The urinary bladder is a part of the urinary system. It is a muscular, hollow organ that stores the urine produced by the kidneys. Several types of cells are present in the bladder. These include urothelial cells, squamous cells, and epithelial cells. Abnormal growth and division in one or more of these bladder cells result in tumor formation, and this condition is known as bladder cancer or bladder tumor. A bladder tumor most commonly occurs in the cells present in the internal lining of the bladder. In most cases, this cancer type is diagnosed in the early stages, and therefore, the treatment outcomes are usually good.
Men have a higher chance of developing urinary bladder cancer than women. It has been reported that the lifetime chances in men for developing bladder tumors are 1 in 28, while in women, it is 1 in 91. Bladder carcinoma ranks sixth in the list of most common cancers in men and seventeenth in the list of most common cancers in women.
The common types of bladder cancer are:
Urothelial bladder carcinoma was previously called transitional carcinoma. It is the most common form of bladder cancer and accounts for 90% of all bladder carcinomas. It initiates in the urothelial cells. These cells form the internal lining of the urinary bladder. Urothelial cells are also present at other sites of the urinary tract, such as urethra and ureters. People with urothelial cancer may have tumors at these sites, and therefore, doctors usually examine the complete urinary tract in patients.
Squamous cells are flat, thin cells present on the lining of the bladder. Squamous cell carcinoma of the bladder includes about 5% of all bladder carcinomas. People with chronic inflammation or bladder irritation have a higher risk for squamous cell carcinoma of the bladder. Squamous cell carcinoma is more prevalent in geographic areas where parasite-associated bladder infections (schistosomiasis) are common.
This is a rare type of bladder carcinoma, and it forms in the neuroendocrine cells. They account for less than 2% of all bladder carcinomas. This cancer generally grows rapidly and should be promptly treated with chemotherapy.
Adenocarcinoma of the bladder is a rare cancer that accounts for 1 to 2% of all bladder carcinomas. Adenocarcinoma develops in the mucus-secreting glandular cells of the urinary bladder. Patients with chronic inflammation or irritation of the urinary bladder have a higher risk of developing adenocarcinoma.
Sarcoma in the bladder initiates in the muscular wall of the bladder. It is a rare cancer of the urinary bladder.
It includes carcinoma in situ and non-invasive papillary carcinoma. Non-invasive papillary carcinoma does not grow into deeper layers, and it can be easily removed. Carcinoma in situ grows only on or near the bladder surface.
Non-muscle-invasive bladder lesion does not grow into the muscle but affects the lamina propria.
Muscle-invasive bladder lesions grow into the muscles and sometimes spread to fatty tissues.
The urinary bladder cancer staging is as follows:
It is divided into two stages - stage 0a and stage 0is. Stage 0a is noninvasive papillary carcinoma. It may be low-grade or high-grade, depending on the characteristics of the cancer cells under the microscope. Stage 0is is carcinoma in situ, and in most cases, it is a high-grade tumor characterized by a flat tumor on the inner lining of the bladder.
In stage 1 bladder cancer, the cancer invades the connective tissue below the inner lining of the urinary bladder. The cancer has not spread to the muscle wall of the bladder. Further, the cancer has not spread to the nearby lymph nodes or distant organs.
In stage 2 bladder cancer, the cancer spreads through the connective tissue and invades the muscular wall. However, it has not completely invaded the muscle layer to reach the fatty tissue present below it. Further, the cancer has not spread to the nearby lymph nodes or distant organs.
Stage 3 bladder cancer is divided into stages 3a and 3b. In stage 3a of bladder carcinoma, the cancer has completely invaded the muscle layer and reached the fatty layer surrounding the bladder. The cancer may also have spread to the prostate and seminal vesicles in men or to the vagina and uterus in women. However, it has not reached the abdominal wall, lymph nodes, or distant organs. In stage 3b bladder carcinoma, the cancer has invaded the lining, muscular wall, connective tissue, and fatty tissues and spread to >2 lymph nodes.
Stage 4 bladder cancer is divided into two sub-stages. Stage 4a bladder carcinoma has invaded the abdominal wall and the pelvis. However, it may or may not have spread to the lymph nodes. It may not have spread to distant organs. Stage 4b bladder carcinoma may or may not have invaded the nearby abdominal cavity organs and lymph nodes. It has spread to one or more distant organs, such as the lungs, bones, and liver.
