A Phase III Randomized Trial to Evaluate the Influence of BCG Strain Differences and T Cell Priming with Intradermal BCG Before Intravesical Therapy for BCG-Naïve High-Grade Non-Muscle Invasive Bladder Cancer

-Patients must have histologically proven Ta, CIS or T1 stage urothelial cell carcinoma of the bladder within 90 days prior to registration.
-Patients must have had all grossly visible papillary tumors removed within 30 days prior to registration or cystoscopy confirming no grossly visible papillary tumors within 30 days prior to registration.
-Patients with T1 disease must have cross-sectional imaging of abdomen/pelvis demonstrating no evidence of nodal involvement or metastatic disease (MRI or CT scan) within 90 days prior to registration.
-Patients with T1 disease must have re-resection confirming </= T1 disease within 90 days prior to registration.
-Patients must have high-grade bladder cancer as defined by 2004 WHO/ISUP.
-Patients must not have pure squamous cell carcinoma or adenocarcinoma.
-Patients' disease must not have micropapillary components.
-Patients must have no evidence of upper tract (renal pelvis or ureters) cancer confirmed by one of the following tests performed within 90 days prior to registration: CT urogram, intravenous pyelogram, MR urogram, or retrograde pyelograms.
- No other prior non-bladder malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated Stage I or II cancer from which the patient is currently in CR, or any other cancer from which the patient has been disease free for 5 years.
-Patients with localized prostate cancer who are being followed by an active surveillance program are also eligible.
- Zubrod performance status 0-2
-Patients must not have received prior intravesical BCG or intradermal BCG
-Patients must not be taking oral glucocorticoids at the time of registration.
-Patients must not be planning to receive concomitant biologic therapy, hormonal therapy, chemotherapy, surgery, or other cancer therapy while on study
-Patients must not have known history of tuberculosis.
-Patients must be negative for prior Tuberculosis infection as determined by a negative PPD test. If PPD is not available, then a negative Interferon Gamma Release Assay (IGRA) may be used. The PPD or IGRA test results must be obtained within 90 days prior to registration. PPD negativity is defined as < 10 mm diameter induration (palpable, raised hardened area) in the volar forearm at 48-72 hours following injection with standard tuberculin dose (5 units, 0.1 ml). For PPD readings done outside of 48-72 hour window, patients must have PPD test and reading repeated to confirm eligibility. See Section 18.1 for more information. IGRA positive is defined by the laboratory interpretation or using the package insert cut-off values. Any IGRA approved by the FDA is allowed, including the QuantiFERON®-TB Gold In-Tube test (QFT-GIT) or the T–SPOT® TB test (T-Spot).
-Patients must be >/= 18 years of age.
-Pre-study history and physical must be obtained within 90 days prior to registration. Patients must have a complete blood count (CBC) and basic metabolic panel including creatinine, potassium, chloride, BUN, CO2 and glucose within 28 days prior to registration.
-Patients must not be pregnant or nursing
-Patients must be offered the opportunity to participate in specimen banking for future studies, to include translational medicine studies, outlined in Section 15.0.
-Patients who can complete PRO forms in English or Spanish must complete the baseline Bladder Cancer Index, EORTC QLQ-C30 and AUASS forms.
-Patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines.
-As a part of the OPEN registration process (see Section 13.3 for OPEN access instructions) the treating institution's identity is provided to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system.

-Physician must confirm access to and availability of commercial BCG (Tice)