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Bladder Cancer
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What Is Bladder Cancer?
The bladder is the hollow muscular organ in the lower abdomen that stores urine. Most bladder cancers develop in the inner lining of the bladder. Over time, the cancer might grow outside the bladder and into nearby structures. When bladder cancer spreads (metastasizes), it tends to go to distant lymph nodes, bones, the lungs, or the liver.
According to the American Cancer Society, more than 83,190 new cases of bladder cancer are diagnosed in the U.S. each year, resulting in about 16,840 deaths.
In Colorado there are approximately 1,200 new cases of bladder cancer each year.
Bladder cancer is more common in men than women. For men, it is the fourth most common type of cancer.
Bladder Cancer Prognosis and Survival Rates
Bladder cancer prognosis depends on the type of cancer and the stage at which it is diagnosed.
About two-thirds of all bladder cancers are discovered while the cancer is still only in the inner layer of the bladder wall. This is called non-invasive bladder cancer. The five-year survival rate for these patients is 90%.
One-third of cases are diagnosed while the cancer is still confined to the bladder but has spread into deeper layers of the bladder muscle. This is called localized bladder cancer. The five-year survival rate for these patients is 70%.
In rare cases, the cancer spreads beyond the bladder. The five-year survival rate for patients with regional bladder cancer, where the cancer has spread from the bladder to nearby structures or lymph nodes, is 36%.
Why Come to CU Cancer Center for Bladder Cancer
As the only National Cancer Institute Designated Comprehensive Cancer Center in Colorado and one of only four in the Rocky Mountain region, the CU Cancer Center has doctors who provide top-notch, patient-centered bladder cancer care and researchers focused on diagnostic and treatment innovations.
There are multiple bladder cancer clinical trials being offered by CU Cancer Center members at any given time. These trials offer patients alternatives to traditional bladder cancer treatment and can result in remission or increased life spans.
In addition, we offer a multidisciplinary care clinic for patients with bladder cancer. This includes reviews of tissue and pathology, imaging, and consultations with urologic oncologists, medical oncologists, and radiation oncologists.
Types of Bladder Cancer
Different types of bladder cells can become cancerous, and the type of cell affected determines the type of bladder cancer. They are categorized by looking at the cells under a microscope. Doctors use this information to understand the expected growth pattern and speed, as well as which treatments may work best.
Urothelial carcinoma is the most common form of bladder cancer, accounting for approximately 90% of all diagnoses. Urothelial cells line the inside of the bladder and are also found in the kidneys, the tubes (ureters) that connect the kidneys to the bladder, and the urethra. Because of this, urothelial carcinoma can also occur in those areas, but it is most common in the bladder. Urothelial carcinoma is sometimes called transitional cell carcinoma. Urothelial carcinoma can also have more aggressive cells like micropapillary, sarcomatoid, or plasmacytoid.
Squamous cell carcinoma accounts for 1% to 2% of all bladder cancer in the U.S., though it is more common in parts of the world where a certain parasitic infection called schistosomiasis is a common cause of bladder infections. Seen with a microscope, squamous cells are thin, flat cells. Squamous cell carcinoma may occur after extended irritation of the bladder, such as infection or long-term use of a urinary catheter. This type of bladder cancer is usually invasive.
Adenocarcinoma makes up about 1% of bladder cancer diagnoses. It begins in the cells of the mucus-secreting glands in the bladder. Most adenocarcinomas are invasive.
Small cell carcinoma accounts for less than 1% of bladder cancers. This cancer forms in nerve-like cells called neuroendocrine cells and usually grows quickly.
Sarcomas start in the muscle cells of the bladder and are very rare.
Bladder cancer tumors are also divided into two subtypes — papillary and flat — based on how they grow.
Papillary carcinomas grow in slender, finger-like projections from the inner surface of the bladder toward the hollow center, rather than into the deeper layers of the bladder wall. These are also called non-invasive papillary cancers.
Flat carcinomas do not grow toward the hollow part of the bladder. If a flat tumor is only in the inner layer of bladder cells, it is referred to as a non-invasive flat carcinoma or a flat carcinoma in situ.
If either a papillary or flat carcinoma grows into the deeper layers of the bladder, it is called an invasive urothelial carcinoma.
Risk Factors for Bladder Cancer
Bladder cancer has multiple risk factors. Risk factors are behaviors or conditions that increase a person’s likelihood of developing the cancer.
Smoking: Smokers are three to seven times more likely to develop bladder cancer than non-smokers. This may be because smoking causes toxic chemicals to accumulate in the urine, damaging the lining of the bladder. About half of all bladder cancers are attributed to smoking.
