Testing MK-3475 (Pembrolizumab) After Surgery for Localized Muscle-Invasive Bladder Cancer and Locally Advanced Urothelial Cancer

Inclusion Criteria:

   - PRE-REGISTRATION ELIGIBILITY CRITERIA

   - Histologically confirmed muscle-invasive urothelial carcinoma of the bladder, urethra,
   upper tract, or lymph node positive (LN+) disease; variant histology allowed as long
   as urothelial carcinoma is predominant (any amount of squamous differentiation is
   allowed); any component of neuroendocrine carcinoma is excluded

   - Paraffin tissue samples obtained by transurethral resection of muscle-invasive bladder
   tumor, upper tract resection, or radical
   cystectomy/nephrectomy/ureterectomy/nephroureterectomy/cystoprostatectomy or
   urethrectomy must be available; this specimen submission is mandatory prior to
   registration as results will be used for stratification; specimens from
   radical/definitive surgery (radical cystectomy/nephrectomy/ureterectomy
   /nephroureterectomy/cystoprostatectomy and LN dissection) are preferred over
   transurethral resection, if available

   - Patient must fit into one of the following three categories:

      - Patients who received neoadjuvant chemotherapy and pathologic stage at surgical
      resection is >= pT2 and/or N+ OR

      - Patients who are not cisplatin-eligible (according to >= 1 of the following
      criteria: Eastern Cooperative Oncology Group [ECOG] performance status of 2,
      creatinine clearance < 60 mL/min, grade >= 2 hearing loss, grade >= 2 neuropathy,
      or New York Heart Association class III heart failure and pathologic stage at
      surgical resection is >= pT3 or pN+) OR

      - Patients that decline adjuvant cisplatin-based or other systemic chemotherapy
      based on an informed discussion with the physician and pathologic stage at
      surgical resection is >= pT3 or pN+

   - The 7th edition of American Joint Committee on Cancer (AJCC) staging will be utilized;
   patient must have had radical cystectomy (cystoprostatectomy for men) and lymph node
   dissection (for bladder primary), or nephrectomy, nephroureterectomy or ureterectomy
   (for uppertract tumors) or urethrectomy (in addition to a radical cystectomy-either
   simultaneously or in the past) >= 4 weeks but =< 16 weeks prior to pre-registration;
   patients who have had a partial cystectomy as definitive therapy are not eligible

   - No gross cancer at the surgical margins; microscopic invasive urothelial carcinoma
   positive margins are allowed; carcinoma in situ (CIS) at margins is considered
   negative margins

   - No evidence of residual cancer or metastasis after surgery; patients with upper tract
   urothelial carcinoma must have a negative cystoscopy within 3 months prior to
   pre-registration; if the bladder has been removed a cystoscopy is not required

   - No metastatic disease (or radiologic findings "concerning" for metastatic disease) on
   cross-sectional imaging (according to Response Evaluation Criteria in Solid Tumors
   [RECIST] version [v]1.1 criteria)

   - No active autoimmune disease or history of autoimmune disease that might recur, which
   may affect vital organ function or require immune suppressive treatment including
   systemic corticosteroids; these include but are not limited to patients with a history
   of immune related neurologic disease, multiple sclerosis, autoimmune (demyelinating)
   neuropathy, Guillain-Barre syndrome, myasthenia gravis; systemic autoimmune disease
   such as systemic lupus erythematosus (SLE), connective tissue diseases, scleroderma,
   inflammatory bowel disease (IBD), Crohn's, ulcerative colitis, hepatitis; and patients
   with a history of toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome, or
   phospholipid syndrome because of the risk of recurrence or exacerbation of disease;
   human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral
   therapy with undetectable viral load within 6 months are eligible

   - No current pneumonitis or prior history of non-infectious pneumonitis that required
   steroids within the previous 5 years

   - Patients with vitiligo, endocrine deficiencies including type I diabetes mellitus,
   thyroiditis managed with replacement hormones including physiologic corticosteroids
   are eligible

   - Patients with rheumatoid arthritis and other arthropathies, Sjogren's syndrome and
   psoriasis controlled with topical medication and patients with positive serology, such
   as antinuclear antibodies (ANA), anti-thyroid antibodies should be evaluated for the
   presence of target organ involvement and potential need for systemic treatment but
   should otherwise be eligible

   - No known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or
   hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is
   detected)

   - No live vaccine within 30 days prior to the first dose of study drug; examples of live
   vaccines include, but are not limited to, the following: measles, mumps, rubella,
   varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guerin (BCG),
   and typhoid vaccine; seasonal influenza vaccines for injection are generally killed
   virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist)
   are live attenuated vaccines and are not allowed

   - No postoperative/adjuvant systemic therapy

   - No prior treatment with any therapy on the PD-1/PD-L1 axis

   - No treatment with any other type of investigational agent =< 4 weeks before
   pre-registration

   - No major surgery =< 4 weeks before pre-registration

   - No radiation therapy =< 4 weeks before pre-registration

   - No neoadjuvant chemotherapy =< 4 weeks before pre-registration

   - Not currently requiring hemodialysis

   - Age >= 18 years

   - Not pregnant and not nursing, because this study involves an investigational agent
   whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn
   are unknown

   - ECOG performance status =< 2

   - Absolute neutrophil count (ANC) >= 1,200/mm^3

   - Leukocytes >= 3,000/ mm^3

   - Platelet count >= 75,000/mm^3

   - Hemoglobin >= 9 g/dL or >= 5.6 mmol/L

   - Total bilirubin =< 1.5 x upper limit of normal (ULN)

      - Bilirubin for patients with Gilbert's =< 3.0 x ULN

   - Calculated (calc.) creatinine clearance >= 30 mL/min (using either Chronic Kidney
   Disease Epidemiology Collaboration [CKD-EPI] equation or Cockcroft-Gault formula)

   - Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 3.0 x upper limit
   of normal (ULN)

   - Serum albumin >= 2.8 g/dL

   - For women of childbearing potential only: a negative urine or serum pregnancy test
   done =< 7 days prior to pre-registration is required

   - REGISTRATION ELIGIBILITY CRITERIA: Results of central PD-L1 testing available; Q2
   Solutions will forward the PD-L1 results to the statistical center and the statistical
   center will notify the site that the result is available; since the results with be
   blinded to the site the notification from the Alliance registration/randomization
   office will serve as a confirmation of this eligibility criteria; after sites receive
   the confirmation e-mail from Alliance they can register the patient