• Histologically confirmed diagnosis of urothelial carcinoma of the bladder. Variant histology is acceptable if there is a predominant urothelial component.

• For MUSCLE-INVASIVE UROTHELIAL CANCER OF THE BLADDER (Cohorts 1 - 3):

• ° Cystoscopically and radiographically confirmed cT2-4a cN0 cM0 disease. Patients with cT4a disease invading into the prostatic stroma with no cystoscopic confirmation of muscle invasion are eligible.

• For UROTHELIAL CARCINOMA OF THE UPPER URINARY TRACT (URETER OR RENAL PELVIS) (Cohort U):

• °Histologically confirmed high grade urothelial carcinoma of the upper tract and/or radiographically visible tumor stage T2-T4a N0/x M0 disease with positive selective urinary cytology. Hydronephrosis associated with tumor on imaging or biopsy will be considered invasive by definition. (Variant histology is acceptable if there is a predominant urothelial component)

• Patients ineligible for cisplatin based on any of the following criteria:

‣ Estimated or calculated creatinine clearance ≥ 30ml/min but \< 60 ml/min

⁃ Grade 2 or above audiometric hearing loss (per CTCAE v4.0)

⁃ Grade 2 or above peripheral neuropathy (per CTCAE v4.0)

• Availability of tumor specimen block or 30 unstained slides from diagnosis of muscle-invasive disease. Patients with fewer than 30 slides available may be enrolled after discussion with the Principal Investigator.

• Karnofsky performance status ≥ 70%.

• Medically appropriate candidate for radical cystectomy, as per MSK Attending Urologic Oncologist

• Age ≥ 18 years.

• Required initial laboratory values:

‣ Absolute neutrophil count ≥ 1.5 x 10\^9/L

⁃ Platelets ≥ 100 x 10\^9/L

⁃ Bilirubin ≤1.5 times the upper limit of normal (x ULN)

⁃ Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3 x ULN

⁃ PTT/PT ≤1.5 x ULN or INR \< 1.7 x ULN for patients who are not receiving therapeutic anticoagulation. Patients receiving therapeutic anticoagulation should be on a stable dose.