Exposure to certain chemicals: Workers in industries that use certain types of chemicals may have a higher risk of bladder cancer. These include people involved in the production or use of rubber, leather, textiles, dye, and paint products, as well as printing companies. Other workers with an increased risk include machinists, hairdressers (because of heavy exposure to hair dyes), and truck drivers (because of exposure to diesel fumes).
Exposure to arsenic: Arsenic is a naturally occurring chemical element. When found in drinking water, arsenic is associated with an increased risk of bladder cancer. The chances of being exposed to arsenic depend on where you live and whether you get your water from a well or from a public water system that meets acceptable standards for arsenic content. Drinking water is not a major source of arsenic in the United States.
Exposure to radiation: Patients who have been treated with radiation to the pelvis area are more likely to develop bladder cancer.
History of bladder cancer: People who have already had bladder cancer have a greater risk of developing it again, either in the same spot as before or in another part of the urinary tract.
Chronic bladder infections: Patients with chronic or repeated urinary infections or kidney and bladder stones seem to have a higher risk of bladder cancer, as do those who require long-term use of a urinary catheter.
The parasitic infection schistosomiasis (also known as bilharziasis) is also a risk factor for squamous cell carcinoma. Schistosomiasis is rare in the United States but more common in parts of Africa, South America, Southeast Asia, and the Middle East.
Genetics: People with a family history of bladder cancer have an increased risk of getting it themselves. Although this is sometimes related to environmental and lifestyle factors, family members may also share changes in some genes (like GST and NAT) that make it difficult for their bodies to break down certain toxins. This can make them more susceptible to bladder cancer.
Other gene syndromes that may increase the risk for bladder cancer include a mutation of the retinoblastoma (RB1) gene; Cowden syndrome, which is caused by mutations in the PTEN gene; and Lynch syndrome, also known as hereditary nonpolyposis colorectal cancer, or HNPCC.
Bladder birth defects: Although extremely rare, about one-third of adenocarcinomas are related to a birth defect where part of the prenatal connection between the belly button and the bladder (called the urachus) remains after birth.
Another rare birth defect called exstrophy — in which the bladder and the abdominal wall in front of the bladder don’t close completely in utero and are fused together — greatly increases a person’s risk of developing bladder cancer.
Age: Bladder cancer can occur at any age, but the risk increases with time. About 90% of people diagnosed with bladder cancer are over 55, and the average age of people when they are diagnosed is 73.
Gender: Bladder cancer is the fourth most common type of cancer in men, but it is less common in women. Both the number of new bladder cancer cases and the number of bladder cancer-related deaths have decreased in women in recent years. For men, incidence rates have decreased, but death rates have remained the same.
Race and ethnicity: Caucasians are about twice as likely to be diagnosed with bladder cancer than Black or Hispanic people, though Black patients are slightly more likely to be diagnosed when the cancer is at an advanced stage.
Symptoms of Bladder Cancer
Bladder cancer can usually be treated successfully if it is diagnosed early, before the cancer has spread. That’s why it’s important to understand the most common bladder cancer symptoms.
Most cases of bladder cancer are diagnosed when a patient notices blood in their urine, called hematuria. The urine may be orange, pink, bright red, dark red, or a brownish “tea or cola” color. In other cases, the amount of blood in the urine is too small to be seen and is discovered during a urine test (urinalysis) performed to assess other symptoms or as part of a general medical check-up.
Blood in the urine is not always an indicator of bladder cancer. It can signal an infection, kidney tumors, non-cancerous (benign) tumors, kidney or bladder stones, or other kidney diseases. Regardless, it is important to tell a doctor so a proper workup can be pursued.
Other symptoms of bladder cancer include:
- Frequent urination.
- Pain or burning during urination.
- Feeling the need to urinate, but not being able to.
- Back pain, especially in the lower back on one side of the body.
- Loss of appetite and weight loss.
- Fatigue.
- Swelling in the feet.
These symptoms can also be caused by other conditions, such as urinary tract infections (UTIs), bladder or kidney stones, an overactive bladder, or an enlarged prostate. They can also be signs of other forms of cancer besides bladder cancer.
Diagnosing Bladder Cancer
To diagnose bladder cancer, a doctor will start by asking about the patient’s medical and family history. Then, they will perform a physical exam. This may include a digital rectal exam and, for women, a pelvic exam. These exams allow the doctor to feel for a bladder tumor, determine its size, and potentially feel whether and how far it has spread.
Based on their findings, the doctor may refer the patient to a specialist, such as a urologist, for further diagnosis and treatment. Urologists are doctors who specialize in diseases of the urinary system and male reproductive system.
