Bladder Cancer: Symptoms, Types, Causes and Treatment

Bladder cancer is a common and complex disease with a significant impact on patients’ lives and public health worldwide. Its presentation can be subtle, its causes multifactorial, and its management rapidly evolving with advances in science and medicine. This article provides a comprehensive, evidence-based overview of bladder cancer, focusing on its symptoms, types, causes, and treatment options. Whether you are a patient, caregiver, or simply interested in learning more, this guide will help you understand the critical aspects of this disease.

Symptoms of Bladder Cancer

Recognizing the signs and symptoms of bladder cancer is crucial for early detection and improved outcomes. Most people with bladder cancer initially experience symptoms that can be mistaken for less serious urinary problems. Understanding these signs can prompt timely investigation and potentially life-saving intervention.

Symptom	Description	Frequency/Significance	Source(s)
Haematuria	Blood in urine (visible/invisible)	Most common symptom (>80%)	1 2 3 4 5
Dysuria	Painful or burning urination	Less common, may mimic UTI	2 3 4
Urinary Frequency/Urgency	Needing to urinate often/suddenly	Occasional, may mimic infection	2 4 5
Abdominal/Flank Pain	Pain in lower abdomen or sides	Usually late, rare, signals advanced disease	2 3 5

Table 1: Key Symptoms

Haematuria: The Cardinal Warning Sign

The most common and significant symptom of bladder cancer is haematuria—blood in the urine. This may be visible (macroscopic/gross haematuria) or detected only by laboratory testing (microscopic haematuria). Painless visible haematuria is present in over 80% of cases and is the strongest predictor of bladder cancer in primary care settings 1 2 3 5. In men aged 55–74, the positive predictive value (PPV) of visible haematuria for bladder cancer reaches 7.1% 5.

It is important to note that while haematuria is the hallmark symptom, it can also be caused by benign conditions. Nevertheless, its presence—especially if persistent—always warrants prompt medical evaluation.

Irritative Urinary Symptoms

Some patients experience symptoms resembling a urinary tract infection, such as:

• Dysuria (painful urination)
• Increased urinary frequency
• Urgency to urinate

These symptoms are less common than haematuria but may be the primary complaint, particularly in early-stage or non-muscle-invasive bladder cancer. Irritative symptoms are more often seen in carcinoma in situ or high-grade tumors and can lead to misdiagnosis as infection, delaying the correct diagnosis 2 3 4 5.

Less Common Symptoms: Pain and Other Signs

Pain, such as lower abdominal, pelvic, or flank pain, is rare at presentation and typically indicates more advanced or metastatic disease 2 3 5. Additional non-specific symptoms like urinary tract infections, raised inflammatory markers, constipation, or elevated creatinine may be associated but have low predictive value for bladder cancer 3.

When to Seek Medical Advice

Anyone experiencing unexplained or persistent haematuria—especially painless and visible blood in the urine—should seek prompt evaluation. Similarly, persistent urinary symptoms without clear infection should be investigated, particularly in older adults or those with risk factors.

Types of Bladder Cancer

Bladder cancer is not a single disease but encompasses several types, each with distinct biological behavior, prognosis, and treatment approaches. Understanding these types is essential for tailoring therapy and predicting outcomes.

Type/Subtype	Key Features	Prevalence/Notes	Source(s)
Urothelial (Transitional cell) carcinoma	Arises from urothelium lining; most common	~90% of cases	10 13 14
Non-muscle-invasive (NMIBC)	Confined to mucosa/submucosa; often papillary	~70% at diagnosis	1 2 10 13
Muscle-invasive (MIBC)	Invades muscular layer; higher risk	~30% at diagnosis	1 2 13
Squamous cell carcinoma	Associated with chronic irritation/infection	3–5%; common in schistosomiasis regions	12 14 15
Adenocarcinoma	Glandular differentiation	Rare (~2%)	13 14
Molecular subtypes	Luminal, Basal/Squamous, Neuroendocrine-like, etc.	Vary in prognosis and therapy	6 7 9

Table 2: Main Types and Subtypes

Urothelial (Transitional Cell) Carcinoma

This is by far the most prevalent form of bladder cancer, accounting for about 90% of cases in industrialized countries. It arises from the urothelial lining of the bladder and can present as either non-muscle-invasive or muscle-invasive disease 10 13 14.

