This prospective multi-center study of a new diagnostic test for microsatellite analysis (MSA) for bladder cancer will include clinical sites throughout the United States and Canada. Three groups will be included in this study. Two of the groups will include 200 (100 each group) participants without bladder cancer and will serve as control groups. These two control groups will be broken down into two cohorts. The first cohort, Control Group 1, will include 50 male and 50 female participants without a history of or current genitourinary (GU) diseases or devices with normal urinalysis and cytology determinations. The second cohort, Control Group 2, will include 100 participants with one of four disease processes requiring cystoscopy [benign prostatic hypertrophy (BPH), foreign body (urinary stones, stents, and catheters), infection, and hematuria], which have historically led to false positive urinary bladder cancer screening studies. The third group will include 300 participants with incident or recurrent superficial bladder tumors who are followed every 3 months with cytology and cystoscopic examinations for recurrence of their bladder tumors. MSA results will be compared with these standard examinations for recurrent disease. The results of MSA will be evaluated for both recurrent tumors as well as for anticipation of subsequent recurrent disease. The investigators will be blinded to the MSA assay results. No clinical decision regarding medical care or management will be based upon the MSA assay results alone. The contract laboratory responsible for performing the MSA assay will be blinded to all participant urinalysis, cytology, cystoscopic and pathology results to minimize bias. Goal 1: To determine sensitivity and specificity of microsatellite analysis (MSA) of urine sediment, using a panel of 15 microsatellite markers, in detecting bladder cancer in participants requiring cystoscopy. This technique will be compared to the diagnostic standard of cystoscopy, as well as to urine cytology. Goal 2: To determine the temporal performance characteristics of microsatellite analysis of urine sediment. Goal 3: To determine which of the 15 individual markers or combination of markers that make up the MSA test are most predictive of the presence of bladder cancer. Aim 1: This study will test the specificity of MSA in two groups of participants without bladder cancer─both healthy, normal controls as well as participants without bladder cancer who have conditions known to confound the performance of previous urinary tests for bladder cancer. Aim 2: This study will test the sensitivity of MSA in the presence of clinically evident, pathologically confirmed bladder cancer. Aim 3: This study will test the sensitivity and specificity of MSA for the detection of bladder cancer among participants undergoing surveillance for bladder cancer. Aim 4: This study will test the value of MSA to predict subsequent development of bladder cancer among participants with a history of bladder cancer.

Inclusion Criteria � Control Group 1 Participants must meet the following criteria to enroll in Group 1. � Healthy males and females without known history of or current urologic disease or devices � Age ≥40 � Never smokers (have never smoked cigarettes regularly i.e., at least one cigarette a day for a year or more) � No suspected exposure to environmental bladder carcinogens for greater than one year, particularly those listed in the occupational exposures under the exclusion criteria � Normal urinalysis � Normal urine cytology � Not presenting at the site for GU complaints (including urgency or frequency of urination) � No history of chemotherapy or radiotherapy for cancer. � Signed the informed consent document. � All lab results must be obtained on or after consent date and be entered into VSIMS within 6 weeks of consent date. Exclusion Criteria � Control Group 1 Participants must be excluded from Group 1 if they meet the following criterion. � History of radiotherapy or chemotherapy � History of GU cancer or other cancer with the initial diagnosis within the past 5 years (except non-melanoma dermatologic malignancy) � Exposure to known bladder carcinogens for greater than one year. Example occupations or exposures with established or suspect bladder cancer risks include, but are not limited to, the following:  aluminum industry;  aromatic amines;  coal gasification;  coal tars and pitches;  coke plant;  dye industry;  leather industry;  machinist;  painter;  rubber industry; and,  truck, bus or taxi drivers. Inclusion/Exclusion Criteria for Control Group 2 (n=100) Inclusion Criteria � Control Group 2 Participants must meet the following criteria to enroll in Control Group 2. � Presenting for GU complaints (requiring cystoscopy) � No evidence of current GU malignancy. Cancers other than GU are allowed as long as they are at least 5 years ago. Non-melanoma dermatologic are allowed regardless of time frame. � Age ≥40 � No history of chemotherapy or radiotherapy for cancer. � Signed the informed consent document � All lab results and procedures must be obtained on or after consent date and be entered into VSIMS within 6 weeks of consent date. (Except Culture and Sensitivity for Group 2d must be at least 2 weeks ago, and no more than 3 months ago, and document infection) Four subgroups (25 of each) will be included in Control Group 2. Participants may present with more than one of the below conditions. Group 2a: Current BPH: Definition: IPSS >12. Group 2b: Current Foreign bodies - stones, stents or catheters. Group 2c: Hematuria within past 6 weeks- either gross or microscopic. Group 2d: Current GU Infection - any kind, such as prostatitis, urinary tract infection (UTI), pyelonephritis, urethritis. Participants who are eligible due to urinary tract infection must have had the infection less than three months ago and have completed treatment for the infection. A prior culture and sensitivity report that documents the infection must be available. Cystoscopy cannot be performed until the patient�s physician confirms the patient does not have a urinary tract infection as per standard of care. The patient must not show any signs of a urinary tract infection or other GU infection (as determined by the urologist) at the time urine is collected for submission to the MSA laboratory. Exclusion Criteria � Control Group 2 Participants must be excluded from Control Group 2 if they meet the following criterion. � History of radiotherapy or chemotherapy � History of GU cancer or other cancer with the initial diagnosis within the past 5 years (except non-melanoma dermatologic malignancy) Inclusion/Exclusion Criteria for Cases Group 3 (n=300) Inclusion Criteria � Cases Group 3 Participants must meet the following criteria to enroll in Cases Group 3. � Endoscopic evidence confirmed by biopsy consistent with a superficial bladder urothelial malignancy � Age ≥ 40 � No history of GU cancer (except bladder cancer) Cancers other than GU are allowed as long as they are at least 5 years ago. Non-melanoma dermatologic are allowed regardless of time frame. � Agree to participate in the 2-year follow-up period, or standard of care follow-up for their condition � Signed the informed consent document � All lab results and procedures must be obtained on or after consent date and be entered into VSIMS within 6 weeks of consent date. Exclusion Criteria � Cases Group 3 Participants must be excluded from Cases Group 3 if they meet the following criterion. � Previous history of radiotherapy or systemic chemotherapy (other than intravesical therapy for bladder cancer) � Non-transitional cell carcinoma of the bladder, upper tract tumors, muscle-invasive tumors or superficial disease for which local therapy is not appropriate � History of GU cancer or other cancer with the initial diagnosis within the past 5 years (except non-melanoma dermatologic malignancy)

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Mark P. Schoenberg

Abigail Booker

The purpose of this research study is to evaluate a new method for detecting bladder cancer cells in urine. This new method is a laboratory test called microsatellite analysis. The test is experimental and therefore the accuracy of the results cannot be guaranteed.

Mark P. Schoenberg, M.D.

Allison Miller