Pembrolizumab (MK-3475) and Bacillus Calmette-Guérin (BCG) as First-Line Treatment for High-Risk T1 Non-Muscle-Invasive Bladder Cancer (NMIBC) and High-Grade Non-Muscle-Invasive Upper Tract Urothelial Carcinoma (NMI-UTUC)]

Inclusion Criteria

• •Be willing and able to provide written informed consent/assent for the trial.
• •Histologically confirmed urothelial cancer by TURBT performed at MSK for patients in the T1 bladder cancer cohort or by high-grade cytology/biopsy by ureteroscopy performed at MSK for patients in the NMI-UTUC cohort.
• •TURBT within 8 weeks of protocol entry with complete resection of all papillary lesions for patients in the T1 bladder cancer cohort and ureteroscopy within 8 weeks of protocol entry with complete ablation of all papillary lesions with ureteroscopy or through antegrade percutaneous access for patients in the NMI-UTUC cohort..
• •Patients in the T1 bladder cancer cohort must have high risk, BCG-naïve non-muscle-invasive urothelial cancer defined as having one of the following disease states:
• •* T1 on restaging biopsy, plus CIS
• •* Multiple (≥ 1) T1 recurrences, plus CIS
• •* Multifocal T1 plus CIS
• •* T1b (extensive/deep invasion into lamina propria) plus CIS
• •* Lymphovascular invasion plus CIS
• •* T1 with variant histology: including micropapillary, nested variant, poorly differentiated, squamous, and glandular differentiation (the presence of variant histology will be based on MSKCC review), plus CIS.
• •* T1 with urothelial carcinoma of prostatic urethra (Ta, Tis, or T1 within prostatic urethra), plus CIS
• •* Large (≥3 cm) T1 tumor, plus CIS
• •Patients in the NMI-UTUC cohort must have high risk, BCG naïve NMI-UTUC, defined by having one of the following disease states:
• •* Histologic confirmed ureteroscopic biopsy with clinical stage Tis (also known as CIS), Ta, or T1 disease in the renal pelvis. Concomitant ureteral disease will be allowed if completely treated endoscopically.
• •* Clinical stage Tis confirmed by a positive high-grade selective cytology, coupled with ureteroscopic evaluation, confirming only flat eryethematous lesions and the absence of papillary tumors.
• •* Must not have received prior treatment with percutaneous BCG to the involved renal unit, but prior intravesical BCG for bladder cancer is acceptable.
• •Patients must have cross sectional imaging (CT or MRI urogram) within 3 months of protocol entry demonstrating no evidence of metastasis or radiographic evidence of muscle invasive disease.
• •Patient refusal of cystectomy and bilateral pelvic lymphadenectomy for the T1 bladder cancer cohort, or refusal of radical nephroureterectomy for NMI-UTUC cohort.
• •No prior intravesical BCG therapy for patients in the T1 bladder cancer cohort.
• •No prior radiation therapy for bladder cancer for patients in the T1 bladder cancer cohort. Prior radiation therapy for prostate cancer is allowed.
• •ECOG performance status of 0 or 1.
• •Age ≥ 18 years.
• •Female subjects of childbearing potential must be willing to use 2 methods of birth control, be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of the study medication (reference section 9.5.2). Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for \>1 year.
• •Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy.
• •Patients must not have other invasive malignancies within the past 5 years (with the exception of non-melanoma skin cancers, localized prostate cancer, and CIS of the cervix).
• •Required initial laboratory values:
• •* Absolute neutrophil count ≥ 1.5 x 10\^9/L
• •* Platelets ≥ 100 x 10\^9/L
• •* Hemoglobin ≥ 9 g/dL
• •* Bilirubin ≤ 1.5 times the upper limit of normal (x ULN)
• •* Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3.0 x ULN
• •* Calculated creatinine clearance ≥ 30 using the CKD-Epi formula