Brief Summary: This pilot clinical trial studies the side effects of recombinant EphB4-HSA fusion protein before surgery in treating patients with transitional cell carcinoma of the bladder, prostate cancer, or kidney cancer. Recombinant EphB4-HSA fusion protein may block an enzyme needed for tumor cells to multiply and may also prevent the growth of new blood vessels that bring nutrients to the tumor. Giving recombinant EphB4-HSA fusion protein before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.

Detailed Description: PRIMARY OBJECTIVES: I. To determine the feasibility of, and adverse events associated with, treatment with soluble ephrin type-B receptor 4 (sEphB4)-human serum albumin (HSA) (recombinant EphB4-HSA fusion protein) prior to minimally invasive robotic surgery in patients with either muscle-invasive transitional cell carcinoma of the bladder; clear cell renal cell carcinoma (4 cm or greater); or prostate cancer Gleason (7 or under). SECONDARY OBJECTIVES: I. To determine tumor response to neoadjuvant sEphB4 as measured by imaging response and pathologic response. TERTIARY OBJECTIVES: I. To evaluate the expression of ephrin type-B receptor 4 (EphB4) and eph-related receptor tyrosine kinase ligand 5 (EphrinB2) in the archival tumor samples and explore potential associations with outcome. II. To bank specimens for future correlative biomarker studies based on the results of ongoing biomarkers analyses in the phase I of sEphB4-HSA as a single agent. III. To evaluate changes in deoxyribonucleic acid (DNA) methylation of the surgical specimen after being treated with sEphB4-HSA. IV. To evaluate the infiltration of immune cells into the tumor due to administering sEphB4-HSA. V. To evaluate the impact sEphB4-HSA has on vessel density on the tumor tissue. VI. To assess the applicability of using sEphB4-HSA for treating genitourinary cancers. VII. To assess the applicability of using contrast-enhanced ultrasound imaging for determining pathological complete response (pCR) rate. OUTLINE: Patients receive recombinant EphB4-HSA fusion protein intravenously (IV) over 60 minutes once weekly for 3 weeks (3 doses) in the absence of disease progression or unacceptable toxicity. Patients who agree may receive the fourth dose after an additional week as determined by the study medical oncologist. Two to four weeks after the last dose of recombinant EphB4-HSA fusion protein, patients undergo robotic-assisted radical cystectomy or robotic-assisted radical or partial nephrectomy. After completion of study treatment, patients are followed up for 30 days.