Patient must be >= 18 years of age.

Patient must not have any prior or current history of muscle-invasive (i.e., T2, T3, T4), locally advanced unresectable, or metastatic urothelial carcinoma as assessed on radiographic imaging obtained within 90 days prior to randomization. The radiographic imaging includes a computed tomography (CT) scan OR magnetic resonance imaging (MRI) of the abdomen/pelvis with intravenous contrast.
* Note: If a patient’s renal function does not permit the administration of intravenous contrast, either a CT scan or MRI of the abdomen/pelvis without intravenous contrast is acceptable.
** Note: Patients with a history of non-invasive (Ta, Tis) upper tract urothelial carcinoma that has been definitively treated with at least one post-treatment disease assessment (i.e., either cytology, biopsy, or imaging) that demonstrates no evidence of residual disease are eligible.

Patient must not have contraindications to any protocol agents (BCG, gemcitabine, or docetaxel) including the following:
* Immunosuppressed patients (defined as persons with congenital or acquired immune deficiencies whether due to concurrent diseases or immunosuppressive therapies) are not eligible. Patient must not be on immunosuppressive medication, including steroids (if doses exceed the equivalent of prednisone 10 mg daily). Short courses of steroids which are discontinued prior to randomization are acceptable. Patients on inhaled, intranasal and/or topical steroids are eligible.
* Patients with a history of severe hypersensitivity reactions to docetaxel, gemcitabine, and/or drugs formulated with polysorbate 80 are not eligible

Patient must have newly diagnosed, histologically confirmed high-grade non-muscle invasive urothelial carcinoma of the bladder (HGTa, HGT1, CIS, HGTa + CIS, or HGT1 + CIS stage) on transurethral resection of bladder tumor (TURBT) obtained within 90 days prior to randomization. The patient’s first diagnosis of bladder cancer must be made within 90 days of randomization

Patient must have all visible papillary tumor resected by the treating urologist at the site registering the patient to this protocol prior to randomization. If the treating urologist did not perform the TURBT, the treating urologist must perform a cystoscopy within 28 days prior to randomization to confirm the absence of visible papillary disease.

Patients must not have prostatic urethral involvement

Patient must have not received prior intravesical therapy for bladder cancer, with the exception of perioperative chemotherapy at the time of TURBT.

Patients with high grade T1 disease must have undergone a restaging TURBT within 90 days prior to Step 1 randomization.

Patient must not have pure squamous cell carcinoma or adenocarcinoma.

Patient must not have any component of neuroendocrine carcinoma (i.e., small cell or large cell).

Patient must not have any component of sarcomatoid, micropapillary, or plasmacytoid variant histology.

Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.

Patient must have Eastern Cooperative Oncology Group (ECOG) performance status 0-2.

Patient must not be pregnant or breast-feeding due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used.
* All patients of childbearing potential must have a blood test or urine study within 14 days prior to randomization to rule out pregnancy.
* A patient of childbearing potential is defined as anyone, regardless of whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months).

Patient must not expect to conceive or father children by using accepted and effective method(s) of contraception or by abstaining from sexual intercourse for the duration of their participation in the study. In addition, patients on Arm A must continue contraception measures for six months after the last dose of GEMDOCE for patients of child-bearing potential and continue for three month after the last dose of GEMDOC for male patients with partners of child-bearing potential. All patients must not breastfeed during their time on protocol treatment.

Patient may have received prior systemic gemcitabine or docetaxel use if it was for a non-bladder malignancy.

Patient must have the ability to understand and the willingness to sign a written informed consent document. Patients with impaired decision-making capacity (IDMC) who have a legally authorized representative (LAR) or caregiver and/or family member available will also be considered eligible.

Leukocytes >= 3,000/mcL (obtained =< 28 days prior to randomization).

Absolute neutrophil count (ANC) >= 1,500/mcL (obtained =< 28 days prior to randomization).

Platelets >= 70,000/mcL (obtained =< 28 days prior to randomization).

Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) (obtained =< 28 days prior to randomization).

Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamic-pyruvic transaminase [SGPT]) =< 3.0 x institutional ULN (obtained =< 28 days prior to randomization).

Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of randomization are eligible for this trial.

For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.

Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.

Patients will be enrolled in the QOL study if the patient can read and understand English, Spanish, or Chinese (simplified characters).
* NOTE: Sites cannot translate the associated QOL forms.

