Bladder Cancer: Causes, Symptoms and Treatment

What Is Bladder Cancer?

Bladder cancer is a malignant tumor that originates in the cells lining the urinary bladder. The most common type is urothelial carcinoma (formerly transitional cell carcinoma), which arises from the urothelial cells that form the inner lining of the bladder wall. Less common types include squamous cell carcinoma and adenocarcinoma. Bladder cancer is among the ten most common cancers worldwide and is significantly more prevalent in men than in women.

Causes and Risk Factors

The development of bladder cancer is associated with a range of risk factors:

• Smoking: Tobacco use is the single most important risk factor, responsible for approximately 50% of all cases. Carcinogens from tobacco smoke are excreted in the urine and come into direct contact with the bladder lining.
• Chemical exposure: Occupational exposure to aromatic amines (e.g., in the dye, rubber, and leather industries) significantly increases the risk.
• Chronic bladder irritation: Recurrent urinary tract infections or bladder stones can increase long-term cancer risk.
• Age and sex: Risk increases with age, and men develop bladder cancer approximately three to four times more often than women.
• Genetic factors: A family history of bladder cancer may increase individual risk.
• Prior pelvic radiation therapy: Previous radiation treatment to the pelvic area can increase the risk of developing bladder cancer.

Symptoms

The most characteristic and common symptom of bladder cancer is painless blood in the urine (hematuria). This can be visible to the naked eye (gross hematuria) or detectable only under a microscope (microscopic hematuria). Other possible symptoms include:

• Frequent urination (urinary frequency)
• Burning or pain during urination (dysuria)
• Lower abdominal or flank pain
• Back pain (in advanced stages)
• Unexplained weight loss and fatigue (in metastatic disease)

Because hematuria can also result from other conditions, prompt medical evaluation is strongly recommended.

Diagnosis

Several diagnostic methods are used to detect and evaluate bladder cancer:

• Urine tests: Detection of blood in the urine and cytological examination for cancer cells (urine cytology).
• Ultrasound: An initial imaging method used to assess the bladder.
• Cystoscopy: The gold standard for diagnosis. A thin instrument is inserted through the urethra to directly visualize the bladder wall and collect tissue samples (biopsies).
• Transurethral resection of bladder tumor (TURBT): Endoscopic removal of the tumor for histological analysis and staging.
• Imaging studies: CT (computed tomography) or MRI (magnetic resonance imaging) of the abdomen and pelvis to assess tumor extent and detect possible metastases.

Staging and Classification

Bladder cancer is staged using the TNM classification system. The key distinction is:

• Non-muscle-invasive bladder cancer (NMIBC): The tumor is confined to the inner lining and submucosa of the bladder (stages Ta, T1, Tis). This accounts for approximately 75% of newly diagnosed cases.
• Muscle-invasive bladder cancer (MIBC): The tumor has grown into the muscular wall of the bladder (stage T2 and beyond). This form carries a worse prognosis.

Treatment

Non-Muscle-Invasive Bladder Cancer

For non-muscle-invasive disease, transurethral resection (TURBT) is performed to remove the visible tumor. Depending on the risk group, this is followed by intravesical therapy -- the direct instillation of medication into the bladder:

• Chemotherapy agents (e.g., Mitomycin C) to reduce the risk of recurrence
• BCG immunotherapy (Bacillus Calmette-Guerin): Instillation of weakened tuberculosis bacteria to stimulate the immune system against tumor cells -- particularly effective for high-risk tumors

Muscle-Invasive Bladder Cancer

For muscle-invasive tumors, the following treatment options are available:

• Radical cystectomy: Surgical removal of the entire bladder (along with the prostate in men, or the uterus and ovaries in women). This is considered the standard treatment.
• Neoadjuvant chemotherapy: Chemotherapy administered before surgery to shrink the tumor and improve outcomes.
• Bladder-sparing therapy: In selected patients, a combination of TURBT, chemotherapy, and radiation therapy may be offered as an alternative to cystectomy.
• Immunotherapy (checkpoint inhibitors): Agents such as pembrolizumab or atezolizumab are used for metastatic or platinum-refractory bladder cancer.
• Targeted therapy: Newer targeted agents (e.g., FGFR inhibitors such as erdafitinib) are available for tumors with specific genetic alterations.

Prognosis

Prognosis depends strongly on the stage at diagnosis. Non-muscle-invasive cancers have a relatively favorable prognosis; however, the recurrence rate is high (up to 70% within five years), making regular follow-up cystoscopy essential. Muscle-invasive and metastatic forms have significantly lower five-year survival rates.

Prevention and Early Detection

Since smoking is the leading risk factor, not smoking is the most effective preventive measure. Reducing occupational exposure to carcinogenic chemicals is equally important. Painless blood in the urine should always be evaluated promptly by a physician, as early diagnosis substantially improves treatment options and overall prognosis.

References

1. Babjuk M. et al. - EAU Guidelines on Non-muscle-invasive Bladder Cancer. European Association of Urology (2023). Available at: uroweb.org
2. Witjes J.A. et al. - EAU Guidelines on Muscle-invasive and Metastatic Bladder Cancer. European Association of Urology (2023). Available at: uroweb.org
3. National Cancer Institute (NCI): Bladder Cancer Treatment (PDQ) - Health Professional Version (2024). Available at: cancer.gov