If the doctor or urologist suspects a patient may have bladder cancer, they will order more diagnostic tests. These may include all or some of the following.
Urine Tests for Bladder Cancer
If there is blood in the patient’s urine, the doctor may order a urine cytology test. For this test, a sample of urine is looked at under a microscope to see if there are any cancerous or pre-cancerous cells present. Cytology will also be performed on any bladder washings taken during a cystoscopy. Other available products can also be used to look for bladder cancer in the urine.
A urine culture may be done to rule out other symptom causes, such as a urinary tract infection. For this test, a sample of urine is put into a petri dish and analyzed for bacteria growth.
Some urine tests look for specific substances made by bladder cancer cells. These are called urine tumor marker tests.
Cystoscopy for Bladder Cancer
During a cystoscopy, a urologist uses a cystoscope — a long, thin, flexible tube with a light and a lens or a small camera on the end — to detect growths inside the bladder and assess the need for a biopsy or surgery. Most doctors feel that cystoscopy is the best method to diagnose bladder cancer.
For fluorescence cystoscopy (also known as blue-light cystoscopy), a light-activated drug is put into the bladder during routine cystoscopy. This drug is only absorbed by cancer cells. When the doctor shines a blue light through the cystoscope, cells containing the drug glow, indicating the presence of cancer. This is available at the University of Colorado. Narrow band imaging can also be used.
Biopsy for Bladder Cancer
If a cystoscopy indicated potential bladder cancer, the doctor will perform a biopsy. The most common type of biopsy for diagnosing bladder cancer is called a transurethral resection of bladder tumor (TURBT). During a TURBT, the doctor removes some or all of the tumor tissue and a sample of the bladder muscle near the tumor. These samples are analyzed by a pathologist to diagnose bladder cancer and find out the type of tumor and how deeply it has grown into the layers of the bladder.
Stages of Bladder Cancer
After diagnosing bladder cancer, the doctor will identify the stage of the disease. The stage is determined by several factors, including the size of the tumor and how far it has spread within or beyond the bladder. The stage impacts both the prognosis and treatment options.
Many of the same procedures used to diagnose bladder cancer are also used to identify the stage. Staging may also require additional tests, such as x-rays, computed tomography (CT or CAT) scans, magnetic resonance imaging (MRI), positron emission tomography (PET) scans, ultrasounds, and bone scans.
PET scans for bladder cancer are usually only recommended when there is an abnormality on a CT or MRI scan of possible bladder cancer spread.
Doctors usually use the TNM system to determine the stage of bladder cancer. The TNM system assesses the size and extent of the tumor (T-tumor) and whether it has ulcerated; whether the cancer has spread to nearby lymph nodes (N-node); and the presence and extent of metastasis (M-metastasis) to distant lymph nodes, bones, and organs
After the TNM assessment, the doctor will assign an overall stage number from 0 to 4, which can be further broken down based on the size of the original tumor and the extent to which the cancer has spread. In general, the lower the stage the better the prognosis and treatment options.
Bladder Cancer Stages
Stage 0a: The cancer is a non-invasive papillary carcinoma and is only on the surface of the inner lining of the bladder. It may have grown toward the hollow center of the bladder but has not grown into the muscle or connective tissue of the bladder wall. It has not spread to nearby lymph nodes or distant sites. The tumor is usually easy to remove.
Stage 0is: The cancer is a flat, non-invasive carcinoma and is only in the inner lining of the bladder. It has not grown toward the hollow part of the bladder, and it has not spread into the muscle or connective tissue of the bladder wall. It has not spread to nearby lymph nodes or distant sites. Despite the low stage number, this is a high-grade cancer and is considered aggressive since it can lead to muscle-invasive cancer. It is also known as flat carcinoma in situ.
Stage 1: The cancer has grown through the inner lining of the bladder and into the layer of connective tissue underneath (lamina propria). It has not spread to the muscle of the bladder wall or nearby lymph nodes or distant sites.
Stage 2: The cancer has spread into the muscle of the bladder wall. It has not reached the fatty tissue surrounding the bladder and has not spread to nearby lymph nodes or distant sites. This is also known as invasive cancer or muscle-invasive cancer.
Stage 3: The cancer has spread through the muscle of the bladder wall and into the fatty layer of tissue surrounding the bladder. It may have spread to the prostate (in men) or the uterus and vagina (in women). The cancer may have spread to nearby lymph nodes but has not metastasized to distant sites.
Stage 4: The cancer has spread into the pelvic wall or the abdominal wall or to distant lymph nodes or other parts of the body such as the bones, lungs, or liver.