Non-Muscle-Invasive vs. Muscle-Invasive

• Non-Muscle-Invasive Bladder Cancer (NMIBC):

  • Includes papillary tumors confined to the mucosa (Ta), lamina propria (T1), or carcinoma in situ (CIS).
  • Tends to recur but is generally not immediately life-threatening 1 2 10 13.
  • About 70% of newly diagnosed cases are NMIBC.

• Muscle-Invasive Bladder Cancer (MIBC):

  • Tumor invades the muscular layer of the bladder wall.
  • Associated with a higher risk of metastasis and mortality 1 2 13.
  • Accounts for approximately 30% of cases at diagnosis.

Non-Urothelial Bladder Cancers

• Squamous Cell Carcinoma:

  • Linked to chronic irritation, infection, or schistosomiasis (notably in parts of Africa and the Middle East) 12 14 15.
  • Makes up 3–5% of bladder cancers in developed countries, but up to 75% in schistosomiasis-endemic regions.

• Adenocarcinoma:

  • Rare, accounting for about 2% of cases 13 14.

Molecular Subtypes: The New Frontier

Recent advances have revealed that both NMIBC and MIBC can be further classified into molecular subtypes with differing genetic alterations, responses to therapy, and prognoses 6 7 9. Examples include:

• Luminal Subtypes: Often linked to FGFR3 mutations; generally better prognosis.
• Basal/Squamous Subtypes: More aggressive, enriched in RB1 and NFE2L2 alterations.
• Neuroendocrine-like: Rare but highly aggressive 6 7 9.

Understanding these molecular classes is paving the way for more personalized treatment strategies.

Causes of Bladder Cancer

Bladder cancer is a multifactorial disease, with both environmental and genetic contributors. Identifying and understanding these risk factors is key to prevention and early detection.

Cause/Risk Factor	Description	Strength of Evidence/Impact	Source(s)
Tobacco smoking	Carcinogens in cigarettes excreted in urine	Strongest, accounts for ~50% of cases	11 12 13 14 15
Occupational exposures	Aromatic amines (dye, rubber, leather industries)	Well-established	12 14 15
Chronic infection/irritation	Schistosoma haematobium, catheters, stones	High risk for SCC	12 14 15
Medications/chemicals	Cyclophosphamide, phenacetin, arsenic	Moderate to strong	12 14 15
Radiation	Pelvic radiotherapy history	Increased risk	14 15
Genetic susceptibility	NAT2, GSTM1, KDM6A gene variants	Modest risk	12 8 9
Diet/lifestyle	Fruits/vegetables protective, high-fat/pork may increase risk	Weaker evidence	12 15

Table 3: Major Causes and Risk Factors

Tobacco Smoking: The Dominant Risk Factor

Cigarette smoking is the most significant risk factor for bladder cancer worldwide. Carcinogenic substances in tobacco smoke are filtered by the kidneys and excreted in urine, exposing the bladder lining to DNA-damaging agents. Smoking accounts for about half of bladder cancer cases in men and a third in women 11 12 13 14 15. Risk increases with the duration and intensity of smoking and decreases after cessation, although never returns to baseline 15.

Occupational and Environmental Exposures

Certain occupations involving exposure to aromatic amines and other chemicals—such as dye, rubber, leather, paint, and aluminum industries—have a higher risk of bladder cancer 12 14 15. Regular exposure can double or even quintuple risk, making workplace safety essential.

Other notable exposures include:

• Long-term use of cyclophosphamide (a chemotherapy) or phenacetin-containing analgesics
• Chronic arsenic exposure in drinking water (notably in Argentina, Chile, and Taiwan) 14 15

Chronic Irritation and Infection

Chronic irritation of the bladder, whether from long-term catheter use, bladder stones, or repeated infections, can increase cancer risk. In developing countries, especially in Africa and the Middle East, infection with Schistosoma haematobium is a major cause of squamous cell carcinoma of the bladder 12 14 15.

Genetic and Dietary Factors

While most cases are linked to environmental causes, certain genetic variants (e.g., NAT2 slow acetylator, GSTM1 null, KDM6A mutations) can modestly increase risk 8 9 12. Diets rich in fruits and vegetables may offer some protection, while high intake of red meat and fat may slightly elevate risk, though evidence here is weaker 12 15.

Other Factors

• Radiation: Previous radiotherapy to the pelvis (e.g., for uterine cancer) increases risk 14 15.
• Gender and Age: Men are three times more likely than women to develop bladder cancer, with most cases occurring after age 65 2 12 15.

