Urinary bladder cancer is a malignant neoplasm arising from the urinary bladder epithelium or supporting connective tissues. It is one of the most common urological cancers worldwide and may present as non-muscle-invasive disease, muscle-invasive disease, or metastatic disease.

The most common histological type is urothelial (transitional cell) carcinoma, which accounts for the majority of cases. Other histological subtypes include:

• Squamous cell carcinoma

• Adenocarcinoma

• Sarcoma

• Secondary metastatic deposits

In regions where schistosomiasis is endemic, squamous cell carcinoma occurs more frequently due to chronic inflammation and irritation of the bladder mucosa.

Management depends largely on the depth of tumour invasion, histological subtype, tumour grade, and presence of regional or distant metastases.

Epidemiology

Bladder cancer is among the most common malignancies of the urinary tract.

Epidemiological characteristics include:

• More common in males than females

• Incidence increases with age

• Urothelial carcinoma is the predominant histological subtype worldwide

• Squamous cell carcinoma is relatively more common in areas endemic for schistosomiasis

• Tobacco smoking is the leading preventable risk factor

Risk factors

Chronic bladder irritation

Including:

• Schistosomiasis

• Long-term catheterization

• Chronic urinary tract infections

• Previous pelvic irradiation

Tobacco smoking

Smoking is the most important modifiable risk factor and significantly increases the risk of bladder cancer.

Occupational chemical exposure

Including exposure to:

• Aromatic amines

• Aniline dyes

• Industrial chemicals

• Rubber manufacturing products

Medications and chemical agents

Including prolonged exposure to:

• Certain analgesics

• Chemotherapeutic agents such as cyclophosphamide

Genetic predisposition

A family history of bladder cancer may increase susceptibility.

Increasing age

Risk increases significantly after the fifth decade of life.

Pathophysiology

Bladder cancer develops through progressive genetic and molecular alterations within the urothelial lining.

The disease process generally follows:

1. Chronic mucosal irritation or carcinogen exposure

2. Cellular dysplasia

3. Carcinoma in situ (CIS)

4. Invasive carcinoma

5. Regional lymphatic spread

6. Distant metastasis

Tumours may be classified as:

Non-muscle-invasive bladder cancer (NMIBC)

Includes:

• Ta tumours

• T1 tumours

• Carcinoma in situ (CIS)

Muscle-invasive bladder cancer (MIBC)

Tumours invading the detrusor muscle or beyond.

Common metastatic sites include:

• Lymph nodes

• Liver

• Lung

• Bone

Clinical presentation

Clinical manifestations depend on:

• Tumour size

• Tumour location

• Degree of invasion

• Presence of metastases

Painless haematuria is the most common presenting symptom.

Symptoms

Urinary symptoms

• Gross haematuria

• Microscopic haematuria

• Dysuria

• Urinary frequency

• Urgency

• Nocturia

• Lower urinary tract symptoms (LUTS)

Pain symptoms

• Suprapubic pain

• Pelvic pain

• Low back pain

• Flank pain

Symptoms of advanced disease

• Weight loss

• Fatigue

• Bone pain

• Lower limb oedema

• Constitutional symptoms

Clinical signs

General findings

• Pallor secondary to chronic blood loss

• Weight loss

• Cachexia

• Reduced performance status

Abdominal findings

• Suprapubic tenderness

• Palpable pelvic mass in advanced disease

Findings on bimanual examination

May reveal:

• Bladder fixation

• Pelvic extension

• Adjacent organ involvement

Signs of metastatic disease

• Bone tenderness

• Pathological fractures

• Hepatomegaly

• Lymphadenopathy

Differential diagnosis

• Urinary tract infection

• Urolithiasis

• Benign prostatic hyperplasia

• Prostatitis

• Renal cell carcinoma

• Urothelial carcinoma of the upper urinary tract

• Schistosomiasis

• Interstitial cystitis

• Radiation cystitis

• Tuberculosis of the urinary tract

Diagnostic criteria

Bladder cancer should be suspected in patients presenting with:

• Painless haematuria

• Persistent microscopic haematuria

• Dysuria without evidence of infection

• Persistent lower urinary tract symptoms

• Unexplained pelvic or low back pain

Diagnosis is confirmed by:

• Cystoscopic visualization of the lesion

• Histopathological examination of biopsy or TURBT specimens

Investigations

Laboratory investigations

Full blood count (FBC)

Used to assess:

• Anaemia

• Baseline treatment status

Renal function tests (RFTs)

Including:

• Urea

• Creatinine

Liver function tests (LFTs)

Assess hepatic function and possible metastatic involvement.

Alkaline phosphatase (ALP)

May be elevated in bone or liver metastases.

Urine investigations

Urinalysis

Used to detect:

• Haematuria

• Infection

Urine culture and sensitivity

Helps exclude urinary tract infection.

Urine cytology

Useful for detection of:

• High-grade urothelial carcinoma

• Carcinoma in situ

Imaging investigations

Chest X-ray (CXR)

Used to assess pulmonary metastases.

CT chest

Provides detailed assessment of thoracic disease.

Ultrasound of abdomen and pelvis

Useful for:

• Detection of bladder masses

• Assessment of hydronephrosis

• Evaluation of pelvic organs

CT scan of abdomen and pelvis

Used for:

• Local staging

• Evaluation of lymph node involvement

• Detection of metastatic disease

PET/CT

Useful in selected patients with advanced disease.

