Bladder Cancer

Overview

By Tina Shahian, PhD

Bladder cancer is a cancer that occurs in the bladder - the balloon-shaped organ that collects urine until it is excreted. It is caused by an uncontrolled growth of cells that form lumps called tumors. While some tumors are harmless, others continue to grow and eventually invade other organs. Bladder cancer is characterized by its location and growth through the four layers of the bladder wall. These include:

  • Urothelium or transitional epithelium: the stretchy innermost lining made up of urothelial or transitional cells.
  • Lamina propria: a layer of connective tissue, blood vessels and nerves.
  • Muscularis propria: a thick layer of muscles cells that push out urine during urination.
  • Fat: the outermost layer of fat cells that separate the bladder from neighboring organs.

picture of urinary bladder along with ureters and prostateThe most common type of bladder cancer is transitional cell (urothelial) carcinoma, which accounts for 90% of diagnosed cases. The affected cells resemble the urothelium cells of the inner bladder lining. Since urothelium cells also line other organs in the urinary tract, this type of cancer may also be found in the kidneys, ureters and urethra.

There are two subtypes of urothelial carcinomas, based on how the cells grow; papillary carcinomas form finger-like projections toward the inner hollow cavity of the bladder, while flat carcinomas do not form projections. Cancers are also classified as invasive or non-invasive based on the extent of growth through the bladder lining. Non-invasive tumors stay confined to the urothelium, while invasive tumors infiltrate the lamina propria and beyond - these cancers are more challenging to treat.

Other bladder cancers are squamous cell carcinoma, adenocarcinoma, small cell carcinoma and sarcoma. These cancers are much less common and each make up ~1% or less of all bladder cancers. Bladder cancer is often diagnosed early with good outcomes for patients. However, due to its high recurrence rate, continued monitoring is necessary.

Causes and Risk Factors

The cell cycle has built-in checks and balances that prevent uncontrolled cell division. When these checkpoints fail - as a result of mutations in the genetic code of key genes - cells grow into tumors. The molecular details of how cancer begins are not fully understood, but the known risk factors include:

  • Age. Bladder cancer is more common in older individuals - 9 out of 10 people affected are over the age 55.
  • Gender. Bladder cancer is 3–4 times more common in men. 
  • Race. Bladder cancer is more common in White individuals.
  • Family history and genetics. The risk of bladder cancer is higher for those with a family or personal history of bladder cancer, including other cancers of the urinary tract. Although genetics are rarely associated with bladder cancer, some inherited diseases pose an increased risk. For example, Lynch syndrome, which is a hereditary disease linked to colon cancer, also increases the chance of developing bladder cancer.
  • Chronic inflammation. Conditions that cause prolonged inflammation of the bladder (e.g. bladder/kidney stones and urinary tract infections) increase the risk of developing bladder cancer. The parasitic infection schistosomiasis, which is common in Africa and the Middle East, can also irritate the bladder and lead to cancer. 
  • Birth defects. Two types of birth defect increase a person’s likelihood for developing bladder cancer. The first occurs when the fetal connection between the bladder and the belly button fails to recede before birth. The second is when the inner lining of the bladder is exposed to the outside due to an abnormal opening in the abdominal wall.
  • Cancer treatment. Past treatment with the cancer drug cyclophosphamide (Cytoxan) or radiation therapy in the pelvis region can cause DNA damage in bladder cells and cause them to become cancerous.
  • Environmental toxins. Exposure to toxins and chemicals that are found in unregulated sources of drinking water or in certain manufacturing facilities have been linked to bladder cancer. These substances enter the bloodstream and eventually accumulate in the bladder, where they can affect cell integrity.
  • Poor hydration. Drinking ample fluids throughout the day helps flush out the bladder. Infrequent urination allows potentially harmful substances to sit in the bladder where they can damage cells.
  • Medication. Taking the diabetes drug pioglitazone (Actos) for more than one year is linked to bladder cancer.
  • Smoking. The harmful chemicals found in cigarettes enter the bloodstream, get filtered through the kidneys and accumulate in the bladder where they can irritate the lining and cause cancer.

