Bladder cancer makes up about 4% of the cancers diagnosed in the United States[1], and is the fourth-most common type of cancer in men (though it is less common in women). The main role of the bladder is to store and eliminate urine. The bladder is a hollow organ whose wall is made up of several layers; most often bladder cancer begins in the innermost lining of the bladder, known as the urothelium or transitional epithelium.
The most common early symptoms of bladder cancer include blood in the urine, frequent or painful urination, an urge to urinate when the bladder isn’t full, and unexplained back pain[2]. Cancer which has progressed may also cause an inability to urinate, pain in the abdomen or bones, unintended weight loss or loss of appetite, swelling of the feet, and fatigue.
Bladder cancer can present with various subtypes[3] that begin in different types of cells, each characterized by distinct features and biological behaviors:
Urothelial carcinoma: This is by far the most common form of bladder cancer, accounting for over 90% of diagnosed bladder cancers. Urothelial cells line the bladder, as well as the urethra, ureters (which connect the bladder and the kidneys), and small portions of the kidneys.
Squamous cell carcinoma: About 3-5% of bladder cancers are squamous cell carcinomas (SCCs), forming in the squamous cells of the bladder.
Adenocarcinoma: These cancers begin in gland-forming cells, but account for just 1-2% of bladder cancers.
Sarcoma: Sarcomas begin in the body’s connective tissues. While these can originate in the bladder, they’re exceedingly rare.
The National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) database tracks bladder cancer based on how far the cancer has spread:
Non-invasive/In situ: The cancer is still exclusively in the innermost lining of the bladder, and has not spread to deeper layers of the organ.
Localized: There is no sign that the cancer has spread outside of the bladder.
Regional: The cancer has spread outside the bladder to nearby structures or lymph nodes.
Distant: The cancer has spread to distant parts of the body such as the lungs, liver or bones
The 5-year survival rate at each stage is shown below:
Incidence
Below is the overall incidence of bladder cancer by age group:
As previously noted, men are far more likely to develop bladder cancer than women.
Risk Factors
There are several confirmed risk factors that contribute to an individual’s risk for bladder cancer:
Gender at birth: Bladder cancer is significantly more prevalent amongst men than women. For people assigned male at birth, the overall lifetime risk of developing bladder cancer is about 1 in 28, whereas for people assigned female at birth, that risk decreases significantly to 1 in 89.
Smoking & secondhand smoke exposure: Smoking and secondhand smoke increases the risk of bladder cancer threefold, and is thought to cause about 50% of all bladder cancers.[4] Tobacco smoke contains numerous carcinogens that can lead to genetic mutations and uncontrolled cell growth, ultimately resulting in cancer. Quitting smoking at any age can significantly reduce the risk of cancer and other smoking-related diseases. The body begins to repair itself almost immediately after quitting, with the risk of cancer decreasing over time. Even individuals who have smoked for many years can benefit from quitting, as the risk decreases with each year of abstinence.
Chemotherapy and radiation exposure: Radiation impacts cancer risk by damaging DNA in cells, which can lead to mutations and ultimately the development of cancer. Certain occupations, living at higher altitudes, and common medical procedures–particularly radiation treatments of the pelvis area–can all increase your risk of bladder cancer. Long-term use of the chemotherapy drug cyclophosphamide can also irritate the bladder, raising your risk.
Red meat consumption: Red meat consumption has been associated with several cancers, including bladder. Red meat contains compounds such as heme iron and saturated fats, which have been hypothesized to contribute to cancer risk through mechanisms like oxidative stress and inflammation. The risk may be amplified depending on how red meat is cooked. When cooked at high temperatures or over an open flame (such as through grilling), carcinogenic compounds known as heterocylic amines (HCAs) and polycyclic aromatic hydrocarbons (PAHs) are formed.
Workplace chemical exposure: Exposure to chemicals common in certain industries has been shown to increase the incidence of bladder cancer. Firefighters, hairdressers, truck drivers, workers at printing companies, and makers of rubber, leather, textiles, and paint products are at risk of this type of exposure.
Health conditions:
Type 2 diabetes: Research has consistently shown that individuals with diabetes have an increased risk for certain types of cancer, including bladder. This risk is particularly heightened in individuals with type 2 diabetes. Insulin resistance is believed to contribute to this link, along with chronic inflammation which is common amongst diabetics.
