• Patients must have a diagnosis of high-grade upper tract (renal pelvis and/or ureter) urothelial carcinoma proven by biopsy or cytology within 60 days prior to registration with the following (cT1-4 N0-1 M0): a. Upper urinary tract mass on cross-sectional imaging or Tumor directly visualized during upper urinary tract endoscopy before referral to medical oncology. b. No regional lymph node metastasis or a single regional lymph node metastasis.

• Patients must not have any component of small cell carcinoma. Other variant histologic types are permitted provided the predominant (≥50%) subtype is urothelial carcinoma.

• Patients must be considered to be a candidate for definitive surgery (nephroureterectomy or distal ureterectomy) with curative intent by the treating urologist. Lymph node dissection is strongly encouraged but its scope and determination will be at the discretion of the treating urologist. Details of the surgery such as bladder cuff removal are left to the discretion of the treating urologist. Robotic or open approaches are allowed.

• Patients must be eligible for cisplatin. Cisplatin eligibility is defined as meeting all of the following criteria: a. Creatinine clearance ≥ 45 mL/min calculated by Cockcroft-Gault equation (using actual body weight) or measured by 24-hour urine collection. b. Absence of Grade ≥ 2 peripheral neuropathy. c. Absence of New York Heart Association Class III or higher heart failure.

• Prior local endoscopic therapy for upper tract urothelial cancer is permitted if completed at least 6 months prior to the initiation of study treatment and if all toxicities from such therapy have improved to grade 1 or resolved.

• Prior uro-oncologic history: a. History of or active non-invasive carcinoma or carcinoma in situ of the bladder/urethra or upper tract is allowed. b. Patients may have received prior intravesical chemotherapy or immunotherapy such as BCG. c. Prior neoadjuvant or adjuvant chemotherapy or antibody-drug conjugate for bladder cancer or invasive contralateral upper tract cancer is allowed but must have been completed ≥ 1 year prior to study registration.

• Patients must be age ≥ 18 on the date of registration.

• ECOG Performance Status 0-1.

• Criteria for patients with hepatitis B or C are listed below. Hepatitis B and C screening tests are not required unless there is a known history of HBV or HCV infection or as mandated by local healthy authority. Hepatitis B positive subjects • Participants who are HBsAg positive are eligible if they have received HBV antiviral therapy for at least 4 weeks and have undetectable HBV viral load prior to enrollment. • Participants should remain on anti-viral therapy throughout study intervention and follow local guidelines for HBV anti-viral therapy post completion of study intervention. Participants with history of HCV infection are eligible if HCV viral load is undetectable at screening. • Participants must have completed curative anti-viral therapy at least 4 weeks prior to enrollment.

• Patients must have adequate organ and bone marrow function as defined in Table 1. Specimens must be collected within 14 business days prior to start of study enrollment.

• Women and men of reproductive potential must agree to use an effective contraceptive method during treatment and for 4 months after the last dose of study drug. See Section 16.3, Appendix 3. Men must also refrain from donating sperm during this period.

• Women of reproductive potential must have a negative pregnancy test within 14 days prior to registration and are not breastfeeding.

• Patients must not have any other medical condition(s) that make(s) their participation in the study unadvisable in the opinion of the treating oncologist.

• All patients must be informed of the investigational nature of this study. The patient must have the ability to understand and the willingness to sign a written informed consent document. Patients with impaired decision-making capacity who have a legally authorized representative or caregiver and/or family member available will also be considered eligible.