Urinary Biomarkers in the Detection of Urothelial Carcinoma of the Bladder
Urinary Biomarkers in the Detection of Urothelial Carcinoma of the Bladder
To assess the persistence of bladder cancer-specific biomarkers in urine collected
 pre-operatively, in resected cancer tissue, and in urine collected post-operatively. A panel
 of sensitive and specific bladder cancer biomarkers will be used to establish a signature of
 disease in pre-operative patients with a positive diagnosis for bladder cancer by current
 standard of care (e.g., in-office cystoscopy, OR cystoscopy). The specificity of these
 markers will be assessed, as well as the degree of non-specific signal attributable to other
 sources of biomolecules, by analyzing resected tumor tissue for the same biomarkers. Finally,
 post-operative urine will be assessed for the presence of these markers. To the extent this
 biomarker panel can be determined to be specific and sensitive, it may serve as an indicator
 of the degree to which the surgical intervention successfully eradicated the underlying
 disease. The investigators also aim to assess the stability of a biomarker signature in urine
 but evaluating several patient specimens over various time points throughout the day.
Current standard of care in non-muscle invasive bladder cancer (NMIBC) relies on pathologic
 confirmation of negative margins as well as repeat transurethral resection. National
 Comprehensive Cancer Network (NCCN) and American Urological Association (AUA) guidelines
 specify a regular schedule of continued examination by cystoscopy and cytology to monitor the
 patient for the recurrence of disease.

 Physicians Choice Laboratory Services (PCLS) is validating a panel of biomarkers isolated
 from voided urine for their combined ability to reliably detect the presence of transformed
 cell populations. These markers include somatic mutations in a number of oncogenes that have
 been well established as important etiologic factors in the development of bladder cancer in
 the scientific and clinical literature. In addition, regional hypermethylation of the genome
 is evaluated, as is the presence or absence of specific proteins involved in the disease
 state. Through measurement of these biomarkers using next generation sequencing and
 immunoassays, PCLS has been able to establish both the analytical and clinical validity of
 these markers in diagnosing disease. The statistical correlation of these biomarkers with the
 presence of transitional cell carcinoma has resulted in the ability to define a distinct
 disease signature indicative of disease in preliminary studies. The current study aims to
 expand upon these findings in an effort to offer physicians an additional tool with which to
 manage bladder cancer.

 Hypothesis: Bladder cancer biomarkers will be elevated in preoperative and intraoperative
 urine specimens with direct correlation to the intact lesion(s), but will diminish
 significantly or disappear in urine specimens post-operatively with as a function of
 completion of resection. Further, the persistence of disease-specific biomarkers in urine
 post-operatively may correlate with the risk of recurrence or progression.

 Biomarker levels will be determined from pre-, intra- and post-operative urine specimens, as
 well as from resected bladder tissue and will be statistically compared for changes that
 correlate with presence or absence of visible disease. Biomarkers from tissue samples will be
 quantified and compared with urine sample values.

 The specific aims of the current proposal are to:

 SA1): Assess the stability of a biomarker signature in urine. To date, efforts across the
 biomarker field have relied on the detection of cancer in the context of a single patient
 specimen collected at a single point in time. The consistency of the biomarker signature
 across specimens provided by the same patient has not been fully described. The current study
 will assess the consistency with which the biomarkers composing the panel can be detected
 across urine specimens collected at multiple points in time in a subset of patients. This
 data will inform the utility of single point-in-time collection with regard to accurately
 defining the disease signature.

 SA2): Assess the persistence of bladder cancer-specific biomarkers in urine collected
 pre-operatively, in resected cancer tissue, and in urine collected post-operatively. A panel
 of sensitive and specific bladder cancer biomarkers will be used to establish a signature of
 disease in pre-operative patients with a positive diagnosis for bladder cancer by current
 standard of care (e.g., in-office cystoscopy). The specificity of these markers will be
 assessed, as well as the degree of non-specific signal attributable to other sources of
 biomolecules, by analyzing resected tumor tissue for the same biomarkers. Finally,
 post-operative urine will be assessed for the presence of these markers. To the extent this
 biomarker panel can be determined to be specific and sensitive, it may serve as an indicator
 of the degree to which the surgical intervention successfully eradicated the underlying
 disease.

 SA3): Determine whether persistence of biomarkers in patient urine post-operatively
 correlates with recurrence or progression. The same panel of markers detected in the
 pre-operative urine and tumor will be assayed in voided urine collected during routine
 follow-up surveillance visits for a period of one year. Biomarkers will be monitored for
 persistence and quantitative change in levels.
Inclusion Criteria:

 -  Suspected or confirmed urothelial type bladder cancer

 -  Scheduled for a transurethral resection of bladder tumor (TURBT) or cystectomy

 Exclusion Criteria:

 -  Less than 18 years of age

 -  Known concurrent upper urinary tract disease

 -  History of bladder or prostate radiation

 -  Patients who are unwilling or unable to give consent