ng)/milliliter (ml) which has risen on at least 2 separate measurements, at least one week apart (for prostate cancer participants only) 2. Disease progression by RECIST v1.1 3. Bone scan progression: the appearance of \>= 2 new lesions (for prostate cancer participants only) 4. Symptomatic progression in an area of radiologically evident disease * For prostate cancer participants only, serum testosterone \< 50 ng/dL. Participants without prior bilateral orchiectomy are required to remain on Luteinizing hormone-releasing hormone (LHRH) analogue for duration of study. Participants with previously documented denovo primary small cell carcinoma of the prostate are exempt from this criterion. If serum for analysis of testosterone level has been collected but result not available by day of scheduled baseline biopsy, patient may still be eligible for study participation upon at the discretion of the Principal Investigator * Participants must possess one of the following criteria: 1. Planned treatment within 42 days following baseline tumor biopsy and/or research blood collection with androgen signaling inhibitor excluding enzalutamide (cohort A), immunotherapy (cohort B), radiotherapy (cohort C), investigational therapeutic (cohort D), or agent targeting the DNA repair pathway including but not limited to platinum chemotherapy or poly adenosine diphosphate-ribose polymerase (PARP) inhibition (cohort E). Therapeutic combinations are allowed and as treatment may fall into more than one category, cohort assignment will be per PI discretion. 2. Aggressive variant cancer (cohort F), defined by one or more of the following: * Presence of one or more visceral organ metastases * Serum neuron specific enolase and/or chromogranin A \>ULN * Progression by PCWG2 criteria within 12 months following initiation of primary androgen deprivation therapy (ADT) +/- chemotherapy for metastatic hormone sensitive prostate cancer * Prior histologic evidence of small cell and/or intermediate atypical carcinoma differentiation * Presence of advanced or metastatic renal cell carcinoma (Cohort R) with planned treatment with a novel agent such as a targeted agent within 42 days following baseline tumor biopsy. Therapeutic combinations are allowed and as treatment may fall into more than one category, cohort assignment will be per PI discretion * Presence of advanced or metastatic urothelial carcinoma (Cohort U) with planned treatment with a novel agent such as an Antibody Drug Conjugate (ADC) or a targeted agent within 42 days following baseline tumor biopsy. Therapeutic combinations are allowed and as treatment may fall into more than one category, cohort assignment will be per PI discretion. * Additional inclusion criteria for (cohort G): Metastatic hormone-naïve prostate cancer who are planning to start (Group 1) or currently receiving (Group 2) androgen deprivation therapy. The use of chemotherapy or other investigational agents is allowed but not required in both Group 1 and Group 2. * Group 1 (ADT naïve and on ADT \< 3 months): Participants who have not received LHRH analogue, LHRH antagonist or any anti-androgen for metastatic disease. Participants who have received ADT in the past 3 months will be included. Prior use of androgen deprivation therapy in the (neo)adjuvant, salvage, or biochemically recurrent setting is allowed provided the last day of effective androgen deprivation was more than 12 months prior to study entry. Androgen deprivation therapy must be planned to start within 28 days of baseline tumor biopsy. * Group 2 (ADT Pre-Treated with sub-optimal PSA nadir): Participants who have initiated androgen deprivation therapy (including LHRH agonists, antagonists and/or anti-androgens) for metastatic prostate cancer within 6-12 months prior to study entry who have suboptimal serum PSA nadir \> 0.2 ng/mL.