PRIMARY OBJECTIVE:
I. To determine the event free survival (EFS) of Bacillus Calmette-Guerin (BCG)- naïve high grade non-muscle invasive bladder cancer (NMIBC) patients treated with intravesical BCG versus (vs) gemcitabine hydrochloride (gemcitabine) and docetaxel (GEMDOCE).

SECONDARY OBJECTIVES:
I. To compare changes in cancer-specific and bladder cancer-specific quality of life (QOL) from baseline to treatment between BCG-naïve high grade NMIBC patients receiving BCG and GEMDOCE.
II. To determine the cystectomy free survival (CFS) of BCG-naïve high grade NMIBC patients treated with intravesical BCG vs GEMDOCE.
III. To determine the progression free survival (PFS) of BCG-naïve high grade NMIBC patients treated with intravesical BCG vs GEMDOCE.
IV. To determine the safety and toxicity of BCG-naïve high grade NMIBC patients treated with intravesical BCG vs GEMDOCE.

CORRELATIVE OBJECTIVES:
I. To test the hypothesis that somatic mutations in deoxyribonucleic acid (DNA) damage response genes and tumor mutational burden can predict whether an NMIBC patient will derive greater clinical benefit from BCG or GEMDOCE. 
II. To test the hypothesis that prognostic and immune-related gene signatures can predict whether a NMIBC patient will derive greater clinical benefit from BCG or GEMDOCE. 
III. To test the hypothesis that ribonucleic acid (RNA) molecular subtypes can predict whether a NMIBC patient will derive greater clinical benefit from BCG or GEMDOCE. 
IV. To determine the clinical utility of urinary tumor DNA analysis in detecting minimal residual disease and in predicting recurrence after BCG or GEMDOCE. 
V. To test the hypothesis that detectable plasma nucleic acid (circulating tumor DNA [ctDNA]) analysis is associated with worse progression-free survival in patients with NMIBC, with a focus on high-grade T1 bladder cancer. 
VI. To test the hypothesis that pathogenic/likely pathogenic germline variants in DNA damage response genes can predict whether a NMIBC patient will derive greater clinical benefit from BCG or GEMDOCE. 
VII. To test the hypothesis that immunoediting clonal selection, tumor immune microenvironment evolution, and molecular subtype switching are mechanisms of resistance to NMIBC therapy that could guide treatment selection and sequencing of therapies for recurrence events.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM A:
INDUCTION: Patients receive gemcitabine hydrochloride intravesically (IVES) and docetaxel IVES once a week (QW) for 6 consecutive weeks in the absence of disease progression or unacceptable toxicity. Patients then undergo a cystoscopy.

RE-INDUCTION: Patients with carcinoma in situ (CIS) or resected high-grade, non-muscle invasive (HgTa) receive gemcitabine hydrochloride IVES and docetaxel IVES QW for 6 weeks in the absence of disease progression or unacceptable toxicity. Patients then undergo a cystoscopy.

MAINTENANCE: Patients with complete response (CR) or resected low grade noninvasive bladder cancer (LgTa) after induction therapy receive gemcitabine hydrochloride IVES and docetaxel IVES monthly for up to 2 years in the absence of disease progression or unacceptable toxicity.

ARM B:
INDUCTION: Patients receive BCG IVES QW for 6 weeks in the absence of disease progression or unacceptable toxicity. Patients then undergo a cystoscopy.

RE-INDUCTION: Patients with CIS or resected HgTa receive BCG IVES QW for 6 weeks in the absence of disease progression or unacceptable toxicity. Patients then undergo a cystoscopy.

MAINTENANCE: Patients with a CR or LgTa after induction therapy receive BCG IVES QW for 3 consecutive weeks at months 3, 6, 12, 18, 24, 30 and 36 months after the start of Induction treatment (months 6, 9, 15, 21, 27, 33, and 39 for Re-Induction patients) in the absence of disease progression or unacceptable toxicity.

All patients also undergo blood and urine sample collection throughout the study, cystoscopy on study and during follow up, and computed tomography (CT) or magnetic resonance imaging (MRI) scan during screening. Patients may also undergo a biopsy on study.

After completion of study treatment, patients are followed up every 6 months for 5 years from the date of randomization.