Bladder Cancer Treatment Protocols

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
 

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:

Mitomycin 40 mg in 20 mL sterile water

 
or

Epirubicin 80 mg in 40 mL sterile water


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

Intravesical adjuvant immunotherapy for non–muscle-invasive bladder cancer
:

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

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.

 

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.

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.

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.

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)

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
:

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.

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

“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.

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

Nivolumab 240 mg IV q2wk or 480 mg q4wk over 30 min until disease progression or  toxicity

Avelumab 10 mg/kg IV q2wk infused over 60 min until disease progression or unacceptable toxicity

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

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
 

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