Bladder Cancer Grades
In addition to the stages, doctors will often describe bladder cancer by grade and by whether they are invasive or non-invasive.
Bladder cancers are assigned grades based on how the cancer cells look under a microscope.
Low-grade bladder cancer looks more like normal bladder tissue. These are also called well-differentiated cancers. Patients with low-grade bladder cancer usually have a good prognosis.
High-grade bladder cancer looks less like normal bladder tissue. High-grade cancers are more likely to grow into the bladder wall and spread beyond the bladder. Often these need intravesical (chemotherapy or BCG) bladder treatments and/or further surgery.
Invasive and Non-Invasive Bladder Cancer
Bladder cancers are described as invasive or non-invasive based on how far they have grown into the wall of the bladder.
If the tumor stays in the inner layer of cells without growing into the deeper layers, it is referred to as non-muscle invasive.
If the tumor grows into the muscle layers of the bladder, it is referred to as invasive.
Treatments for Bladder Cancer
The treatment for bladder cancer is tailored to each patient and depends on the size of the tumors, the stage at which the patient is diagnosed, and the patient’s overall health and personal preferences. Bladder cancer care teams may include multiple health care specialists, such as primary care providers, urologists, medical oncologists, urologic oncologists, and radiation oncologists, as well as nurse practitioners, physician assistants, nurses, psychologists, social workers, and rehabilitation specialists.
Some of the primary treatments for bladder cancer include surgery, chemotherapy, radiation therapy, immunotherapy, and targeted drug treatments. Most patients receive at least one or more of these treatments or a combination. Some patients may also be eligible to participate in clinical trials — controlled research studies of new or experimental treatments or procedures that may fall into any of the treatment categories below.
Surgeries for Bladder Cancer
Surgery is one of the frontline treatments for bladder cancer and sometimes the only treatment required for early-stage cases. CU Cancer Center surgeons provide best-in-class surgical care for cancer patients.
Transurethral resection of bladder tumor (TURBT) is the most common procedure used to diagnose, stage and treat bladder cancer, especially early-stage and superficial (non-muscle invasive) tumors. During a TURBT, a cystoscope is inserted into the bladder through the urethra, then an instrument called a resectoscope is inserted through the cystoscope. The resectoscope has an electric wire loop that the surgeon uses to remove any tumors or abnormal tissues. Sometimes a surgeon will use a high-energy laser instead of or in addition to a resectoscope. Afterward, the surgeon may burn the tissue in the area where the tumor was removed, in a procedure known as fulguration.
As part of a TURBT procedure, patients may also receive an injection of chemotherapy drugs into the bladder to destroy any remaining cancer cells. The drugs are then drained from the bladder.
If the bladder cancer is invasive or is non-muscle invasive with certain high risk features, all of the bladder may need to be removed through a cystectomy. The surgeon will likely perform a radical cystectomy, removing the entire bladder and nearby lymph nodes (called lymph node dissection). Radical cystectomy sometimes also includes removal of the prostate and seminal vesicles (in men) and removal of the uterus, ovaries, fallopian tubes, cervix, and part of the vagina (in women).
The majority of cystectomies here at the CU Cancer Center are performed using robotic laparoscopic, or “keyhole” surgery, which uses multiple small incisions instead of one large one and robotic surgical instruments controlled by the surgeon.
This approach generally results in decreased surgical morbidity and shorter hospital stays.
Reconstructive Surgeries for Bladder Cancer
When the bladder is removed, the surgeon will have to create another way for the patient to store and pass urine. This is called urinary diversion. There are several types of reconstructive surgeries for patients who have undergone radical cystectomy. During an incontinent diversion, the surgeon creates a tube, called an ileal conduit, from a piece of intestine. This tube drains urine through an opening in the abdomen (called a stoma) and into a urostomy bag worn outside the body. Alternately, during a continent diversion, the surgeon uses a piece of intestine to create a small pouch, called a continent urinary reservoir, to hold urine inside the body. The patient will need to use a catheter to drain urine from the reservoir through a stoma in the abdomen a few times a day.
In a neobladder construction, the surgeon creates a new bladder out of a piece of intestine, which is then connected to the urethra. Although most patients with a neobladder can urinate normally, they will no longer have the urge to urinate and will need to learn to do so on a consistent schedule.
In an Indiana pouch or right colon pouch construction, the surgeon creates a reservoir out of a piece of intestine. A stoma comes through the abdominal wall. The patient then uses a catheter inserted through the stoma to drain urine on a scheduled basis.
Chemotherapy for Bladder Cancer
Chemotherapy uses drugs to destroy cancer cells. Chemotherapy can be administered throughout the body (systemic chemotherapy) or injected directly into the bladder (intravesical chemotherapy).