Treatment of Bladder Cancer

Bladder cancer treatment is highly individualized, reflecting disease stage, tumor biology, patient health, and preferences. Modern management involves a multidisciplinary approach and continues to evolve with advances in surgery, drug therapy, and molecular medicine.

Treatment Modality	Indication/Use Case	Key Points	Source(s)
Transurethral resection (TURBT)	Initial removal of bladder tumor	Gold standard for diagnosis & NMIBC	1 10 13 16 18
Intravesical therapy (BCG/chemo)	High-risk NMIBC, CIS	BCG is mainstay; reduces recurrence	1 10 13 16 18
Radical cystectomy	Muscle-invasive or refractory NMIBC	Removes bladder, requires urinary diversion	1 10 13 16
Bladder preservation (trimodal)	Selected MIBC patients	Combines TURBT, chemo, radiation	1 10 16 17
Systemic chemotherapy	MIBC, metastatic disease	Platinum-based, neoadjuvant/adjuvant	1 10 16 17
Immunotherapy	Advanced/metastatic, BCG-refractory	Checkpoint inhibitors, durable in some	10 16 17 19
Targeted therapy	Patients with actionable mutations	FGFR inhibitors, antibody-drug conjugates	10 17 19

Table 4: Main Treatment Approaches

Management of Non-Muscle-Invasive Bladder Cancer (NMIBC)

• Transurethral Resection of Bladder Tumor (TURBT): This endoscopic procedure is both diagnostic and therapeutic for NMIBC 1 10 13 16 18.
• Intravesical Therapy: After TURBT, high-risk patients receive medications directly into the bladder, most commonly Bacillus Calmette–Guérin (BCG) or chemotherapy. BCG is the gold standard to reduce recurrence and progression for intermediate and high-risk NMIBC 1 10 13 16 18.
• Enhanced Surveillance: Due to high recurrence rates, patients require regular cystoscopy and urine testing 10 13 18.

Management of Muscle-Invasive Bladder Cancer (MIBC)

• Radical Cystectomy: Surgical removal of the bladder (and prostate/uterus in men/women) with reconstruction or diversion of urine is the mainstay for localized MIBC or high-risk NMIBC failing BCG 1 10 13 16.
• Bladder Preservation (Trimodal Therapy): In select patients, a combination of maximal TURBT, chemoradiation, and close surveillance can offer outcomes comparable to surgery while preserving the bladder 1 10 16 17.
• Neoadjuvant/Adjuvant Chemotherapy: Platinum-based systemic chemotherapy before or after surgery improves survival in MIBC 1 10 16 17.

Treatment of Advanced and Metastatic Disease

• Systemic Chemotherapy: Historically, cisplatin-based regimens have been standard for metastatic disease, offering disease control but limited cure 1 10 16 17.
• Immunotherapy: Immune checkpoint inhibitors (e.g., anti-PD1/PD-L1 drugs) have changed the landscape, providing durable responses in some patients, especially those unfit for chemotherapy or with progression after chemotherapy 10 16 17 19.

Targeted and Emerging Therapies

• Targeted Agents: In patients with actionable mutations (e.g., FGFR3 alterations), targeted therapies offer new options, including FGFR inhibitors and antibody-drug conjugates 10 17 19.
• Clinical Trials: Ongoing research focuses on molecular subtyping to personalize therapy and reduce unnecessary toxicities 7 9 19.

Quality of Life and Follow-Up

Treatment can profoundly affect quality of life, particularly after cystectomy and urinary diversion. Shared decision-making, rehabilitation, and lifelong follow-up are essential components of care 1 10 13.

Conclusion

Bladder cancer is a diverse and complex disease, but progress in understanding its symptoms, types, causes, and treatments is improving outcomes. Here’s a summary of the key points:

• Haematuria is the most important symptom—painless, visible blood in the urine should never be ignored.
• Most bladder cancers are urothelial carcinomas, with non-muscle-invasive and muscle-invasive forms dictating treatment and prognosis.
• Tobacco smoking is the leading cause, but occupational exposures, chronic irritation, and some genetic factors also contribute.
• Treatment is stage-dependent: TURBT and intravesical therapy for NMIBC; radical cystectomy or trimodal therapy for MIBC; and systemic chemotherapy, immunotherapy, and targeted therapy for advanced disease.
• Personalized medicine is emerging, driven by molecular subtyping and biomarker-guided therapies.

Staying informed, seeking timely evaluation, and engaging in shared decision-making with healthcare providers can make a crucial difference in the journey with bladder cancer.