Bladder Cancer – Causes, Symptoms, and Medications.

Introduction

Bladder cancer begins when healthy cells in the bladder lining, most commonly urothelial cells, change and grow out of control, forming a mass called a tumor. A tumor can be cancerous or benign. A cancerous tumor is malignant, meaning it can grow and spread to other parts of the body. A benign tumor means the tumor can grow but will not spread.

The bladder is a hollow organ in the pelvis with flexible, muscular walls. Its main function is to store urine before it leaves the body. Urine is made by the kidneys and is then carried to the bladder through tubes called ureters. When you urinate, the muscles in the bladder contract, and urine is forced out of the bladder through a tube called the urethra.

Structure of Urinary bladder

Start and spread of bladder cancer

The wall of the bladder has several layers, which are made up of different types of cells (see How is bladder cancer staged? for descriptions of the different layers).

Most of this cancers start in the innermost lining of the bladder, which is called the urothelium or transitional epithelium. As the cancer grows into or through the other layers in the bladder wall, it becomes more advanced and can be harder to treat.

Over time, the cancer might grow outside the bladder and into nearby structures. It might spread to nearby lymph nodes, or to other parts of the body. (If bladder cancer spreads, it often goes first to distant lymph nodes, the bones, the lungs, or the liver.)

Stages of bladder cancer

• Stage 0: The cancer cells are found only on the surface of the inner lining of the bladder. The doctor may call this carcinoma in situ.
• Stage I: The tumor has grown deeper into the inner lining of the bladder. But it hasn’t invaded the muscle layer of the bladder.
• Stage II: The tumor has invaded the muscle layer of the bladder.
• Stage III: The tumor has grown through the muscle layer to reach tissues near the bladder, such as the prostate, uterus, or vagina.
• Stage IV: The tumor has invaded the wall of the pelvis or abdomen, but cancer is not found in any lymph nodes. Or, the cancer cells have spread to at least one lymph node or to parts of the body far away from the bladder, such as the liver, lungs, or bones.

 

Types of bladder cancer

The type of bladder cancer depends on how it looks under the microscope. The 3 main types are:

1. Urothelial carcinoma. Urothelial carcinoma accounts for about 90% of all bladder cancers. It begins in the urothelial cells found in the lining the bladder. Urothelial carcinoma is the common term for this type of bladder cancer. Previously, it was called transitional cell carcinoma or TCC.
2. Squamous cell carcinoma. Squamous cells develop in the bladder lining in response to irritation and inflammation. Over time these cells may become cancerous. Squamous cell carcinoma accounts for about 4% of all bladder cancers.
3. This type accounts for about 2% and develops from glandular cells.

In addition to its cell type, it may be described as noninvasive, non-muscle-invasive, or muscle-invasive.

• Non-muscle-invasive. Non-muscle-invasive bladder cancer typically has only grown into the lamina propria. Non-muscle invasive cancer may also be called superficial cancer, although this term is being used less often because it may incorrectly suggest that this type of cancer is not serious.
• Muscle-invasive. Muscle-invasive bladder cancer has grown into the bladder’s wall muscle and sometimes into the fatty layers or surrounding tissue outside the bladder.

Background

Timeline	Developmental stages
19th century	The cytoscope develops. The first cystectomy for bladder cancer is performed.
1940s–1960s	Urine cytology emerges as a tool to detect recurrent bladder and urinary tract cancers
1970s	Cigarette smoking is linked to bladder cancer risk. First chemotherapy drug is released for bladder cancer.
1980s	Mitomycin chemotherapy is consolidated. Surgical advances improve bladder cancer survival. First successful combination chemotherapy for advanced bladder cancer is achieved.
1990s	Surgical techniques consolidate. New chemotherapies emerge to treat bladder cancer.
2000s	New chemotherapies prove to extend survival against bladder cancer. CT scan improves bladder cancer detection.
Recent years	As of 2010, it resulted in 170,000 deaths up from 114,000 in 1990 worldwide. Current treatment options for people with bladder cancer can include surgery, intravesical therapy, chemotherapy, radiation therapy and immunotherapy.

