According to the American Cancer Society, bladder cancer is responsible for about 5% of all new cancers in the United States.1Additionally, it is the sixth most common cancer in the United States.1Bladder cancer occurs when cells in the urinary bladder begin to grow uncontrollably. Fortunately, the rates of new bladder cancer cases have decreased. Men are about 3 to 4 times more likely to experience bladder cancer than are women.1About half of all bladder cancers are first diagnosed while the cancer is still confined to the inner layer of the bladder wall, which is known as noninvasive or in situ cancer. 

Risk Factors
The most common risk factor for bladder cancer in the United States is cigarette smoking.2In fact, about half of all bladder cancers are caused by cigarette smoking.2Evidence suggests that smoking cessation counseling may prevent bladder cancer.2Additional risk factors for developing bladder cancer include family historygenetic mutations; occupational exposures to chemicals in processed paint, dye, metal, and petroleum products; treatment with cyclophosphamide, ifosfamide, or pelvic radiation for other malignancies; Chinese herbs; arsenic exposure; Schistosoma haematobiumurinary tract infections; and neurogenic bladder and associated indwelling catheters.3          

Stage 0 Bladder Cancer Treatment
Stage 0 bladder cancer is noninvasive and does not involve lymph nodes or any distant metastasis.3This is an early stage of cancer that has not invaded the bladder wall beyond the inner layer. Treatment usually involves transurethral resection of bladder tumor (TURBT) with close follow-up and no further treatment or intravesical (administered directly into the bladder) chemotherapy to prevent recurrence. The TURBT procedure involves surgery, using an instrument placed up the urethra to remove abnormal tissues and tumors for analysis.  Immunotherapy with bacillus Calmette-Guérin (BCG) has been shown to be more effective than chemotherapy at preventing cancer recurrence.4However, BCG has more adverse effects than does chemotherapy. Treatment with BCG consists of an attenuated live strain of Mycobacterium bovis(related to the bacteria that causes tuberculosis) that is placed directly into the bladder through a catheter. Treatment is usually started a few weeks after TURBT and is given once a week for 6 weeks. Long-term maintenance therapy with BCG may be required. Common adverse effects may include bladder irritation, malaise, and fever.5Severe complications are rare and may include prostatitis, pneumonia, and nephritis.5

Stage I Bladder Cancer Treatment
Stage I bladder cancer has spread to the connective tissue layer of the bladder but has not reached the muscle layer.3Treatment usually involves TURBT as first-line therapy to determine the extent of the cancer. Generally, a second TURBT is necessary several weeks later. Once the cancer has been removed, intravesical BCG or mitomycin is usually given (Table 1). For cancer not removed by TURBT, treatment options include intravesical BCG or cystectomy, which is a partial or full bladder removal. Patients with contraindications to a cystectomy can receive radiation therapy, along with chemotherapy.3

Table 1. Stage 1 Bladder Cancer Treatment


Stage II Bladder Cancer Treatment
Stage II bladder cancer has spread to the bladder wall muscle layer.3Treatment initially involves TURBT to determine the extent of the cancer. Radical cystectomy, which involves removing the entire bladder and nearby lymph nodes, is usually necessary. Chemotherapy is usually given before or after surgery to prevent cancer recurrence. Evidence suggests that patients receiving chemotherapy prior to cystectomy may have better survival rates.8Neoadjuvant chemotherapy given prior to surgery can shrink the cancer, allowing for easier surgical removal.8The first-line chemotherapy regimen generally includes cisplatin, methotrexate, vinblastine, and doxorubicin (Table 2).9-12The cycle should be repeated every 28 days for a total of 3 cycles.9-12Atezolizumab (Tecentriq) can also be used as a first-line treatment for locally advanced or metastatic urothelial carcinoma in patients who are not eligible for cisplatin-containing chemotherapy.13

Table 2. Stage II Bladder Cancer Treatment


Stage III Bladder Cancer Treatment
Stage III cancer has reached the outside of the bladder and possibly has spread to nearby tissues or organs. Initial treatment generally involves TURBT to determine the extent of the cancer. Radical cystectomy is usually considered the standard treatment protocol. Neoadjuvant chemotherapy with cisplatin, methotrexate, vinblastine, and doxorubicin can be given prior to the cystectomy.

Stage IV Bladder Cancer Treatment
Stage IV cancer has reached the abdominal or pelvic wall or has spread to nearby lymph nodes or organs and is known as metastatic bladder cancer. Radical cystectomy may not remove all the cancer, so the treatment goal is to slow the growth and improve the quality of life. Chemotherapy, with or without radiation, is usually the first-line treatment for cancers that are nonmetastatic. Patients unable to tolerate chemotherapy may be treated with radiation therapy or an immunotherapy drug such as atezolizumab.

Prevention Strategies
Educate patients to quit smoking, as this can reduce the risk of developing bladder cancer.14Evidence also suggests that drinking plenty of water can reduce the risk of bladder cancer. Individuals should limit their exposure to certain chemicals in the workplace, such as aromatic amines and 4,4'-methylenebis(2-chloroaniline). These chemicals can be found in the products of the chemical, dye, and rubber industries, as well as hair dyes, paints, fungicides, plastics, cigarette smoke, metals, and motor vehicle exhaust.14  

End Note
Pharmacists can play an important role in smoking cessation counseling, as cigarette smoking is the most common risk factor for bladder cancer. Treatment depends on the bladder cancer stage and may involve TURBT, BCG, chemotherapy, radiation, or cystectomy. Encourage the use of neoadjuvant chemotherapy prior to cystectomy for stages II and III bladder cancer for better treatment outcomes. 
 
Jennifer Gershman, PharmD, CPh, is a medical writer and a Pharmacy Timescontributor residing in South Florida.

Reference
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