Partial Cystectomy and Extended Pelvic Lymph Node Dissection with Standard of Care Systemic Therapy for the Treatment of Muscle-Invasive Bladder Cancer

PRIMARY OBJECTIVE:

I. To determine the 2-year distant recurrence-free survival (RFS) of partial cystectomy with extended pelvic lymph node dissection and SOC perioperative systemic therapy in selects patients with MIBC.

SECONDARY OBJECTIVES:

I. To determine the safety of partial cystectomy with extended pelvic lymph node dissection and SOC perioperative systemic therapy as measured using the Clavien-Dindo classification of post-operative complications.

II. To determine the 2-year RFS, muscle-invasive RFS, and cancer-specific survival of partial cystectomy with extended pelvic lymph node dissection and SOC perioperative systemic therapy in selects patients with MIBC.

III. To assess patient-reported health-related quality of life (HRQOL) outcomes with partial cystectomy with extended pelvic lymph node dissection in selects patients with MIBC as measured using the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)/Quality of Life Questionnaire-Muscle Invasive Bladder Cancer (QLQ-BLM30) instruments.

EXPLORATORY OBJECTIVE:

I. To evaluate for radiographic predictors on preoperative magnetic resonance imaging (MRI) of pathologic and oncologic outcomes following partial cystectomy with extended pelvic lymph node dissection in select patients with MIBC.

CORRELATIVE OBJECTIVES:

I. To assess for genomic predictors of treatment response with partial cystectomy with extended pelvic lymph node dissection in select patients with MIBC.

II. To assess circulating tumor deoxyribonucleic acid (ctDNA) and urinary biomarkers as predictors of RFS in select patients with MIBC treated with partial cystectomy with extended pelvic lymph node dissection and SOC perioperative systemic therapy.

OUTLINE:

Beginning within 60 days of transurethral resection of bladder tumor (TURBT), patients receive cisplatin intravenously (IV) over 2 hours on day 1 or over 1 hour on days 1 and 8 and gemcitabine IV over 30-60 minutes on days 1 and 8 of each cycle. Cycles repeat every 21 days for up to 4 cycles per standard of care in the absence of disease progression or unacceptable toxicity. Alternatively, patients may receive dose dense methotrexate on day 1, vinblastine IV on day 2, doxorubicin IV over 3-5 minutes on day 2, and cisplatin IV over 60 minutes on day 2 of each cycle. Cycles repeat every 14 days for 3-6 cycles per standard of care in the absence of disease progression or unacceptable toxicity. Within 30 days of completing chemotherapy or 60 days after TURBT (cisplatin ineligible patients), patients undergo partial cystectomy and may also undergo extended PLND at the discretion of treating urologic oncologist. Beginning after surgery, patients may also receive nivolumab IV over 30 minutes on day 1. Treatment repeats every 2 or 4 weeks per standard of care. Patients also undergo urine and blood sample collection, chest computed tomography (CT), CT or MRI, and CT urography or magnetic resonance (MR) urography, cystoscopy throughout the study. Additionally, patients may undergo TURBT throughout the study as indicated.

After completion of study treatment, patients are followed up at 90 days post-operative, every 3 months for years 1 and 2, and then every 6 months for up to year 5.