Consolidative Therapy After EV + Pembrolizumab in Muscle Invasive Bladder Cancer, REINFORCE Trial

Inclusion criteria

• Age \>= 18 at the time of screening
• Ability to understand and willingness to sign a written informed consent document
• Histopathologically confirmed cTxN1-3M0, cTxNxM1 or cT4bNxM0 muscle invasive bladder cancer at initial diagnosis
• Achieved a radiographic complete response (CR) or partial response (PR), per Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1 criteria and at the determination of treating physicians) after 3-9 cycles of induction EV + pembro
• If M1 after completion of EV + pembro, patients need to have =\< 5 sites of metastasis and all sites of metastasis should be extracranial
• Note: when counting the number of oligometastatic lesions, each lymph node lesion, whether pelvic or extrapelvic, is counted (for example, 2 distinct lymph nodes in the right external iliac basin count as 2 oligometastatic lesions; one extrapelvic and one pelvic node count as 2 oligometastatic lesions, etc). Five or fewer sites of metastasis applies after the completion of EV + pembro, not at initial diagnosis
• Be a candidate for consolidative radiation therapy (RT) to the pelvis (if indicated) or cystectomy (if indicated), and all sites of metastasis are amenable to RT
• Life expectancy \> 6 months
• Eastern Cooperative Oncology Group (ECOG) performance 0-2
• Absolute neutrophil count (ANC) \>= 1500 /mcL (within 180 days of trial registration)
• Platelets \>= 100,000/mcL (within 180 days of trial registration)
• Hemoglobin \> 9 g/dL (within 180 days of trial registration)
• Creatinine =\< 1.5 x upper limit of normal (ULN) OR \>= 60 mL/min (within 180 days of trial registration)
• Total bilirubin =\< 1.5 ULN OR direct bilirubin =\< ULN if total bilirubin \> 1.5 x ULN (within 180 days of trial registration)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 2.5 x ULN OR \< 5 x ULN if patient has live metastasis (within 180 days of trial registration)
• Albumin \>= 2.5 g/dL (within 180 days of trial registration)
• International normalized ratio (INR) or prothrombin time (PT) =\< 1.5 x ULN unless on anticoagulation therapy, in which case PT or partial thromboplastin time (PTT) should be in the therapeutic range (within 180 days of trial registration)
• PTT =\< 1.5 x ULN unless on anticoagulation therapy, in which case PT or PTT should be in the therapeutic range (within 180 days of trial registration)
• Participants of child-bearing potential must be willing to employ two highly effective and acceptable forms of contraception during, and for at least 90 days after the end of radiation therapy. Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within 72 hours of treatment initiation
• HIV-infected patients who are healthy and have a low risk of AIDS-related outcomes are included in this trial

Exclusion criteria

• Prior radiation therapy with field overlapping with current proposed radiation field, precluding delivery of meaningful dose of radiation
• Intracranial metastasis
• Any small cell component, or predominant (\> 50%) sarcomatoid or plasmacytoid histology
• Other active malignancy or clinically relevant malignancy within past 2 years, per discussion with the principal investigator
• Genetic conditions that increase sensitivity to radiation, such as Fanconi syndrome, ataxia telangiectasia, and Nijmegen breakage syndrome
• Active human immunodeficiency virus (HIV) not adequately controlled, active hepatitis B (e.g., hepatitis B virus surface antigen \[HBsAg\] reactive) or hepatitis C (e.g., hepatitis C virus \[HCV\] ribonucleic acid \[RNA\] \[qualitative\] is detected), as determined by standard of care testing
• Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
• Any other medical condition that may interfere with trial therapy delivery
• Adults with impaired decision-making capacity, as determined by the treating physician