• Participants must be at least 18 years of age on the day of signing informed consent. Participant (or legally acceptable representative if applicable) provides written informed consent for trial

• Participants must have either histologically or by clinical consensus (based on imaging and/or exam under anesthesia) confirmed diagnosis of muscle invasive bladder cancer (cT2-T4aN0-N1M0 or cT1-4aN1M0 clinical stage per American Joint Commission on Cancer \[AJCC\]). Patients with clinical node-positive (N1) stage are eligible provided the lymph node (LN) is confined to the true pelvis and is within the planned surgical LN dissection template; cN1 is defined as a lymph node with \>= 15 mm short axis or biopsy-positive for carcinoma

• Must have clinical non-metastatic bladder cancer (M0) determined by cross-sectional Computed tomography (CT) chest, abdomen and pelvis (CAP) or magnetic resonance imaging (MRI)

• Review of pathology by local expert genitourinary (GU) pathologist is required. Any component (%) of non-conventional urothelial (variant histology) noted on transurethral resection of bladder tumour (TURBT) is allowed, for histologic types not listed below. However, for the variant histologic types listed below, the following parameters need to be met:

‣ Squamous cell carcinoma / squamous cell features need to be pure or predominant (\>= 1 variant histologic with total non-conventional urothelial component \> 50%).

⁃ Adenocarcinoma / glandular features need to be pure or predominant (\>= 1 variant histologic total non-conventional urothelial component \> 50%).

⁃ Any % of neuroendocrine / small cell histology is excluded.

• Patients must be considered unfit for cisplatin based on the Galsky et al. criteria or refuse cisplatin despite adequate counseling in cisplatin-fit patients. Especially, for tumors containing squamous cell or glandular features, every effort should be made to discuss the benefit of neoadjuvant cisplatin-based chemotherapy shown in the S8710 trial

• Participants must be deemed eligible for radical cystectomy (RC) and pelvic lymph node dissection (PLND) by both urologist and medical oncologist

• TURBT that showed muscularis propria (or lamina propria for cT1N1 tumors) invasion should be within 12 weeks prior to beginning study therapy. Patients must have available tumor tissue from either initial or repeat TURBT, prior to starting study therapy. Archival and/or fresh tumor tissue sample of a tumor lesion (TURBT specimen) should be provided and must contain muscle invasive component, at least \>= T2 tumor (for cT2 tumors), unless clinical stage is cT1N1M0 (in that case muscle invasive component is not necessary). Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides. If submitting unstained cut slides, newly cut slides should be submitted to the testing laboratory, preferably within 14 days from the date slides are cut if possible. Patient must be willing to provide tumor tissue for research. Research samples will not be used for unrelated studies

• A male participant must agree to use a contraception during the treatment period and for at least 180 days after the last dose of study treatment and refrain from donating sperm during this period

• A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:

‣ Not a woman of childbearing potential (WOCBP) OR

⁃ A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 180 days after the last dose of study treatment.

• Have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-2. Patients with ECOG PS 2 may be permitted only after discussion with the trial primary investigator (PI) (Dr. Grivas). Evaluation of ECOG PS is to be performed within 7 days prior to the date of enrollment.

• Absolute neutrophil count (ANC) \>= 1500/uL (within 10 days prior to the start of study treatment)

• Platelets \>= 100 000/uL (within 10 days prior to the start of study treatment)

• Hemoglobin \>= 9.0 g/dL or \>= 5.6 mmol/L (within 10 days prior to the start of study treatment)

• \* Criteria must be met without erythropoietin dependency and without packed red blood cell (pRBC) transfusion within last 2 weeks prior to study drug treatment

• Serum creatinine =\< 1.5 x upper limit of normal (ULN) OR measured or calculated creatinine clearance \>= 30 ml/min (glomular filtration rate \[GFR\] can be used in place of creatinine clearance; 24-hour urine collection can be used for more accurate estimate as needed) (within 10 days prior to the start of study treatment)

• \* Creatinine clearance (CrCl) should be calculated per institutional standard

• Total bilirubin =\< 1.5 x ULN OR direct bilirubin =\< ULN for participants with total bilirubin levels \> 1.5 x ULN (within 10 days prior to the start of study treatment)

• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\]) and Alanine aminotransferase (ALT) (serum glutamic-pyruvic transaminase \[SGPT\]) =\< 2.5 x ULN (within 10 days prior to the start of study treatment)

• International normalized ratio (INR) OR prothrombin time (PT) =\< 1.5 x ULN unless participant is receiving anticoagulant therapy (within 10 days prior to the start of study treatment)

• Activated partial thromboplastin time (aPTT) =\< 1.5 x ULN unless participant is receiving anticoagulant therapy (within 10 days prior to the start of study treatment)

• Patients must agree to undergo curative intent surgery.