Bladder Cancer

Bladder cancer originates in the cells that line the urinary bladder.

The urinary bladder is the hollow, muscular, balloon-shaped organ that stores urine. Although the urinary bladder is the most common site for bladder cancer, it can also occur in other parts of the urinary system.

Bladder is one of the most common cancers, affecting almost 68,000 people in the United States and 9,000 people in Canada every year. In Canada, it is the fifth most common cancer.

More than 80,000 bladder cancer survivors are living in Canada right now. It remains one of the most expensive cancers to treat.

Pathophysiology

Like other cancers, the progression of bladder cancer involves uncontrolled growth of cells that line the urinary bladder. This may happen due to the accumulation of abnormal mutations that disturb the normal cellular checks that prevent cells from dividing uncontrollably.

Common risk factors of bladder cancer include:

• Smoking and tobacco use: Cigarette smoke and tobacco contain several carcinogenic agents that can activate abnormal growth signaling pathways, cause genomic damage, and trigger cancerous changes in the bladder epithelium.
• Chemical exposures: People working in occupations that involve heavy contact and exposure to hazardous chemicals are at a high risk of developing bladder cancer. Long-term exposure to chemicals that are involved in the manufacture of  dyes, rubber, leather, textiles, and paint products can increase the risk of cancer.
• Urinary infections: Repetitive use of urinary catheters, urinary tract infections, or conditions that cause inflammation to the bladder can cause changes to the epithelium lining the organ that over long periods can result in cancerous changes.
• Radiation exposure: Exposure to radiation can induce DNA damage and cause the cancer to develop.
• Gender: Males are more likely to develop bladder cancer in comparison to females.
• Age: Increasing age is correlated with the risk for developing bladder cancer
• Parasite infection: Infection from parasites can result in the exposure to parasitic chemicals and chronic infections that can trigger cancerous changes in the epithelium lining the bladder. This can occur through the activation of cancer-causing genes, DNA damage, and mutations that may occur due to products or toxins secreted by parasites. Therefore, people traveling to areas outside the U.S. where parasitic infections are a threat are at some risk of developing urothelial carcinoma induced by a parasitic agent.

Symptoms

Blood in the urine (hematuria) and painful urination are the most characteristic symptoms. The appearance of blood in the urine can cause the appearance of “cola-colored” or reddish urine. Sometimes these changes may be subtle and a proper urine the examination may be required to confirm these findings.

However, since these symptoms are commonly observed in other diseases, it is important to consult your doctor to determine the underlying cause of this symptom. Other associated symptoms of bladder cancer include Pelvic pain and frequent urination

Diagnosis

• Cystoscopy: The diagnosis of bladder cancer is frequently done through cystoscopy – a diagnostic method which involves inserting a small and narrow tube through the urethra.
• Biopsy: Based on your symptoms the clinicians may opt to collect a sample from the urinary epithelium.  This procedure is referred to as transurethral resection of bladder tumor (TURBT)
• Computerized tomography (CT), urogram, or retrograde pyelogram: involves the use of catheters to inject special dyes that can help the clinician view the morphology of the urinary tract in greater detail
• Cytology: A sample of the urine is analyzed for the presence of abnormal cancerous cells

Stages of Disease

There are many different types of cells that line our urinary bladder and urinary tract organs such as ureters, urethra and renal pelvis. These cells based on their morphology are called urothelial cells, transitional cells, squamous cells.

Based on where cancer originates bladder cancer can be classified as urothelial carcinoma, transitional cell carcinoma, squamous cell carcinoma or adenocarcinoma.

Urothelial carcinoma is more common accounting for greater than 90% of all bladder cancer cases. When the cancer is not localized and spreads to the distant organ it is called metastatic bladder cancer

Based on the aggressiveness of bladder cancer it can be classified as low-grade bladder tumor or a high-grade bladder tumor. When the cancer is localized to the lining of the bladder it is called superficial bladder cancer. When cancer spreads to muscle wall or nearby organs such as lymph node sit is called invasive bladder cancer.

