Bladder Cancer Treatment Protocols 

Updated: May 11, 2017
  • Author: Gary David Steinberg, MD, FACS; Chief Editor: Neeraj Agarwal, MD  more...
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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 [1]

  • Non-muscle invasive bladder cancers are 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 non-muscle invasive bladder cancer 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) has been shown to reduce recurrence, but not progression, of disease
  • Mitomycin 40 mg in 20 mL sterile water [4] or
  • Epirubicin 80 mg in 40 mL sterile water [5] or
  • Thiotepa 30 mg in 15 mL sterile water or
  • Doxorubicin 50 mg in 20 mL sterile water

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 [6]

Intravesical adjuvant immunotherapy for non–muscle invasive bladder cancer [1, 7, 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

Muscle-invasive bladder cancer

T2-T4 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 [8]
  • Radical cystectomy is the primary treatment for T2 and T3 tumors, with consideration for neoadjuvant chemotherapy
  • Clinical evidence has demonstrated a benefit to neoadjuvant chemotherapy with methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC), compared with cystectomy alone
  • 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)

First-line chemotherapy for muscle-invasive bladder cancer [1, 9, 10, 11, 12] :

  • Drugs currently used in the management of advanced bladder cancer include combinations of gemcitabine and cisplatin: Gemcitabine 1000 mg/m 2 on days 1, 8, and 15 plus  cisplatin 70 mg/m 2 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/m 2 IV on days 1, 15, and 22 plus  vinblastine 3 mg/m 2 IV on days 2, 15, and 22 plus  doxorubicin 30 mg/m 2 IV on Day 2 plus  cisplatin 70 mg/m 2 IV on day 2; repeat cycle every 28d for a total of 3 cycles
  • In April 2016, the FDA granted accelerated approval of atezolizumab as first-line treatment for locally advanced or metastatic urothelial carcinoma in patients who are not eligible for cisplatin-containing chemotherapy [15]
  • Atezolizumab 1200 mg IV q3wk infused over 60 min until disease progression or unacceptable toxicity
  • "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]
  • In May 2016, the FDA granted accelerated approval of atezolizumab, the first cancer immunotherapy that acts as a programmed cell death ligand inhibitor (PD-L1) for the treatment of urothelial carcinoma
  • Atezolizumab 1200 mg IV q3wk infused over 60 min until disease progression or unacceptable toxicity [13]
  • In February 2017 and April 2017, 3 other PD-L1 inhibitors, nivolumab, durvalumab and avelumab, were also granted accelerated approval for urothelial carcinoma
  • Nivolumab 240 mg IV q2wk infused over 60 min until disease progression or unacceptable toxicity [14]
  • Durvalumab 10 mg/kg IV q2wk infused over 60 min until disease progression or unacceptable toxicity [16]
  • Avelumab 10 mg/kg infused over 60 min until disease progression or unacceptable toxicity [17]