Pembrolizumab and BCG Solution in Treating Patients With Recurrent Non-Muscle-Invasive Bladder Cancer

Exclusion Criteria

• •Patients must have received one course of induction treatment with BCG (4-6 weekly doses), irrespective of the interval since last treatment; patients are allowed to have received any number of prior chemotherapy instillations
• •* NOTE: Patients may have received prior intravesical interferon
• •All patients must have imaging (computed tomography \[CT\] scan or magnetic resonance imaging \[MRI\]) documenting normal upper urinary tracts and absence of locally advanced bladder cancer within 60 days prior to study registration
• •Have a performance status of 0-2 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale
• •Absolute neutrophil count (ANC) \>= 1,500 /mcL within 14 days prior to registration
• •Platelets \>= 100,000 / mcL within 14 days prior to registration
• •Hemoglobin \>= 9 g/dL or \>= 5.6 mmol/L within 14 days prior to registration
• •Serum creatinine =\< 1.5 X upper limit of normal (ULN) OR measured or calculated (creatinine clearance should be calculated per institutional standard) creatinine clearance (glomerular filtration rate \[GFR\] can also be used in place of creatinine or creatinine clearance \[CrCl\]) \>= 60 mL/min for subject with creatinine levels \> 1.5 X institutional ULN within 14 days prior to registration
• •Serum total bilirubin =\< 1.5 X ULN OR direct bilirubin =\< ULN for subjects with total bilirubin levels \> 1.5 ULN within 14 days prior to registration
• •Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 X ULN within 14 days prior to registration
• •International normalized ratio (INR) or prothrombin time (PT) =\< 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants within 14 days prior to registration
• •Activated PTT (aPTT) =\< 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants within 14 days prior to registration
• •Females of child-bearing potential (FOCBP) and males must agree to use adequate contraception (e.g. hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 120 days following completion of therapy; should a female patient become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately;
• •* NOTE: A FOCBP is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria
• •* Has not undergone a hysterectomy or bilateral oophorectomy
• •* Has had menses at any time in the preceding 12 consecutive months (and therefore has not been naturally postmenopausal for \> 12 months)
• •FOCBP must have a negative urine or serum pregnancy test within 7 days prior to receiving the first dose of study medication; if the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
• •Patients must have the ability to understand and the willingness to sign a written informed consent prior to registration on study
• •* Note: subjects with =\< grade 2 neuropathy are an exception to this criterion and do qualify for the study
• •* Note: if subject received major surgery within 4 weeks prior to day -14, they must have recovered adequately from the toxicity and/or complications per PI discretion
• •Patients may not be receiving any other investigational agents within 4 weeks of the first dose of treatment
• •* NOTE: patients who have received acute, low-dose, systemic immunosuppressant medications (eg, one-time dose of dexamethasone for nausea) may be enrolled in the study; the use of inhaled corticosteroids and mineralocorticoids (eg, fludrocortisone) is allowed
• •* Ongoing or active infection requiring systemic treatment
• •* Symptomatic congestive heart failure (New York Heart Association cardiac disease class III or IV)
• •* Unstable angina pectoris
• •* Myocardial infarction within the previous 3 months
• •* Unstable cardiac arrhythmias
• •* Psychiatric illness/social situations that would limit compliance with study requirements
• •* Any other illness or condition that the treating investigator feels would interfere with study compliance or would compromise the patient's safety or study endpoints
• •* NOTE: patients with past hepatitis B virus (HBV) infection or resolved HBV infection (defined as the presence of hepatitis B core antibody \[HBc Ab\] and absence of HBsAg) are eligible; HBV deoxyribonucleic acid (DNA) must be obtained in these patients 14 days prior to study registration
• •* NOTE: patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV ribonucleic acid (RNA)
• •Patients with an active autoimmune disease requiring systemic treatment within the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs); replacement therapy (eg. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
• •Patients with a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents; subjects with vitiligo or resolved childhood asthma/atopy would be an exception to this rule; subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study; subjects with hypothyroidism stable on hormone replacement or Sjogren's syndrome will not be excluded from the study
• •* NOTE: history of radiation pneumonitis in the radiation field (fibrosis) is permitted
• •* Basal cell carcinoma of the skin
• •* Squamous cell carcinoma of the skin
• •* In situ cervical cancer