Bladder cancer causes various symptoms. Most of these symptoms overlap with those of other serious and less serious health conditions. It is, therefore, important to see a doctor for a conclusive diagnosis.
Bladder cancer is a polygenic condition resulting from several environmental factors and various low-penetrance predisposition genes. Mutations in several genes, such as FGFR3, KDM6A, PIK3CA, and TP53, may result in bladder cancer. A family history of bladder cancer may also increase the risk of bladder cancer.
Some of the common bladder cancer symptoms are:
Patients with bladder cancer may have hematuria, or blood in the urine, which is one of the stage 1 bladder cancer symptoms. In most cases, blood in urine is generally one of the first signs of bladder cancer. The patients may experience very little or no pain while passing urine with blood in it.
It is important to note that there are several reasons for the presence of blood in urine other than bladder cancer, such as infection or bladder stones. However, patients should consult with a doctor to rule out serious conditions.
Recurrent bladder infections may be one of the early symptoms of bladder cancer. It is because the tumor interferes with the protective lining of the bladder to allow the cancer cells to evade the immune system.
Patients with bladder cancer may experience various problems related to urination. This is also one of the bladder problem symptoms, which can be caused by various other urological conditions; therefore, it is important to see a doctor for a definitive diagnosis. Some of them are:
The presence of cancer cells in the bladder can cause irritation, and therefore, patients with bladder cancer experience frequent urination, even when the bladder is not filled.
Pain or a burning sensation during urination is termed dysuria, and it may be one of the bladder cancer symptoms.
The tumor in the bladder may partially or completely block the flow of urine and interfere with the ability of the patient to urinate.
Some patients with bladder cancer experience an urge to urinate, especially at night. It may occur when the cancer affects the bladder muscles and reduces the bladder's ability to store urine.
Patients with bladder cancer may also have a weak urine system, which is caused when the tumor presses on the bladder muscle or when the tumor growth blocks the urine flow.
Pain in the pelvis is one of the bladder cancer symptoms observed in the advanced stages. Patients may initially have pain in the pelvic region, but later, it radiates to the lower back. It usually occurs on one side of the pelvis but may be present centrally. Pelvic pain occurs when the cancer spreads beyond the bladder.
Weight loss and reduced appetite are also identified as important bladder cancer symptoms. Compared to people with early-stage bladder cancer, people with metastatic and advanced cancer are more likely to lose weight and appetite.
A complete or partial loss of appetite may also be a sign of bladder cancer. As the disease spreads to other organs in the body, the appetite for food is affected.
Swelling in the ankles and feet may occur in patients with advanced-stage bladder cancer. The swelling develops when the cancer spreads to the lymph nodes and interferes with lymph drainage. The condition is known as lymphedema.
The exact pathophysiology of bladder cancer is not known. However, some of the possible bladder cancer causes are:
Smoking cigarettes is one of the most important risk factors for bladder cancer. Almost half of bladder cancers are probably due to smoking cigarettes. This is because the chemicals present in the cigarette are excreted in urine. These carcinogens interfere with the bladder's protective lining and increase the bladder cancer risk.
Previous radiation therapy sessions for treating other cancers of the pelvic region may also become one of the possible bladder cancer causes. Radiation damages the bladder lining and causes radiation cystitis.
Besides exposure to carcinogens present in cigarettes, exposure to other chemicals may also cause bladder cancer. These include aromatic amines used in the dye industry, such as beta-naphthylamine and benzidine.
Chronic and frequent infections of the bladder may also cause bladder cancer. People with a history of frequent bladder cancer, especially with three or more infections, are at increased risk for bladder cancer.
Studies have reported that long-term use of catheters may cause bladder cancer, as these people are prone to frequent infections. The risk is higher for people between the ages of 45 and 60.
Pioglitazone, used for managing diabetes, may cause bladder cancer in a time- and dose-dependent manner. It is important to monitor patients on long-term pioglitazone for bladder cancer.
It is important for patients to not ignore any symptoms of concern, especially if they have higher chances of developing bladder cancer. They should consult oncologists when they experience sudden changes or challenges with urination, blood in urine, loss of appetite, fatigue, and weight loss.