Systemic chemotherapy can be administered in pill form or injected into a vein or muscle. The drugs enter the bloodstream and attack cancer cells anywhere in the body. Systemic chemotherapy is often used before surgery to slow the growth of tumors or after surgery to destroy any remaining cancer cells. In certain situations, chemotherapy may also be combined with radiation therapy.
Chemotherapy is also usually the first line for bladder cancer that has spread outside the bladder.
The side effects of systemic chemotherapy can include fatigue, nausea and vomiting, hair loss, loss of appetite, mouth sores, constipation, diarrhea, and increased risk of infection, since the drugs affect the patient’s immune system.
Intravesical chemotherapy is usually administered by a urologist to treat superficial bladder cancer, where the cancer is only the lining of the bladder and has not penetrated the deeper muscle tissue of the bladder wall. It is commonly used after a TURBT procedure to kill any cancer cells that may remain in the bladder.
This form of chemotherapy can reduce the side effects normally linked to systemic chemotherapy, since the drugs are injected directly into the bladder rather than into the bloodstream. The main side effects of intravesical chemo include a burning feeling in the bladder and blood in the urine.
During intravesical chemotherapy, chemotherapy drugs are introduced into the bladder through a catheter and left inside for a set amount of time before being drained.
Immunotherapy for Bladder Cancer
Immunotherapy enhances the immune system’s ability to fight cancer. Like chemotherapy, it can be administered locally as intravesical immunotherapy or throughout the body.
The most common intravesical immunotherapy drug for treating early-stage bladder cancer is a weakened bacterium called Bacillus Calmette-Guerin (BCG). It was originally developed as a vaccine to protect against tuberculosis. BCG is injected into the bladder through a catheter, where it prompts the immune system to attack cancer cells. Because BCG triggers an immune system response, patients may experience flu-like symptoms such as fever, chills, achiness, and fatigue, as well as a burning sensation in the bladder and blood in the urine.
Systemic immunotherapy approaches to bladder cancer include immune checkpoint inhibitors or checkpoint blockade therapies that target the body’s checkpoint proteins, helping restore the immune system’s natural defenses against cancer cells. For bladder cancer, these include PD-1 and PD-L1 inhibitors. Another immunotherapy for bladder cancer is the use of monoclonal antibodies, man-made version of naturally occurring proteins made by the immune system to fight infection. These are designed to specifically attack cancer cells, reducing damage to healthy cells.
Targeted Drug Treatments for Bladder Cancer
Targeted therapies use drugs to inhibit the action of defective genes and molecules and halt the growth and spread of bladder cells while limiting harm to normal cells. One of the main targeted therapies for bladder cancer is erdafitinib (Balversa), which is used to treat patients with locally advanced or metastatic urothelial carcinoma who have Fibroblast growth factor receptor (FGRG) genetic mutations. Erdafitinib can cause eye problems, so patients taking this drug need to have regular eye exams and alert their doctor right away if they experience changes in vision.
Radiation Therapy for Bladder Cancer
Radiation therapy uses high-energy rays (such as x-rays) or particles (such as protons) to kill cancer cells. Although doctors rarely use radiation as a primary treatment for bladder cancer, it may be used before surgery to shrink the tumors or after surgery to reduce the risk of the cancer coming back or shrink tumors that could not be removed completely. Doctors may also use radiation as a palliative treatment for bladder cancer that is otherwise untreatable to relieve symptoms and decrease pain.
The University of Colorado (CU) Cancer Center partners with UCHealth, Children’s Hospital Colorado, and Rocky Mountain Regional VA to provide clinical care. Please make an appointment with one of our clinical partners to be seen by a CU Cancer Center doctor.
UCHealth Cancer Care - Anschutz Medical Campus
1665 Aurora Court Anschutz Cancer Pavilion
Aurora, CO 80045
720-848-0300
UCHealth Cherry Creek Medical Center
100 Cook Street
Denver, CO 80206
720-848-0000
UCHealth Cancer Center - Highlands Ranch
1500 Park Central Drive
Highlands Ranch, CO 80129
720-516-1100
UCHealth Lone Tree Medical Center
9548 Park Meadows Drive
Lone Tree, CO 80124
720-848-2200
Children's Hospital Colorado:
13123 East 16th Avenue
Aurora, CO 80045
720-777-6740
Rocky Mountain Regional VA Medical Center:
1700 North Wheeling Street
Aurora, CO 80045-7211
303-399-8020
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Information reviewed by Janet Kukreja, MD, in May 2022.