Chemotherapy and Bladder Cancer Death Risk

Chemotherapy is one of the most effective non-surgical modalities of care that is used to address advanced malignant lesions. In most cases, chemotherapy is preceded by the surgical removal of primary tumor before addressing the malignant foci throughout the body.

Cancer of urinary bladder is the 6^th most frequently reported malignant condition in the United States and is generally associated with a fairly high rate of morbidity and mortality if no treatment is sought. Different types of bladder cancer have different drugs therapies and therapeutic protocols. The most common histological varieties of bladder cancer are; transitional cell cancer, squamous cell carcinoma, adenocarcinoma and small cell carcinoma respectively.

There are various methods and modes of induction for the delivery of chemotherapeutic agent; most popular ones include systemic and local.

• Local Chemotherapy involves direct delivery of drug to the diseased tissue (or where neoplastic growth was first reported). For example, in case of bladder cancers, the drugs is introduced directly in the bladder region and thus therapy is also often referred to as intravesical therapy.
• In contrast, systemic chemotherapy involves the delivery of drugs in the form of oral pills or through injectable preparations via intravenous or intramuscular route. These drugs enters the bloodstream and travel throughout the patient’s body to attack disease cells throughout the biological system. It is imperative to mention that systemic regimen does affect the normal/ non-cancer cells of the body as a part of collateral damage. It can be given before the surgery in order to reduce the tumors size, to ensure easy removal from the body. Systemic chemotherapy is also associated with a lesser risk of tumor recurrence. Delivery of chemotherapy before the surgery is also known as neoadjuvant therapy.

In some cases, chemotherapy is combined with the radiation therapy to get a synergistic result and in order to treat the cancer more aggressively. Chemotherapy is the mainstay of the treatment for bladder cancer specially which are metastasized to distant parts of body.

According to a new study reported in the peer reviewed journal European Urology (1), investigators suggested that use of adjuvant chemotherapy after radical vasectomy in the management of undifferentiated bladder cancer or high risk muscle invasive bladder malignancy can decrease the overall mortality risk by 50%. Investigators also reported that bladder specific mortality is also reduced by 29%.

Chemotherapeutic agents frequently used to address Bladder Cancer

The chemotherapeutic agents that are used to address bladder cancer may vary; depending upon the nature of malignant lesion, size of tumor, mode of delivery, patient factors and results of genetic profiling.  In addition, the choice also varies, depending on the nature of therapeutic protocol. The following drugs are most commonly used to address bladder cancer with adjuvant radiotherapy protocol.

• Cisplatin
• Cisplatin along with 5-fluorouracil
• Mitomycin along with 5-fluorouracil

When chemotherapy is used alone as a mainstay therapeutic regimen in the setting of bladder cancer; these pharmacological agents are usually employed:

• Gemcitabine and cisplatin
• Methotrexate, vinblastine, doxorubicin, cisplatin (called MVAC)
• Carboplatin along with either paclitaxel or docetaxel (for patients whose kidney functions are minimized)

To minimize the untoward effects of multiple drugs used in chemotherapy, the patient should be ideally treated with single drug regimen in the beginning; such as only cisplatin, gemcitabine, 5-FU, paclitaxel or carboplatin. The process of chemotherapy includes two cycles, one is the treatment period and the other following it is the resting period so that the body takes time to recover from the loss.

Chemotherapy for the bladder cancer is problematic mostly for older patients (especially those who have a pre-existing medical condition). It is however imperative to mention that chemotherapy can still be used as a main-stay therapy since advanced cases of bladder malignancy are not suitable for surgical intervention. The decision to opt for chemotherapy depends mainly on patient factors (wishes, overall health etc.) and other elements like favorable circumstances of social, economic and health supports.

Common Side Effects of Bladder Chemotherapy

The side effect of chemotherapy depends largely on the type of drug used, the amount taken and period of treatment. Common side effects include:

• Nausea, vomiting and decreased appetite.
• Hair loss and discoloration.
• Mouth sores and ulcers.
• Diarrhea or constipation
• Increased susceptibility to infections.
• Fatigue and lethargy

The common side effects of therapy can be treated by adding other drugs in the therapeutic regimen (especially for nausea and vomiting to improve the quality of life and overall nutritional health). Some bladder cancer chemotherapeutic drugs can also lead to nerve fiber damage that may present as tingling, pain and numbness of the extremities. Some are reported to cause leukemia as well later in life. In most cases, chemotherapy for bladder cancer improves life expectancy by 44% by reducing the risk of recurrence as suggested by a new study reported in Journal of Cancer Research and Clinical Oncology (3). Therefore, chemotherapy should only be discontinued if the side effects outweigh the potential benefits.

References

1. Froehner, M., Koch, R., Heberling, U., Novotny, V., Oehlschlaeger, S., Hübler, M., … & Wirth, M. P. (2015). Decreased Overall and Bladder Cancer–Specific Mortality with Adjuvant Chemotherapy After Radical Cystectomy: Multivariable Competing Risk Analysis. European urology.

2. Eswara, J. R., Efstathiou, J. A., Heney, N. M., Paly, J., Kaufman, D. S., McDougal, W. S., … & Shipley, W. U. (2012). Complications and long-term results of salvage cystectomy after failed bladder sparing therapy for muscle invasive bladder cancer. The Journal of urology, 187(2), 463-468.

3. Kwon, T., Jeong, I. G., Lee, J., Lee, C., You, D., Hong, B., … & Kim, C. S. (2015). Adjuvant chemotherapy after radical cystectomy for bladder cancer: a comparative study using inverse-probability-of-treatment weighting. Journal of cancer research and clinical oncology, 141(1), 169-176.