If an individual is suspected of having bladder cancer, the specialists will begin with a physical examination and medical history assessment to understand the cause of the symptoms. If the observations are alarming, additional tests may be recommended. The commonly recommended tests for the diagnosis of bladder cancer include:
The patient undergoes a detailed physical evaluation to identify the causes of their symptoms. The doctor may inquire about the symptoms experienced. The severity of symptoms is also evaluated to get more information about the underlying causes. The physical examination includes a digital rectal examination and a pelvic examination (in the case of women).
The doctor may also inquire about the medical and family history of the patients to determine the risk of bladder cancer. The social and occupational history of the patients, such as smoking and chronic exposure to toxic substances, is also examined to detect risk factors for bladder cancer. If the doctor suspects bladder cancer or other serious medical conditions, the patients are recommended for further tests.
Analysis of the urine provides vital information about the health of the kidney and bladder. During urinalysis, the doctors determine the content, characteristics, and concentration of various substances in urine. Chemical, physical, and microscopic evaluations are performed under urinalysis. The presence of occult blood is also determined during urine evaluation. The chemical evaluation involves qualitative and quantitative determination of red blood cells, glucose, white blood cells, urobilinogen, proteins, bilirubin, leukocyte esterase, ketone bodies, and nitrites. Urine culture tests are also performed to detect the presence of a urine infection.
Several imaging tests are done to determine the presence and extent of cancer. These imaging tests include:
Doctors advise the patients to undergo cystoscopy if they suspect that they have any problems with the bladder. Cystoscopy is performed with the assistance of a cystoscope. A cystoscope is a thin, long tube with a camera at the end. The doctor inserts the cystoscope into the urethra to reach and examine the bladder. The images of the internal tissues of the bladder are transmitted on the screen. The doctor evaluates these images and determines if there is any problem with the bladder.
A CT scan of the bladder, ureters, and kidney is known as a CT urogram. It provides clear images of the organs of the urinary tract. A CT scan offers detailed information about the shape, size, presence, and site of tumors in the bladder. The detailed CT examination of the abdominal area determines the spread of cancer to the lymph nodes, pelvis, and other regions of the abdominal cavity.
A biopsy is a confirmatory test recommended for the diagnosis of bladder cancer. The procedure involves taking samples of the abnormal tissues through a needle or surgery and examining the sample under a microscope to find malignant cells.
Transurethral resection of bladder tumors is the method for performing a bladder biopsy. During this procedure, the doctor obtains the abnormal tissues of the bladder and some surrounding healthy tissues. The sample is evaluated under the microscope. If the presence of cancer is confirmed, the doctors also test to see if the cancer has invaded the bladder muscles.
Urine cytology is a method to detect the presence of cancer cells in urine, and it is one of the commonly recommended tests for the diagnosis of bladder cancer. This test helps in diagnosing cancers of the kidney, ureter, prostate, and urinary bladder. The pathologists evaluate the urine sample under the microscope to detect cancer cells in the urine.
Once bladder cancer is diagnosed, the next step is to determine the type and stage of the cancer. It assists the oncologists in optimizing the treatment strategy. Some bladder cancer types are rapidly progressive and require aggressive treatment. The imaging tests recommended for bladder cancer staging include a CT scan, magnetic resonance imaging, PET scan, and ultrasound for bladder cancer. A chest X-ray is also performed to determine the spread of cancer to the lungs.
An intravenous pyelogram involves examining the organs of the urinary system with the help of X-rays. Before the procedure, a special dye is administered intravenously. The dye travels to the kidneys through the bloodstream, where it is filtered. This dye later gets collected in different organs of the urinary system.
The X-ray radiation tracks the movement of the dye. The dye outlines the internal tissues of these organs and provides information about the presence of any abnormal masses.
If the patients diagnosed with bladder cancer complain about bone-related symptoms, such as bone pain, the oncologists may recommend they undergo a bone scan. It helps in detecting the spread of cancer to the bones.
Specialists also recommended specific molecular tests for the diagnosis of bladder cancer. These tests look for specific molecular tumor markers in the urine and blood samples. These include detecting and determining the levels of prostate-specific antigen, carcinoembryonic antigen, HCG, alpha-fetoprotein, prostatic acid phosphatase, lactate dehydrogenase, and CA-125.