Chronic cystitis: Chronic urinary tract inflammation and/or infection, including inflammation from prolonged use of a catheter, increases the risk for developing bladder cancer.
Schistosomiasis infection: This parasitic infection that’s exceedingly rare in the US (but more common in other parts of the world) has been shown to increase your risk.
HPV infection: Several studies indicate HPV infection can both increase risk for bladder cancer and lead to worse outcomes after diagnosis.
Bladder birth defects: Bladder birth defects such as exstrophy increase the risk for bladder cancer later in life.
Genetic conditions: Cowden disease (caused by a mutation to the PTEN gene), Lynch syndrome, and mutations to the retinoblastoma (RB1) gene all increase the risk of bladder cancer.
Exposure to chlorine or arsenic in water[5]: Studies have shown that exposure to chlorinated water–either in drinking water or via prolonged time in swimming pools–increases the risk of bladder cancer. Drinking water that contains arsenic–most likely when drinking well water, as the substance occurs naturally in the soil–carries similar risks.
Age: About 9 out of 10 people who develop bladder cancer are over the age of 55 (the average age at time of diagnosis is 73).
Protective Factors
Several factors have been shown to have protective effects against bladder cancer:
Maintaining a healthy weight: Numerous studies have linked higher BMI to increased risk of various types of cancer, including bladder cancer in both men and women. Excess body fat can lead to higher levels of estrogen and insulin, as well as increased production of insulin-like growth factors. Higher BMI is also associated with chronic low-level inflammation, which can cause DNA damage over time and contribute to the development of cancer. Maintaining a healthy weight helps you to avoid these risks.
Daily use of NSAIDs: Nonsteroidal anti-inflammatory drugs (NSAIDs) are a class of medications commonly used to relieve pain, reduce inflammation, and lower fever, and they have also been shown to reduce cancer risk with regular use, including the risk of bladder cancer. In addition to their anti-inflammatory properties, NSAIDs have been shown to inhibit cell proliferation, induce programmed cell death, suppress tumor growth, and modulate immune responses. While NSAIDs have been associated with potential benefits in cancer prevention, their use is not without risk. Long-term or high-dose NSAID use has been linked to gastrointestinal bleeding, ulcers, and perforation. Additionally, certain NSAIDs have been associated with an increased risk of cardiovascular events such as heart attack and stroke.
Physical activity: Regular exercise can reduce your risk of several types of cancer through a combination of physiological, hormonal, and immunological changes. It can reduce inflammation, improve immune function, improve hormonal regulation, and lower insulin levels. The American Cancer Society recommends engaging in at least 150 minutes of moderate activity or 75 minutes of vigorous activity each week. Furthermore, data indicates that individuals can see significant incremental benefit with additional exercise.
Water intake: Water intake plays a significant role in maintaining overall health, and has been shown to reduce the risk of bladder cancer. Adequate water intake helps dilute carcinogens, which reduces both the concentration of potential carcinogens and the time carcinogens spend in the bladder.
Fruit and vegetable consumption: Fruit and vegetables are rich in various nutrients which have been shown to have protective effects against multiple cancers. These foods contain a variety of antioxidants, which help neutralize free radicals in the body and reduce inflammation. Cruciferous vegetables in particular are associated with reduced risk of bladder cancer.[6]
Screening
Early detection of bladder cancer has a dramatic impact on prognosis. The 5-year survival rate for in situ cancer is over 96%, but drops to just 8% once the cancer has spread to distant parts of the body.
Depending on your age and risk factors, the optimal bladder cancer screening will vary:
Urinalysis: Checking for blood in the urine (or hematuria) can help detect some early stage bladder cancers. Urinalysis is usually performed as part of routine medical care. Blood in the urine can have many causes, and its presence during a urinalysis might lead to further testing. Any abnormal urinalysis results should always be interpreted by your doctor.
Urine tests for biomarkers: These tests look for evidence of tumor biomarkers in urine, a possible sign of bladder cancer. While these tests show promise, they are still imprecise, and aren’t recommended for average or low-risk individuals. They can be useful for individuals with other signs or symptoms of bladder cancers, or for detecting recurrence of cancer in individuals who have previously been diagnosed.
Self-monitoring: Most bladder cancers are found due to the appearance of common symptoms–such as blood in the urine, pain or difficulty urinating, or changes in the frequency of urination. While these symptoms can have many non-cancerous causes, it’s important to take them seriously. If you develop any of these symptoms, speak to your doctor to line up further testing.
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