• 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. Discussion with PI strongly encouraged.) Retroperitoneal lymph nodes \<15 mm in the short axis will be eligible.

• Patients who are

• o 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) or

⁃ Declined cisplatin-based neoadjuvant chemotherapy, as documented in medical chart

• Availability of tumor specimen block, cell block or 30 unstained slides from diagnosis. Patients with fewer than 30 slides available may be enrolled after discussion with the Principal Investigator.Additional research biopsy is not required.

• Karnofsky performance status ≥ 70%.

• Medically appropriate candidate for radical surgery (nephroureterectomy, nephrectomy, or ureterectomy), as per treating Attending Urologic Oncologist

• Age ≥ 18 years.

• Required initial laboratory values:

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

⁃ Platelets ≥ 100 x 109 /L

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

⁃ Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 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

• If patients are HIV (+) they are eligible as long as they have: cd4 \>200, undetectable viral load and on HAART therapy.