Symptoms

The symptoms of bladder cancer include:

  • Blood in the urine
  • Frequent urination
  • Pain and difficulty while urinating.

Symptoms of advanced bladder cancer are:

  • Back or pelvic pain
  • Loss of appetite
  • Swollen feet.

Diagnosis and Treatment

The following tests are used to diagnose bladder cancer:

  • Physical exam. The doctor may perform a digital exam of the rectum or vagina to feel for tumors on the bladder.
  • Cystoscopy. This procedure allows doctors to visually inspect the bladder for tumors and remove samples for additional testing. It is carried out by inserting a thin tube (cystoscope) equipped with a lighted camera through the urethra and into the bladder. 
  • Biopsy. In order to confirm bladder cancer and determine the stage, a small tissue sample is removed (biopsy) for analysis. This is often performed during a cystoscopy. A needle biopsy is an alternate way of collecting cells by inserting a thin needle directly into the bladder. 
  • Urine analysis. A variety of urine tests are available to detect cancerous cells, protein markers for early-stage bladder cancer, or evidence of infection. 
  • Imaging. Various imaging tests are used to inspect the urinary tract and assess the level of cancer spread. An intravenous pyelogram (IVP) is an X-ray of the urinary tract that visualizes tumors with the aid of a contrast dye. Other imaging tests include computed tomography (CT), magnetic resonance imaging (MRI) and ultrasound.

Imaging tests are used to “stage” the cancer and determine the extent to which it has spread to other organs. Bladder cancer is staged from 1-4 (represented as Roman numerals I–IV).

  • Stage I: The cancer is present in the inner lining only.
  • Stage II: The cancer has spread to the muscle layer.
  • Stage III: The cancer has spread to the fatty layer and possibly neighboring organs.
  • Stage IV: The cancer has spread to neighboring organs and possibly to the lymph nodes, lungs, or other distant organs.

Treatment options vary depending on the stage of the bladder cancer and the health of the patient. In most cases, bladder cancer is caught early and is fully treatable. Treatment options for bladder cancer include:

  • Surgery. Early-stage bladder cancer tumors are removed surgically using transurethral resection (TUR) or segmental cystectomy. TUR is performed during a cystoscopy procedure and uses laser energy or an electric current to burn cancer cells. In segmental cystectomy, the affected portion of the bladder is removed without affecting normal bladder function. For advanced bladder cancer, radical cystectomy is performed to remove the entire bladder as well as neighboring organs. Following this procedure, additional surgery is performed to reroute the path of urine.
  • Chemotherapy. Chemotherapy is a systemic treatment that kills rapidly dividing cells (e.g. cancer cells) by interfering with DNA replication. It can be used to shrink tumors prior to surgery, or eliminate residual cancer cells following surgery. It is often the only viable treatment option for advanced bladder cancer.
  • Intravesical therapy. This treatment places therapeutics directly inside the bladder. Immunotherapies like the synthetic immune protein interferon alfa-2b or the bacterium Bacille Calmette-Guerin act by triggering a local immune response. Intravesical chemotherapy helps shrink tumors without a toxic effect on the remainder of the body.
  • Radiation. Radiation therapy is a targeted method of killing cells using high-energy radiation. It can be used for both early-stage and advanced bladder cancers, and is often used in combination with surgery and/or chemotherapy.

Prevention

Bladder cancer is caused by random molecular events that cannot be prevented. The best way to reduce the risk of developing bladder cancer is by eating a healthy diet, drinking plenty of fluids, avoiding hazardous chemicals and not smoking. Those with a family or personal history of urinary tract cancers can discuss screening options with their physician.

Sources

  • “Bladder Cancer”. American Cancer Society. Retrieved Jun 24, 2015. http://www.cancer.org/cancer/bladdercancer/index.
  • "Bladder Cancer". Mayo Clinic. Mayo Foundation for Medical Education and Research. Retrieved Jun 24, 2015. http://www.mayoclinic.org/diseases-conditions/bladder-cancer/basics/definition/con-20027606.
  • “Bladder Cancer” National Cancer Institute. NIH. Retrieved Jun 24, 2015. http://www.cancer.gov/types/bladder.