Urothelial Carcinoma

Cancerous Cell Cycle

The cells with cancer undergo constant and rapid mitosis, and continue dividing despite the body’s signals to stop. Moreover, cancerous cells evade apoptosis (cell death), and therefore the excess of cells begin to pile on top of one another. This is what is known as a tumor. Another aspect of cells that is affected with cancer is differentiation. In a normal cell, they begin to specialize in structure and function once ready. Cancer cells, on the other hand, divide too quickly and don’t have enough time to differentiate.

Common Forms

Urothelial carcinoma is by far the most common type of bladder cancer at around 90-95% of bladder cancers. It, however, has some common variants that doctors and scientists classify it by. These include micropapillary, microcystic, nested, lymphoepithelioma-like, plasmacytoid, sarcomatoid, and giant-cell carcinoma. These are all found in the bladder, but can metastasize and spread to other parts of the body.

People at High Risk

• Men

• People 55+ years of age

• White individuals

• Smokers

• Workers in industries with toxic chemical exposure

  • paint, ink, rubber, etc.

• Those with a family history of urothelial carcinoma

Risk Factors/Known Causes (controllable)

Smoking

The use of tobacco can cause harmful chemicals to absorb into the bloodstream and accumulate in the patient’s urine. This can disrupt the urinary tract and lining of the bladder, increasing the risk of mutations and DNA damage. It is leading cause of urothelial carcinoma, as over 50% of bladder cancer patients are smokers.

Workplace Exposure

Chemicals used in the dye, paint, rubber, leather, textile, petroleum, and often printing industries have been linked to an increased risk in urothelial carcinoma, as they may alter the DNA of the cells that line the bladder.

Contaminated Water

Although not common in the United States, high levels of arsenic in drinking water can lead to urothelial carcinoma. Inorganic arsenic compounds can warp the body’s DNA repair mechanisms, increasing the risk of mutations in the cells lining the bladder.

Risk Factors/Known Causes (uncontrollable)

Age

The risk of developing urothelial carcinoma increases with age. 90% of bladder cancer patients are over 55, and the average age of diagnosis is 73.

Gender

Although the reason is still unclear, urothelial carcinoma is 3-4x more likely in men. However, tumors are often much more advanced and aggressive in women; therefore, the survival rates are significantly lower.

Race

Caucasian individuals tend to be approximately twice as likely to obtain bladder cancer in comparison to Black, Asian, Hispanic, and Native American individuals.

Family History

Gene mutations linked to urothelial carcinoma are most commonly developed later in life rather than inherited innately. Certain genetic conditions such as Cowden disease or Lynch syndrome, however, can increase risks of acquiring bladder cancer.

Diagnosis

The diagnosis of urothelial carcinoma is most commonly performed through a urine sample examination (urine cytology), a cystoscopy, a biopsy, or a computed tomography (CT) scan. In a cystoscopy, a thin, long instrument with a light and a lens is inserted through the urethra and into the bladder. This instrument is known as a cystoscope, and allows the doctor to examine abnormalities in the bladder. With urothelial carcinoma, a biopsy is usually conducted during a cystoscopy. It is a procedure in which a sample of tissue is removed to be viewed under a microscope for signs of cancer.

During computed tomography (CT) scan, the patient either ingests contrast dyes or has it inserted through their veins. Then, the CT machine takes pictures of the urinary tract to detect signs of cancer; the dyes are used to help something like a tumor show up more.

Symptoms

• Hematuria (blood in the patient's urine)

• Pain or burning during urination

• Frequent urination, especially at night

• Urge to urinate despite empty bladder

• Lower back pain on one side of the body

Treatment Options

Transurethral resection of bladder tumor (TURBT)

TURBT is often performed when the tumor is not yet muscle-invasive, and has been confined to the inner lining of the bladder. A wire loop is attached to a cystoscope, which is used to burn away the tumor with an electric current (fulguration) or simply cut the tumor out. Side effects typically last 1-4 weeks and may include pain and bleeding during urination as well as

frequent urination.

Radial Cystectomy

This operation entails the removal of the entire bladder, as well as nearby lymph nodes, organs, or glands that contain cancer. For men, this is often the prostate and seminal vesicles. For women, this can involve the urethra, ovaries, fallopian tubes, and/or part of the vagina. Side effects may include loss of surrounding organs, artificial bladder, bleeding, scarring from incision, and infection.

Partial Cystectomy

This is similar to a radial cystectomy, but done when the tumor is only in one area. The surgeon therefore only removes a portion of the bladder. Side effects may include reduced bladder capacity, bleeding, infection, and blood clots.

Immunotherapy

Immunotherapy boosts the body’s ability to recognize and fight against cancer cells. There are two types of immunotherapy–systemic and intravesical. Side effects may include fatigue, rashes, hematuria, fever, diarrhea, nausea, and joint pain.

• Systemic: Cancer cells have “checkpoints” that allow themselves to disguise as normal cells and hide from the immune system. Systemic immunotherapy involves immune checkpoint inhibitors, which block PD-1 and PD-L1. This way, the cancer cells can’t hide and the T-cells can recognize/kill them.

• Intravesical: Bacillus Calmette-Guerin (BCG) is a liquified bacteria inserted directly into the bladder through a catheter. It stimulates the immune system in the bladder to fight against the cancerous cells.

Radiation Therapy

Radiation therapy is the use of high-energy X-rays to alter the DNA of cancer cells, either killing them or preventing them from duplicating. Unlike systemic chemotherapy, radiation therapy only targets a specific part of the body rather than all of it. Side effects may include

skin reactions in the area hit by radiation, fatigue, vomiting/nausea, and frequent urination.

Chemotherapy

For urothelial carcinoma, chemotherapy is most commonly used to shrink a tumor before surgery or kill any remaining cancer cells after it. It is essentially the use of drugs and chemicals to kill or prevent the division of cancer cells. Side effects may include hair loss, nausea/vomiting, fatigue, being prone to infections, bruising/bleeding, loss of appetite, mouth sores, brittle nails, and dry/patchy/itchy skin.

Prognosis

The prognosis of urothelial carcinoma heavily depends on how much the cancer has spread. These are the 5-year relative survival rates of urothelial carcinoma, which measure how likely a patient is to survive after diagnosis in comparison to someone without cancer within 5 years.

• In-situ: 96%

• Localized: 74%

• Regional: 39%

• Metastatic: 9%

In situ: has remained where it originally formed (in the lining of the bladder)

Localized: only in the bladder

Regional: has spread to surrounding lymph nodes/structures

Metastatic: has spread to a distant tissues/organs such as the lungs or liver

Interesting Facts:

• 1 in 27 men in the United States will develop urothelial carcinoma at least once in their lifetime. Moreover, the recurrence rate for this type of cancer is 50-80%. It is extremely common for previous urothelial carcinoma patients to acquire it for a second time.

• Although slightly more outdated, urothelial carcinoma is also commonly known as transitional cell carcinoma (TCC).

• In 2022, there were an estimated 81,180 new cases of bladder cancer in the United States.