Treatment

The treatment of bladder cancer depends on many factors. These include factor such as the age of the patients and aggressiveness of cancer determined by its stage, grade and metastatic nature (to what degree cancer has spread). Like other cancers, the treatment of bladder cancer can  be classified under four categories:

1. Surgery

Different surgical methods that are employed to physically remove the tumor or the affected tissue/organs that are affected by cancer.

• Transurethral resection (TUR) with fulguration: The surgeon inserts a small probe through the urethra and removes the cancerous tissue or tumor with a wire loop, laser or high energy electricity
• Radical cystectomy or partial cystectomy: Based on the aggressiveness of the tumor the surgeon may decide to remove a portion of the bladder (partial cystectomy) or the whole bladder (radical cystectomy)
• Urinary diversion: The removal of the bladder is accompanied by a Urinary diversion procedure to provide an alternative route for urine flow. In this method the surgeon

2. Chemotherapy

Chemotherapy involves using drugs that can stop the growth of cancer cells by killing them or blocking their division.

This can be done in two ways:

• Systemic chemotherapy: Chemotherapy can be administered directly into the bloodstream (systemic chemotherapy) by oral, intramuscular or intravenous routes.
• Intravesical therapy: This kind of localized therapy that delivers the drug directly to the cancer-affected organ. Intravesical chemotherapy therapy involves direct administration of the drug into the bladder by a catheter or other medical device that releases the drug.

Some chemotherapeutic drugs that have been approved for bladder cancer include: Cisplatin, Fluorouracil (5-FU), Mitomycin,  methotrexate, vinblastine, doxorubicin (Adriamycin),  gemcitabine.

These chemotherapeutic drugs that are used either alone or in combination for treatment of bladder cancer

3. Radiation Therapy

Radiation therapy can kill cancer cells and can be very effective in the treatment of bladder cancer. This type of therapy can be administered externally through the use of machine that sends radiation towards cancer or internally by use of needles, wires, or catheters that deliver radioactive substance near the vicinity of cancer. The dose and duration of radiation therapy is decided by the clinician based on the aggressiveness of the cancer

4. Immunotherapy

Immunotherapy has become very successful recently for many different types of cancer including bladder cancer. Immunotherapy involves arming your own immune system to attack cancer.

A class of drugs called checkpoint inhibitors activate the T cells of the immune system by breaking an inhibitory interaction. Some of these inhibitor interactions are thought to occur through the binding of PD-L1 on cancer cells and PD-1 on T cells. The patients are encouraged to inquire about many recent advances in Immunotherapy that have happened in the recent past.

Some drugs that are approved for the treatment of bladder cancer, that act through this mechanism are  Atezolizumab (Tecentriq^®), Avelumab (Bavencio^®), Durvalumab (Imfinzi^TM), Nivolumab (Opdivo), Pembrolizumab (Keytruda^®)

The use of Bacillus Calmette-Guérin (BCG) as a strategy to enhance immune reactivity against cancer has been very successful in bladder cancer. This strategy involves utilizing attenuated bacterial to activate the immune system and trick them into attacking cancer cells

Prevention

Some preventive strategies to avoid bladder cancer include avoiding harmful habits such as smoking and tobacco use that predispose you to bladder cancer. Minimizing exposure to toxic chemicals that pose a risk to bladder cancer is another avoidable strategy. Enrolling for routine and regular bladder cancer screening is another precaution of quickly diagnosing and treating the disease.

Written by Vinayak Khattar, Ph.D., M.B.A.

References:

1. Bladder cancer – Symptoms and causes. Mayo Clinic. https://www.mayoclinic.org/diseases-conditions/bladder–cancer/symptoms-causes/syc-20356104. Accessed May 16, 2019. 3. Bladder Cancer Facts. Bladder Cancer Canada. https://bladdercancercanada.org/en/bladder–cancer-facts/. Accessed May 16, 2019. 4. About Bladder Cancer. https://www.cancer.org/cancer/bladder–cancer/about.html. Accessed May 16, 2019. 5. What is bladder cancer? – Canadian Cancer Society. www.cancer.ca. http://www.cancer.ca/en/cancer-information/cancer–type/bladder/bladder–cancer/?region=on. Accessed May 16, 2019.