Bladder cancer will often need a comprehensive treatment approach, wherein the multidisciplinary clinical team will thoroughly study the diagnosis, understand the patient’s overall condition, and thereafter devise a personalized treatment plan. The following procedures are commonly recommended for the treatment of bladder cancer:
Surgery is usually the first line of bladder tumor treatment and is the only treatment used if the cancer is localized and limited to the bladder. The type of surgery depends on the stage and extent of bladder cancer. The types of surgeries are:
Partial cystectomy is a bladder cancer surgery that involves the removal of the damaged portion of the bladder. The procedure is usually recommended for early-stage bladder cancers. The remaining bladder is still functional.
Radical cystectomy is a bladder cancer surgery that removes the complete urinary bladder. This surgery is performed in cases where cancer spreads to a significant portion of the bladder, usually during the advanced stage of the disease. Radical cystectomy in men also involves the removal of seminal vesicles, the prostate, and the bladder. In women, the ovaries, fallopian tubes, uterus, and a portion of the vagina are also removed along with the bladder during radical cystectomy.
TURBT is a bladder cancer surgery that is both diagnostic and therapeutic. It is performed to remove tumors limited to the inner layer of the bladder (early-stage bladder cancer) that have not invaded the bladder's muscle wall.
Neobladder reconstruction is the procedure performed after radical cystectomy to create a new route for urine drainage. A piece of intestine is taken to form a sphere-shaped reservoir, which functions as a bladder.
Chemotherapy is a bladder cancer therapy for treating bladder cancer that uses bladder cancer medications to kill cancer cells. Chemotherapy for bladder cancer may be administered intravenously or orally.
It is usually used in combination with surgery or radiation therapy. When used before surgery, it is known as neoadjuvant therapy, and it helps shrink the tumor size. When used after surgery, it is known as adjuvant therapy, and it helps destroy the residual cancer cells.
Radiation therapy is a bladder tumor treatment that involves using high-energy ionizing radiation to destroy cancer cells. It may be administered in combination with surgery or chemotherapy. It may also be recommended for advanced bladder cancer treatment and as a part of palliative care to minimize cancer symptoms. External beam radiation therapy is commonly used to treat bladder cancer.
Immunotherapy is bladder cancer therapy that uses drugs to strengthen the patient's immune system to detect and kill cancer cells. Immunotherapy drugs interfere with the specific pathways of cancer cells that allow them to hide from the immune system. Several classes of drugs are used in immunotherapy, such as immune checkpoint inhibitors and PD-1 and PD-L1 inhibitors.
Certain biomolecules and pathways are present specifically in cancer cells, and these allow their uncontrolled division and proliferation. Targeted therapy is a bladder tumor treatment that targets these molecules and pathways and affects the growth of cancer cells. This treatment helps delay the disease progression and prolong survival. The classes of drugs used include antibody-drug conjugates and FGFR inhibitors.
This treatment of bladder cancer involves delivering the drug directly into the bladder. Immunotherapy and chemotherapy drugs can be administered through this approach. It treats non-muscle invasive bladder cancer and higher-stage, invasive bladder cancers. The therapy is used in combination with radiation therapy and surgery.
Bladder cancer patients who have exhausted all standard treatment options may enroll in clinical trials related to bladder cancer management. These clinical trials test new treatments, diagnostic tests, and interventions to detect, prevent, and treat bladder cancer. Enrolling in clinical trials helps patients access new bladder tumor treatments before they become widely available.
A few lifestyle-related and non-lifestyle-related factors have been identified as bladder cancer risk factors, i.e., being associated with these factors can increase one’s risk of developing bladder cancer. These risk factors do not guarantee a bladder cancer diagnosis and, therefore, are the possible causes of bladder cancer.
It is not possible to achieve 100% bladder cancer prevention as the exact cause is not known. That said, certain measures can reduce its risk and support its early detection.
Some of the bladder cancer risk factors are:
Cigarette smoking is one of the most common urinary bladder cancer risk factors. Several studies have reported the association between smoking and an increased incidence of bladder cancer. It has been found that people who smoke have a 4- to 7-fold higher risk of developing bladder cancer than people who do not smoke. Carcinogens present in tobacco are excreted through urine. In this way, these carcinogens disrupt the inner lining of the bladder.
