Study Criteria

Inclusion Criteria:

  -  a.Urothelial carcinoma or mixed urothelial carcinoma arising from the bladder

  -  b.Age 18 or older

  -  Inclusions by cohort Cohort 1. Patients with localized muscle-invasive disease
     (cT1,cN0, M0) at the time of initial diagnosis or who have progressed from superficial
     disease (cT2) who have not had any systemic chemotherapy and who will be treated with
     upfront radical cystectomy. PriorTURBT and intravesical therapies are allowed but
     should not have been done within one week of CTC measurement. If the patient is found
     to have no evidence of tumor (pT0) upon evaluation of the cystectomy specimen, the
     patient will not be dropped. If the patient is found to have evidence of progression
     by any clinical evaluation performed within 2 months of the post-treatment sample, the
     patient will be dropped from Cohort 1 and included in Cohort 9 instead.

  -  Cohort 2. Patients with localized muscle-invasive disease (cT1, cN0, M0) at the time
     of initial diagnosis prior to definitivechemo-radiation. Prior TURBT and intravesical
     therapies are allowed but should not have been done within one week of CTC
     measurement. If the patient is found to have evidence of progression by anyclinical
     evaluation performed within 2 months of the post-treatment sample, the patient will be
     droppedfrom Cohort 2 and included in Cohort 9 instead.

  -  Cohort 3. Patients with localized muscle-invasive disease (cT1, cN0, M0) at the time
     of initial diagnosis or who have progressed from superficial disease (cT2) who have
     not had any systemic chemotherapy and who will be treated with neoadjuvant
     chemotherapy. Prior TURBT and intravesical therapies are allowed but should not have
     been done within one week of CTC measurement. If the patient is found to have evidence
     of progression by any clinical evaluation performed within 2 months of the
     post-treatment sample, the patient will be dropped from Cohort 3 and included in
     Cohort 9 instead.

  -  Cohort 4. Patients with metastatic disease (anyT, anyN, M1) at initial presentation or
     recurrent after definitive treatment prior to any salvage systemic chemotherapy. If
     the patient is found to have evidence of progression by any clinical evaluation
     performed within 2 months of the post-treatment sample, the patient will be dropped
     from Cohort 4 and included in Cohort 9 instead.

  -  Cohort 5. Patients with newly diagnosed non-muscle-invasive bladder cancer (T2) prior
     to any intravesical therapy. If the patient is found to have evidence of progression
     by any clinical evaluation performed within 2 months of the post-treatment sample, the
     patient will be dropped.

  -  Cohort 6. Patients with muscle-invasive bladder cancer after radical cystectomy with
     or without peri-operative systemic chemotherapy (pT2, anyN, M0) who will be treated
     with adjuvant radiation. If the patient is found to have evidence of progression by
     any clinical evaluation performed within 2 months of the post-treatment sample, the
     patient will be dropped from Cohort 6 and includedin Cohort 9 instead.

  -  Cohort 7. Patients with a history of muscle invasive bladder cancer (cT1, any N,M0)
     who have no evidence of disease at least 2 years after the date of radical cystectomy.
     If the patient is found to have evidence of progression by any clinical evaluation
     performed within 2 months of the post-treatment sample, the patient will be dropped
     from Cohort 7 but may be considered for inclusion in Cohort 4.

  -  Cohort 8. Patients with a history of muscle invasive bladder cancer (cT1, any N, M0)
     who have no evidence of disease at least 2 years after the completion of definitive
     chemo-radiation. If the patient is found to have evidence of progression by any
     clinical evaluation performed within 2 months of the post-treatment sample, the
     patient will be dropped from Cohort 8 but may be considered for inclusion in Cohort 4.

  -  Cohort 9. Patients who were initially included in Cohorts 1-6 but were found to have
     progression at the time of their post-treatment blood draw. Of note, patients may be
     included in more than one cohort over time so long as inclusion and exclusion criteria
     are met. In addition, twenty samples from normal controls without any history of
     malignancy will be used for this study but havealready been collected as part of a
     separate protocol.

Exclusion Criteria:

  -  pure squamous or pure adenocarcinoma bladder cancer histology. This exclusion may be
     waved at the discretion of the protocol PI. 2. Prior cancer diagnosed within 3 years
     of enrollment other than a prior bladder, prostate, or skin cancer. This exclusion may
     be waved at the discretion of the protocol PI.