• Signed Informed Consent Form

• Age \>18 years at time of signing Informed Consent Form

• Ability to comply with the study protocol

• Histologically or cytologically confirmed proof of muscle invasive urothelial cancer. This may include any patient requiring cystectomy (or nephroureterectomy to resect tumors), including muscle invasive disease (cT2-4aN0M0). Patients with the following high-risk features who are not candidates for traditional neoadjuvant chemotherapy will be included for this trial: micropapillary, sarcomatoid and plasmacytoid features; 3-D mass on exam under anesthesia (EUA); lymphovascular invasion; hydronephrosis (unless in the opinion of the treating physician, this is not due to tumor); high grade (grade 3) tumors of the ureter, renal pelvis, or tumors in these areas with radiographic abnormality large enough to recognize as an abnormal mass by CT or MRI imaging5; direct invasion of the prostatic stroma or the vaginal wall (i.e. cT4a disease). For patients in whom eligibility is unclear, final arbitration will be determined by the Principal Investigator.

• Subjects must be considered cisplatin ineligible as per treating physician (Eastern Cooperative Oncology Group performance status (ECOG-PS) 2, creatinine clearance (CrCl) \<60 mL/min, grade \> 2 hearing loss, grade \> 2 neuropathy, or New York Heart Association (NYHA) class III heart failure. See FDA draft guidance n adjuvant therapy in bladder cancer https://www.fda.gov/media/142544/download) or have refused cisplatinbased chemotherapy as a neoadjuvant therapy.

• Tissue resected by transurethral resection of bladder tissue (TURBT) at the MD Anderson Cancer Center; if completed TURBT at the outside facility, it must be within three months and must transfer outside TURBT tumor tissues to MD Anderson for correlative research on this trial.

• Eligible for R0 resection with curative intent at the time of screening, as confirmed by the operating attending surgeon and involved medical oncologist prior to study enrollment

• Adequate pulmonary function to be eligible for surgical resection with curative intent, as assessed by PFTs performed within 6 months of planned resection and repeated at screening, if clinically indicated, including lung volumes, spirometry, and a diffusion capacity; and meeting at least one of the following criteria:

∙ Predicted postoperative (ppo) forced expiratory volume in 1 second (FEV1) and ppo diffusion capacity of the lung for carbon monoxide (DLCO) \>40%

‣ Maximal oxygen consumption (VO2max) \>15 mL/kg/min

• If either ppoFEV1 or ppoDLCO is \<40% or a pneumonectomy is planned, cardiopulmonary exercise testing must be performed and VO2max \>15 mL/kg/min.

⁃ If PFTs were performed before 6 months of planned resection or have not been previously performed, they must be performed during the screening period.

⁃ Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1

⁃ Normal life expectancy, excluding lung cancer mortality risk

⁃ Adequate hematologic and -end organ and marrow function, defined by the following laboratory test results, obtained within 14 days prior to initiation of study treatment:

• ANC \> 1.5 x 109

• /L (1500/µL) without granulocyte colony-stimulating factor support

∙ Lymphocyte count \>0.5 x 109

• /L (500/µL)

∙ Platelet count \>100 x109

• /L (100,000/µL) without transfusion

∙ Hemoglobin \>90 g/L (9 g/dL)

⁃ 1\. Patients may be transfused to meet this criterion. e. AST, ALT, and ALP \<2.5 x upper limit of normal (ULN) f. Total bilirubin \<1.5 xULN with the following exception: Patients with known Gilbert disease (\>3 xULN): who must have a baseline total bilirubin \<3.0 mg/dL g. Creatinine clearance \>45 mL/min (calculated using the Cockcroft-Gault formula) h. Serum albumin \>25 g/L (2.5 g/dL)

⁃ 14\. For patients not receiving therapeutic anticoagulation: INR and aPTT \<1.5 xULN

⁃ 15\. For patients receiving therapeutic anticoagulation: stable anticoagulant regimen

⁃ 16\. Negative HIV test at screening

⁃ 17\. Negative hepatitis B surface antigen (HBsAg) test at screening

⁃ 18\. Positive hepatitis B surface antibody (HBsAb) test at screening, or negative HBsAb at screening accompanied by either of the following:

⁃ a. Negative total hepatitis B core antibody (HBcAb) b. Positive total HBcAb test followed by quantitative hepatitis B virus (HBV) DNA\< 500 IU/mL. The HBV DNA test will be performed only for patients who have a negative HBsAg test, a negative HBsAb test, and a positive total HBcAb test. c. Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody test followed by a negative HCV RNA test at screening. The HCV RNA test will be performed only for patients who have a positive HCV antibody test.

⁃ 19\. For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception, and agreement to refrain from donating eggs, as defined below:

⁃ a. Women must remain abstinent or use contraceptive methods with a failure rate of \<1% per year during the treatment period and for up to 23 weeks after the last dose of study drugs dose. Women must refrain from donating eggs during this same period. b. A woman is considered to be of childbearing potential if she is postmenarchal, has not reached a postmenopausal state (\>12 continuous months of amenorrhea with no identified cause other than menopause), and is not permanently infertile due to surgery (i.e., removal of ovaries, fallopian tubes, and/or uterus) or another cause as determined by the investigator (e.g., Müllerian agenesis). The definition of childbearing potential may be adapted for alignment with local guidelines or regulations. c. Examples of contraceptive methods with a failure rate of \<1% per year include bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices.

⁃ d. The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not adequate methods of contraception. If required per local guidelines or regulations, locally recognized adequate methods of contraception and information about the reliability of abstinence will be described in the local Informed Consent Form. e. Women who would like to become pregnant after study treatment discontinuation should seek advice on oocyte cryopreservation prior to initiation of study treatment.

⁃ 20\. For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agreement to refrain from donating sperm, as defined below:

• With a female partner of childbearing potential, men who are not surgically sterile must remain abstinent or use a condom plus an additional contraceptive method that together result in a failure rate of \<1% per year during the treatment period, for up to 90 days after the final dose of the study drugs. Men must refrain from donating sperm during this same period.

• With a pregnant female partner, men must remain abstinent or use a condom during the treatment period for 90 days after the final dose of the study drugs to avoid exposing the embryo.

• The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not adequate methods of contraception. If required per local guidelines or regulations, locally recognized adequate methods of contraception and information about the reliability of abstinence will be described in the local Informed Consent Form.

• Men who would like to father a child after study treatment initiation should be advised regarding the conservation of sperm prior to treatment because of the possibility of irreversible infertility resulting from drugs used in this study.