Prevalence at world wide

Globally, in 2010, bladder cancer resulted in 170,000 deaths up from 114,000 in 1990.[53] This is an increase of 19.4%, adjusted for increase in total world population.

In the United States, it is the fourth most common type of cancer in men and the ninth most common cancer in women. More than 50,000 men and 16,000 women are diagnosed with this cancer each year. Smoking can only partially explain this higher incidence in men. One other reason is that the androgen receptor, which is much more active in men than in women, plays a major part in the development of the cancer. It is the seventh most common cancer in the UK (around 10,400 people were diagnosed with the disease in 2011), and it is the seventh most common cause of cancer death (around 5,200 people died in 2012).

Causes and risk factors that leads to bladder cancer

• Bladder defects from birth
• Chemotherapy and radiation therapy
• Chronic bladder infections and irritations
• Exposure to certain chemicals including aromatic amines
• Low fluid consumption
• Personal or family history of bladder cancer
• Being male and/or white (women have lower rates of bladder cancer, as do African-Americans, Hispanics, Asian-Americans, and Native Americans
• Some medications and dietary supplements – pioglitazone (Actos) and aristolochic acid (mainly from plants in the Aristolochia family)
• Exposure to arsenic in drinking water

People who work in the following industries or who have the following professions also have an increased risk, likely due to exposure to certain chemicals:

• Manufacturing of rubber, leather, textiles and paint products
• Printing
• Painters
• Machinists
• Hairdressers
• Truck drivers.

Complications

• Emotional impact
• Continent urinary diversion
• Urostomy
• Erectile dysfunction
• Narrowing of the vagina

Symptoms and signs of Bladder cancer

Bladder cancer may cause these common symptoms:

• Finding blood in your urine (which may make the urine look rusty or darker red)
• Feeling an urgent need to empty your bladder
• Having to empty your bladder more often than you used to
• Feeling the need to empty your bladder without results
• Needing to strain (bear down) when you empty your bladder
• Feeling pain when you empty your bladder

These symptoms may be caused by bladder cancer or by other health problems, such as an infection.

Diagnosis and testing of bladder

• Urine tests: The lab checks your urine for blood, cancer cells, and other signs of disease.
• Cystoscopy: Your doctor uses a thin, lighted tube (a cystoscope) to look directly into your bladder. It may be done at your doctor’s office. This test can be uncomfortable because the doctor will insert the cystoscope into the bladder through your urethra. You may need local anesthesia for this test.
• Biopsy: Your doctor can remove samples of tissue with the cystoscope. A pathologist then examines the tissue under a microscope. The removal of tissue to look for cancer cells is called a biopsy. In most cases, a biopsy is the only sure way to tell whether cancer is present.

If bladder cancer is diagnosed, your doctor needs to learn the extent (stage) of the disease to help you choose the best treatment. Your doctor may order these tests:

• Blood tests: Blood tests can show how well the liver and kidneys are working.
• Chest x-ray: An x-ray of the chest can show a tumor in the lung.
• IVP: A dye that shows up on x-rays is injected into your blood vessel. The dye collects in your urine, which makes the bladder and the rest of the urinary tract show up on x-rays.
• CT scan: You may receive an injection of contrast material so your urinary tract and lymph nodes show up clearly in the pictures. The CT scan can show cancer in the bladder, lymph nodes, or elsewhere in the abdomen.
• MRI: You may receive an injection of contrast material. MRI can show cancer in the bladder, lymph nodes, or other tissues in the abdomen.
• Ultrasound: The picture of an ultrasound can show a tumor or blockage in the urinary tract.

Treatment and Medications

Several newer types of treatment are now being studied for use against bladder cancer.

