Bladder Cancer: Symptoms, Causes, and Potential Treatments

Bladder cancer is responsible for 4% of all types of cancer diagnosed in the United States. The National Cancer Institute estimates 83,190 new cases of bladder cancer diagnosed in the United States in 2024. (26) 

Early detection of bladder cancer in its early stages dramatically improves prognosis. When bladder cancer is detected at stage 0, it has a 5-year relative survival rate of 97%. This drops to 8% if diagnosis occurs at stage 4. (7) 

Knowing and identifying the early symptoms of bladder cancer helps people seek prompt medical evaluation for better health outcomes.

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Understanding Bladder Cancer

Bladder cancer is a type of cancer that starts in the lining of the bladder, a hollow organ that stores urine. The bladder wall comprises several layers, each made of different cell types. Most bladder cancers start in the innermost lining of the bladder (called the urothelium or transition epithelium) and can grow into the deeper layers of the bladder wall. Over time, the cancer might spread outside the bladder into lymph nodes, bones, the lungs, or the liver. 

Bladder cancer generally affects people of older age; 90% of people diagnosed with bladder cancer are over the age of 55. It is the fourth most prevalent type of cancer in men, who are four times as likely to develop bladder cancer than women (4). 

Types of Bladder Cancer

There are different types of bladder cancer, named based on the type of cells in the bladder wall where the cancer originates (4, 39): 

• Transitional Cell Carcinoma (Urothelial Carcinoma): This is the most common type, accounting for 90% of all bladder cancers. This cancer begins in the transitional (urothelial) cells in the bladder's inner lining.
• Squamous Cell Carcinoma: This type accounts for 3-5% of bladder cancers in the United States. Squamous cells are thin, flat cells that line the inside of the bladder.
• Adenocarcinoma: This is a rare form of bladder cancer, accounting for only 1-2% of cases. Adenocarcinoma originates in the glands that line the bladder.
• Small Cell Carcinoma of the Bladder: Small cell carcinoma originates in nerve-like cells called neuroendocrine cells. This is an extremely rare type of cancer, affecting only about 1,000 people in the United States.
• Sarcoma: Rarely, bladder sarcomas originate in the bladder's muscle cells.

Early Bladder Cancer Symptoms

Blood in the urine, known as hematuria, is the most common sign of bladder cancer, with about 80-90% of bladder cancer patients experiencing this symptom. Hematuria can sometimes be seen with the naked eye (called "gross hematuria"), appearing as pink, red, or brown urine. In other cases, blood is only detectable under a microscope ("microscopic hematuria"). (10) 

While blood in the urine can result from other more benign conditions, it's important not to ignore it. Studies show that over one-third of people with visible blood in their urine and more than 10% of those with microscopic blood will be diagnosed with bladder cancer.

According to the Bladder Cancer Advocacy Network, women may experience delays in diagnosis compared to men because they are more likely to attribute hematuria to a gynecological problem.

Irritative bladder symptoms are also common, occurring in 20-30% of patients with bladder cancer. These include:

• Painful urination (dysuria)
• Urinary urgency
• Urinary frequency 

Advanced Bladder Cancer Symptoms

In addition to the above symptoms, patients with advanced disease can present with (3, 24): 

• Pelvic or bone pain
• Lower extremity edema (swelling), caused by compression of blood vessels that supply blood to and from the lower body
• Flank pain (located in the side of the body, below the rib cage and above the waist), caused by obstruction of the ureters (the tubes that carry urine from the kidneys to the bladder)
• Unexplained weight loss
• Fatigue

Bladder Cancer Symptom Variation Based on Tumor Type

Painless blood in the urine is the most common symptom of all types of bladder cancer, but other symptoms can vary depending on the type and stage of the cancer. Symptoms may differ based on whether the tumor is confined to the bladder's inner layers or has spread into the bladder muscle (non-muscle-invasive or muscle-invasive). (25, 34) 

Non-muscle-invasive bladder cancer (NMIBC) is found in the tissue that lines the bladder wall but has not infiltrated the bladder muscle. NMIBC is associated with increased urinary frequency, and larger tumors can lead to urgency and incontinence. (36) 

Muscle-invasive bladder cancer (MIBC), on the other hand, is more likely to present with symptoms related to advanced disease, such as lower back pain and pelvic pain due to local invasion. MIBC is also associated with a higher risk of distant metastases, which can lead to systemic symptoms depending on the organs involved. (5, 25, 34)

Histological variants of transitional cell carcinoma, such as micropapillary, plasmacytoid, and small cell variants, are associated with worse overall survival and may present with more aggressive symptoms. These variants often require more intensive treatment and have a poorer prognosis compared to typical urothelial carcinoma. (28) 

Risk Factors that May Influence Symptom Development

Bladder cancer risk factors include a combination of lifestyle, environmental, and genetic influences.

Smoking

Smoking is the primary risk factor for bladder cancer, with smokers facing a risk two to six times higher than non-smokers. This risk increases with both the length of time a person has smoked and the amount smoked, with ten pack-years often cited as a threshold for high risk. Over half of bladder cancer cases are found in former or current smokers. Additionally, smoking is associated with more aggressive forms of bladder cancer. (24) 

Toxic Exposures

People working in industries that handle aromatic amines – chemicals used in dyes, rubber, leather, and textiles – are at higher risk (2). 