Although bladder cancer can occur in people of any age group, it most commonly occurs in the elderly. It has been found that about 90% of the cases of bladder cancer occur in people over the age of 55. The average age for the diagnosis of bladder cancer is 73 years.
Gender also affects the incidence of bladder cancer. Men are at increased risk of developing bladder cancer. However, bladder cancer in women is diagnosed at a later stage than in men. It is common for bladder cancer to be misdiagnosed or diagnosed in later stages among women. The possible reasons for a higher incidence of bladder cancer in men may be a higher rate of tobacco use and exposure to industrial chemicals.
Race and ethnicity also affect the incidence of bladder cancer. Researchers have performed several studies to determine the incidence of bladder cancer in people of different races and ethnicities. It has been reported that white people are at increased risk of developing bladder cancer compared to people of other ethnicities. Survival from bladder cancer also has disparities based on race and ethnicity. The best survival rate is reported in Hispanic whites, while the worst survival rate is seen in blacks.
A medical and family history of bladder cancer increases the risk of developing this condition. Those with a father, child, or sibling diagnosed with bladder cancer have an increased likelihood of developing bladder cancer. However, bladder cancer rarely occurs in families. Underlying medical conditions in the family, such as Lynch syndrome, also increase the risk of developing bladder cancer.
Chronic exposure to certain chemicals, such as those used in manufacturing dyes, paints, textiles, and leather, increases the risk of bladder cancer. Due to the chronic inhalation of diesel fumes, truck drivers are also at increased risk of bladder cancer. These chemicals are filtered by the kidneys from the blood and pass through the ureters to the bladder. These chemicals stay in the bladder for some time and disrupt the internal lining. Disruption of the bladder lining for a long period increases the risk of bladder cancer.
Chronic irritation and bladder infections also increase the likelihood of developing bladder cancer. Chronic irritation may be due to underlying medical conditions, such as bladder stones or the chronic use of catheters. It has been reported that people living in areas with a high incidence of parasitic infection of the bladder have a higher risk of developing squamous cell cancers of the bladder.
People taking a diet devoid of fruits and vegetables are at increased risk for bladder cancer. A study has reported that a higher intake of a pro-inflammatory diet increases the risk of several cancers, including kidney, prostate, and bladder cancer. It has also been found that the Mediterranean diet has a preventive effect, and the Western diet has a detrimental effect on bladder cancer risk.
Several treatment strategies for managing previous cancer also increase the risk of bladder cancer. For instance, using cyclophosphamide as a chemotherapy drug enhances bladder cancer risk. Further, radiation therapy for treating cancers of the pelvic region also increases bladder cancer risk.
“How to prevent bladder cancer?” is one of the most common questions asked. Although it is not possible to prevent this cancer, one can reduce its risk. Following are some bladder cancer prevention tips:
Quitting smoking is one of the most important preventive measures, and it can increase the chances of bladder cancer prevention. A recent study has reported that the risk of bladder cancer in smokers is higher than what was thought before. Therefore, it is important to refrain from smoking.
Drinking plenty of fluid may help reduce the risk of bladder cancer, especially in people exposed to toxic chemicals. Drinking a significant amount of fluid helps flush out the chemicals from the bladder.
People should eat a healthy diet to prevent bladder cancer. The diet should have fruits and vegetables. It helps the body fight against abnormal and mutated cells.
It is necessary to avoid chronic exposure to toxic chemicals. It is important for people working in the textile, leather, dye, and paint industries to follow safety instructions. Hairdressers should also avoid long-term exposure to hair dyes. Truck drivers should also avoid chronic exposure to diesel fumes.
People, especially those with family and medical histories of bladder cancer, chronic bladder infections, and smoking habits, should undergo regular check-ups to detect bladder cancer early.
Bladder cancer is a form of cancer that develops in the urinary bladder. The different types of bladder cancer include squamous cell carcinoma, urothelial carcinoma, small cell carcinoma, and adenocarcinoma. Stage 0 and stage 1 bladder cancers are categorized as early-stage or initial-stage cancers, and stage 4 bladder cancer is referred to as advanced-stage cancer.