Surgery

Some surgeons are using a newer approach to cystectomy in which they sit at a control panel in the operating room and maneuver robotic arms to do the surgery. This approach, known as a robotic cystectomy, lets the surgeon operate through several small incisions instead of one large one. This may help patients recover more quickly from surgery.

Intravesical therapy

Researchers are looking at a number of new medicines to see if putting them into the bladder after surgery can help lower the risk of the cancer coming back. The hope is to find some that are better and/or safer than currently used drugs such as Bacillus Calmette-Guérin (BCG) and mitomycin.

Photodynamic therapy

Photodynamic therapy (PDT) is now being studied to see if it’s useful in treating early stage bladder cancers. A light-sensitive drug is injected into the blood and allowed to collect in the cancer cells for a few days. Then a special type of laser light is focused on the inner lining of the bladder through a cystoscope. The light changes the drug in the cancer cells into a new chemical that can kill them.

An advantage of PDT is that it can kill cancer cells with very little harm to nearby normal cells. One drawback is that the chemical must be activated by light, so only cancers near the surface of the bladder lining can be treated in this way. The light can’t reach cancers that have grown deeper into the bladder wall or have spread to other organs.

 Immunotherapy

Immunotherapy is treatment that uses the body’s own immune system to fight the cancer.

Intravesical immunotherapy: One form of immunotherapy already used to treat some early bladder cancers is BCG, which is a type of intravesical therapy. When this germ is put into the bladder (in liquid form), it attracts immune cells to the bladder lining, which then attack cancer cells.

Immune checkpoint inhibitors: An important part of the immune system is its ability to keep itself from attacking the body’s normal cells. It does this by using “checkpoints” – molecules on immune cells that need to be turned on (or off) to start an immune response. Cancer cells sometimes use these checkpoints to avoid being attacked by the immune system.

Gene therapy

Adding or changing the actual genes inside cancer cells or other cells in the body – is another new treatment method being tested for bladder cancer. One approach to gene therapy uses special viruses that have been modified in the lab. The modified virus is put into the bladder and infects the bladder cancer cells. When this infection occurs, the virus injects a gene into the cells for GM-CSF, an immune system hormone that can help immune system cells to attack the cancer.

Preventing Bladder cancer

• Although there is not a guaranteed method to prevent, people can surely reduce the risk of getting it. For example, smokers are much more likely to develop bladder cancer than nonsmokers.
• Also, those exposed to industrial or environmental carcinogens such as azo dyes and arylamines are at a higher risk. People working with dyes, rubbers, textiles, paints, pesticides, insecticides, leathers, and chemicals are more vulnerable.
• Avoiding any potential carcinogens by inhalation, ingestion, or direct contact would certainly reduce risk not only of bladder cancer but also of other cancers.

Nutritional factors have been widely investigated in cancer prevention.

A few of those factors seem effective.

Ingestion of fruits and vegetables: A high intake of cruciferous vegetables, particularly green and yellow vegetables, has been shown to be linked with a reduced risk of bladder cancer, especially in nonsmokers

Fat consumption: A high intake of saturated fat was associated with a greater than two-fold increase in the incidence of bladder cancer.

Soy products: The isoflavone gentistein, a natural product, has been reported to have anti-urothelial cancer activity. Increased intake of soy products has been linked to reduced risk of breast, colon, and prostate cancer.

Vitamins: Vitamin A, also known as retinol, can be derived from carotenoids, which are rich in carrots. Vitamin B6 (pyridoxine) has also been reported to have a potential chemo preventive effect for bladder cancer. Vitamin C (ascorbic acid) has also been reported to reduce bladder cancer risk, but high concentration should be avoided because high concentration of Vitamin C was reported to have an adverse effect. Vitamin E was also reported to decrease bladder cancer mortality in patients who took vitamin E supplements, but overdose can be fatal.

Green tea: Epidemiological evidence pointed out that there is an inverse relationship between green tea consumption and bladder cancer risk