Other occupations associated with an increased risk of developing bladder cancer due to exposure to bladder-irritating chemicals include:

• Painters
• Printers
• Firefighters
• Hairdressers
• Truck drivers 

Some research suggests that people who stay well-hydrated tend to have lower rates of bladder cancer. This may be because frequent urination helps flush chemicals out of the bladder, reducing the time these chemicals are in contact with the bladder lining. (1) 

Age and Gender

Bladder cancer is most common in older adults; the average age at diagnosis is 73. Men are more frequently diagnosed than women. However, when women are diagnosed, their cancers are often at a more advanced stage. (4) 

Genetics and Family History 

Bladder cancer risk is increased for individuals with a family history of bladder cancer in first- and second-degree relatives. This increased risk could be due to shared environmental exposures (8). 

Bladder cancer is generally not inherited (due to genes passed on from parent to child). Bladder cancer usually develops because of gene changes, called somatic mutations, that happen in bladder cells over a person's lifetime due to environmental factors like smoking or chemical exposure. (5) 

In rare cases, however, people may inherit a genetic syndrome that increases their risk for bladder cancer. Examples include:

• Retinoblastoma, caused by a mutation in the RB1 gene
• Cowden disease, caused by mutations in the PTEN gene
• Lynch syndrome, caused by a mutation in the MLHL, MSH2, MSH6, PMS2, or EPCAM genes

Chronic Inflammation

Chronic bladder inflammation from infections, urinary stones, or prolonged catheter use may also increase bladder cancer risk, especially for squamous cell carcinoma (8). 

Schistosomiasis, a parasitic infection, is linked to bladder cancer, specifically squamous cell carcinoma, due to the chronic inflammation and immune response triggered by parasite eggs deposited in the bladder wall. This leads to granuloma formation, tissue damage, and cellular changes that increase the risk of cancer development. The International Agency for Research on Cancer classifies Schistosoma haematobium infection as a group 1 carcinogen, indicating there is strong evidence it causes cancer in humans. (29, 35)  

When to Seek Medical Attention

Urinary symptoms are never normal. If you notice you have discolored urine, visit your doctor. You should also seek medical attention for other unexplained or worsening bladder discomfort or changes to urinary patterns.

Your doctor will order and perform a series of tests and imaging to diagnose bladder cancer, including (4, 21): 

• Urinalysis: Analysis of a urine sample
• Urine Cytology: Visualization of cells under a microscope
• Blood Work: Complete blood count (CBC) and comprehensive metabolic panel (CMP)
• Imaging: ultrasound, MRI, or CT (preferred) of the urinary tract
• Cystoscopy: A flexible camera is inserted into the bladder to examine the inside of the bladder directly. Cystoscopy should be performed in all patients with gross hematuria and those > 35 years with microscopic hematuria.
• Transurethral Resection of the Bladder Tumor (TURBT): A surgical procedure in which bladder tumors are removed from the bladder to diagnose, stage, and treat bladder cancer.

Bladder Cancer Symptom Overlap With Other Conditions

When a patient presents with symptoms that could indicate bladder cancer – such as hematuria, frequent urination, or painful urination – it's essential to consider a range of possible conditions that could be responsible for causing such symptoms, such as:

• Urinary tract infections (UTIs)
• Kidney stones
• Interstitial cystitis (painful bladder syndrome)
• Endometriosis
• Benign prostatic hyperplasia (BPH)
• Prostate cancer

Treatment Options After Symptom Recognition

There are five treatment options used to treat bladder cancer. The type of treatment recommended will depend on the stage and grade of the tumor at the time of diagnosis, as well as patient-specific factors like age, overall health, and personal preferences.

1. Surgery: Surgery is often the first-line treatment for bladder cancer, particularly in the early stages. Options include TURBT for removing non-muscle-invasive cancers or cystectomy (partial or complete removal of the bladder) for more advanced cancers. In some cases, lymph nodes and nearby organs may also be removed to prevent cancer spread.

2. Radiation Therapy: Radiation uses high-energy beams to kill cancer cells. It may be used as a primary treatment for those who cannot undergo surgery or as an adjunct therapy post-surgery to eliminate remaining cancer cells. Radiation can also be combined with chemotherapy to enhance its effectiveness.

3. Chemotherapy: Chemotherapy involves drugs that kill or stop the growth of cancer cells. It can be administered systemically for muscle-invasive or metastatic bladder cancer or directly into the bladder (intravesical) for early-stage tumors. It is often used in conjunction with surgery or radiation.

4. Immunotherapy: Immunotherapy boosts the body's immune system to help fight cancer. The most common form is intravesical Bacillus Calmette-Guérin (BCG) therapy, used to treat early-stage bladder cancer by stimulating an immune response within the bladder. 

5. Targeted Drug Therapy: Targeted therapies focus on specific proteins or genetic changes in cancer cells. Drugs such as erdafitinib, which targets FGFR gene mutations, or enfortumab vedotin, an antibody-drug conjugate, are used in certain advanced or recurrent bladder cancers, especially when other treatments don't work.

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Key Takeaways

• Recognizing early bladder cancer symptoms can be life-saving, as prompt diagnosis and treatment lead to significantly better health outcomes and survival rates. 
• If you experience any concerning urinary changes, such as blood in the urine, frequency, urgency, or pain with urination, consult a healthcare provider for evaluation.