Bone scan

Indicated when:

• Bone pain is present

• Elevated alkaline phosphatase is detected

• Metastatic disease is suspected

Endoscopic investigations

Cystoscopy with bladder mapping and biopsy

Essential for:

• Direct tumour visualization

• Determining tumour extent

• Histological diagnosis

Examination under anaesthesia (EUA)

Assesses:

• Local extension

• Tumour fixation

Bimanual examination

Evaluates:

• Pelvic involvement

• Mobility of the bladder

Surgical diagnostic procedures

Transurethral resection of bladder tumour (TURBT)

Used for:

• Histological diagnosis

• Local staging

• Initial treatment

Random biopsies of normal-appearing mucosa may be performed to exclude carcinoma in situ.

When the trigone is involved:

• Biopsy of the prostatic urethra should be considered.

Staging

Urinary bladder cancer is staged using the TNM staging system.

T – Primary tumour

Determined by:

• Depth of bladder wall invasion

• Adjacent organ involvement

N – Regional lymph nodes

Determined by:

• Pelvic lymph node involvement

M – Distant metastasis

Determined by spread to:

• Liver

• Lung

• Bone

• Other distant organs

Management

Management depends on:

• Depth of invasion

• Histological subtype

• TNM stage

• Patient performance status

• Presence of metastases

Management pathway:

1. Confirm diagnosis by TURBT and histology

2. Stage disease

3. Determine muscle invasion status

4. Assess surgical fitness

5. Initiate definitive treatment

6. Provide long-term surveillance

Non-pharmacological treatment

Surgery

Bladder-preserving surgery

Transurethral resection of bladder tumour (TURBT)

Indicated for:

• Non-muscle-invasive bladder cancer

• Diagnostic and therapeutic purposes

Radical cystectomy

Indicated for:

• Muscle-invasive disease

• High-risk recurrent disease

• Selected locally advanced tumours

Usually combined with:

• Pelvic lymph node dissection

• Urinary diversion procedures

Urinary diversion

May include:

• Ileal conduit

• Continent urinary diversion

• Orthotopic neobladder

Follow-up surveillance

Includes:

• Periodic cystoscopy

• Urine cytology

• Imaging studies

• Assessment for recurrence

Pharmacological treatment

Neoadjuvant chemotherapy

May be administered before radical surgery to improve outcomes in muscle-invasive disease.

Adjuvant chemotherapy

May be administered after surgery in selected high-risk patients.

Concurrent chemoradiotherapy

May be used as a bladder-preservation strategy in selected patients.

Locally advanced or metastatic disease

Gemcitabine and cisplatin regimen

Gemcitabine – 1000 mg/m² – intravenous infusion over 30 minutes – days 1, 8, and 15ANDCisplatin – 70 mg/m² – intravenous infusion – day 2

Frequency:

• Every 28 days

Duration:

• 6 cycles

MVAC regimen

Methotrexate – 30 mg/m² – intravenous injection over 5 minutes – days 1, 15, and 22ANDVinblastine – 3 mg/m² – intravenous infusion over 10 minutes – days 2, 15, and 22ANDDoxorubicin – 30 mg/m² – intravenous infusion over 15 minutes – day 2ANDCisplatin – 70 mg/m² – intravenous infusion over 30 minutes – day 2

Administer according to institutional chemotherapy protocols.

Management according to disease stage

Non-muscle-invasive bladder cancer

Management includes:

• TURBT

• Histological assessment

• Surveillance cystoscopy

Muscle-invasive bladder cancer

Management options include:

• Radical cystectomy with urinary diversion

• Neoadjuvant chemotherapy

• Adjuvant chemotherapy

• Bladder-preserving chemoradiotherapy in selected patients

Locally advanced disease

Management may include:

• Radical surgery

• Chemotherapy

• Radiotherapy

• Combined modality treatment

Metastatic disease

Management includes:

• Systemic chemotherapy

• Palliative radiotherapy

• Symptom-directed supportive care

Radiotherapy

Radical radiotherapy

May be used:

• Following bladder-preserving surgery

• As definitive treatment for selected small lesions

Recommended dose:

• Up to 66 Gy in 33 fractions

Often administered concurrently with cisplatin.

Palliative radiotherapy

Indications include:

• Haematuria

• Pelvic pain

• Locally advanced disease

• Metastatic disease

Recommended regimens:

• 30 Gy in 10 fractions

OR

• 20 Gy in 5 fractions

Referral

All patients with suspected or confirmed bladder cancer should be referred to specialized urology and oncology centres.

Urgent referral indications

• Gross haematuria

• Recurrent unexplained haematuria

• Urinary obstruction

• Suspected muscle-invasive disease

• Suspected metastatic disease

• Severe bleeding requiring intervention

Complications

Disease-related complications

• Persistent haematuria

• Anaemia

• Urinary obstruction

• Hydronephrosis

• Renal impairment

• Local pelvic invasion

• Metastatic disease

Treatment-related complications

Surgery

• Urinary diversion complications

• Infection

• Bleeding

• Sexual dysfunction

Chemotherapy

• Myelosuppression

• Nephrotoxicity

• Peripheral neuropathy

• Nausea and vomiting

Radiotherapy

• Radiation cystitis

• Radiation proctitis

• Bladder fibrosis

• Urinary frequency

Prognosis

Prognosis depends on:

• Tumour stage

• Histological subtype

• Grade

• Presence of muscle invasion

• Lymph node involvement

• Distant metastases

Non-muscle-invasive disease generally has a favourable prognosis with appropriate treatment and surveillance. Muscle-invasive and metastatic disease are associated with poorer outcomes.

Prevention

Primary prevention

• Smoking cessation

• Reduction of occupational chemical exposure

• Prevention and treatment of schistosomiasis

• Avoidance of chronic bladder irritation

Secondary prevention

• Early evaluation of haematuria

• Prompt investigation of persistent urinary symptoms

• Surveillance of high-risk individuals

Tertiary prevention

• Regular follow-up after treatment

• Early detection of recurrence

• Prevention of treatment-related complications