Bladder Cancer Treatment Protocols 

Updated: Feb 23, 2021
Author: Gary David Steinberg, MD, FACS; Chief Editor: E Jason Abel, MD 

Treatment Protocols

Treatment protocols for bladder cancer are provided below, including those for the following:

  • Chemotherapy
  • Immunotherapy
  • Systemic neoadjuvant and adjuvant therapy.

Non–muscle-invasive bladder cancer (Ta, Tis, T1)

Non–muscle-invasive bladder cancer (NMIBC) is divided into 3 groups: Ta, Tis, and T1:

  • Ta are noninvasive papillary lesions confined to the urothelium and have not penetrated the basement membrane.
  • Tis tumors are defined as severe cellular dysplasias usually in the absence of tumor formation.

  • T1 tumors are invasive cancers that have penetrated into underlying lamina propria but without any involvement of the muscularis propria.

Standard treatment for NMIBC is a complete transurethral resection of the bladder tumor (TURBT). Intravesical chemotherapy is generally used as prophylactic or adjuvant therapy after complete endoscopic resection; it is rarely used as therapy to eradicate residual disease that could not be completely resected

Postoperative adjuvant intravesical chemotherapy for non–muscle invasive bladder cancer[1, 2, 3]  

One postoperative intravesical dose (within 24 h, but usually immediately after resection) of the following has been shown to reduce recurrence, but not progression, of disease:

Non–muscle invasive bladder cancer (high grade)

High-grade or T1 disease:

  • For T1 tumors, TURBT alone is generally not adequate treatment; use of intravesical bacillus Calmette-Guerin (BCG) after TURBT is recommended[7]

Intravesical adjuvant immunotherapy for non–muscle-invasive bladder cancer[1, 8, 2] :

  • BCG 81 mg (TheraCys) or 50 mg (TICE BCG) in 50 mL sterile saline instilled into the bladder through a catheter and held for 2 h; instilled weekly for 6 wk[4]

  • Maintenance therapy: 81 mg intravesically given on days 1, 8, and 15 of months 3, 6, 12, 18, 24, and 36 after initiation

BCG-unresponsive non–muscle-invasive bladder cancer:

  • Pembrolizumab is indicated for treatment of BCG-unresponsive, high-risk NMIBC with carcinoma in situ (CIS) with or without papillary tumors in patients who are ineligible for, or have elected not to undergo, cystectomy. [9]  
  • Pembrolizumab 200 mg IV q3wk until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression
  • Valrubicin is indicated for intravesical therapy of BCG-refractory CIS of the urinary bladder in patients for whom immediate cystectomy would be associated with unacceptable morbidity or mortality. [10]
  • Valrubicin 800 mg added to 55 mL sterile saline instilled into the bladder through a catheter and held for 2 h; instilled weekly for 6 wk 

Muscle-invasive bladder cancer

T2-T4 without metastatic disease:

  • TURBT is the initial treatment recommendation to help identify the stage of the bladder cancer.

  • All muscle-invasive tumors are categorized as high-grade urothelial carcinomas.[11]

  • Radical cystectomy is the primary treatment for T2 and T3 tumors, with consideration for neoadjuvant chemotherapy.

  • Clinical evidence has demonstrated a overall survival benefit of neoadjuvant chemotherapy with methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC), compared with cystectomy alone.[12]

  • Current clinical data conflict on the role of adjuvant therapy in invasive bladder cancer, and additional trials are required; however, results from trials show delays of recurrence, so chemotherapy with MVAC or gemcitabine and cisplatin may be used (see chemotherapy for drug regimens, below)[1]

  • While no randomized studies have been performed comparing neoadjuvant with adjuvant therapy, many centers prefer to administer chemotherapy only after cystectomy and pathologic staging (ie, adjuvant chemotherapy)

First-line chemotherapy for muscle-invasive bladder cancer[1, 13, 14, 15, 12] :

  • Drugs currently used in the management of advanced bladder cancer include combinations of gemcitabine and cisplatin: Gemcitabine 1000 mg/m2 on days 1, 8, and 15 plus cisplatin 70 mg/m2 IV on day 1 or 2; repeat cycle every 28 d for a total of four cycles or

  • Other drug regimens include combinations of methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC): Methotrexate 30 mg/m2 IV on days 1, 15, and 22 plus vinblastine 3 mg/m2 IV on days 2, 15, and 22 plus doxorubicin 30 mg/m2 IV on Day 2 plus cisplatin 70 mg/m2 IV on day 2; repeat cycle every 28d for a total of 3 cycles

  • The FDA granted accelerated approval of atezolizumab, the first cancer immunotherapy that acts as a programmed cell death ligand inhibitor (PD-L1), as first-line treatment for locally advanced or metastatic urothelial carcinoma in patients who are not eligible for cisplatin-containing chemotherapy.[16]

  • Atezolizumab 1200 mg IV q3wk infused over 60 min until disease progression or unacceptable toxicity

  • Pembrolizumab 200 IV q3wk infused over 30 min until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression[17]

  • "Dose-dense" regimens for MVAC and GemCis, in which increased doses are administered along with doses of growth factor stimulants (eg, GM-CSF), have shown similar efficacy as conventional regimens.

Second-line chemotherapy for muscle invasive bladder cancer:

  • There are no definitive recommendations for second-line therapy.

  • Potential options for palliative therapy depends on the chemotherapy that was used for first-line treatment.

  • Chemotherapy options may include drugs such as cisplatin, gemcitabine, pemetrexed, carboplatin, vinblastine, and bleomycin, which have shown some beneficial effects in various trials.[1]

  • Atezolizumab 1200 mg IV q3wk infused over 60 min until disease progression or unacceptable toxicity[18]

  • Nivolumab 240 mg IV q2wk or 480 mg q4wk over 30 min until disease progression or  toxicity[19]

  • Avelumab 10 mg/kg IV q2wk infused over 60 min until disease progression or unacceptable toxicity [20]
  • Pembrolizumab 200 IV q3wk or 400 mg IV q6wk until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression[21, 22]

  • Erdafitinib 8 mg PO qd initially; increase to 9 mg PO qd based on serum phosphate levels and tolerability at 14-21 days; for metastatic urothelial carcinoma that has FGFR2 or FGFR3 genetic alterations and that progressed during or following at least 1 line of prior platinum-containing chemotherapy[23]  

  • Enfortumab vedotin 1.25 mg/kg IV on Days 1, 8, and 15 of a 28-day cycle; not to exceed 125 mg/dose for patients weighing 100 kg or greater; continue until disease progression or unacceptable toxicity[24]

 

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