What are the potential complications of Bacillus Calmette-Guérin (BCG) therapy in patients with a history of bladder cancer?

BCG Therapy Complications in Bladder Cancer

BCG therapy for bladder cancer causes local and systemic complications in approximately 70% of patients, with the most common being chemical cystitis (35%), flu-like symptoms (15%), and serious adverse events requiring treatment discontinuation in 8% of cases. 1

Local Complications

Chemical Cystitis and Lower Urinary Tract Symptoms

• Dysuria, frequency, and urgency occur in 60% of patients and represent the most frequent local side effects 2
• Chemical cystitis affects 35% of patients and is most severe in those with decreased bladder compliance before treatment 3
• Hematuria, bladder pain, and prostatitis are common across all intravesical treatments 4
• Symptom management with single-dose, short-term quinolones and/or anticholinergics reduces adverse events 2

Granulomatous Complications

• Bladder granulomas develop in approximately 30% of patients within the first 6 months after treatment 3
• These changes are temporary and do not correlate with long-term voiding symptoms 3
• Extravesical granulomas occur in 37% of patients and can cause urinary tract obstruction in 9% 3
• Late bladder contracture is rare when properly managed 3

Granulomatous Cystitis Management

• Immediately suspend BCG instillations when granulomatous cystitis develops 5, 6
• Initiate anti-tuberculosis therapy with isoniazid and rifampicin for 3 months, plus quinolones and corticosteroids 6
• Consider intravesical quinolone and anti-inflammatory instillations daily for 5 days if symptoms persist 6

Systemic Complications

Flu-like Symptoms

• Systemic symptoms resembling influenza occur in 31% of patients and typically last 48-72 hours 1, 2
• BCG induces a non-specific immunostimulatory response with pro-inflammatory cytokine secretion 2, 5
• The immune response activates neutrophils, monocytes, macrophages, T cells, and NK cells 2, 7
• Severe systemic symptoms occur in approximately 6% of patients 3

Serious Systemic Complications

• Potentially serious complications occur in 6% of patients, including sepsis and death 3, 2
• Hypersensitivity pneumonitis can develop from granulomatous inflammation in the lungs 5
• Patients with persistent flu-like symptoms beyond 72 hours require immediate evaluation for systemic BCG infection 5

Hypersensitivity Pneumonitis

• Immediately suspend BCG instillations when hypersensitivity pneumonitis is suspected 5
• Patients with prior BCG-induced hypersensitivity pneumonitis should never receive further BCG therapy 5
• Alternative intravesical agents must be considered for ongoing bladder cancer management 5

Risk Factors for Complications

Patient-Related Factors

• Decreased bladder capacity under anesthesia predicts severe cystitis 3
• Immunosuppression is a relative contraindication to BCG use 3
• BCG has cumulative effects, so increased toxicity occurs during long-term administration 3

Procedure-Related Factors

• Traumatic catheterization or instillation within 2 weeks of TURBT increases systemic absorption risk 5
• Pretreatment skin reactivity does not correlate with toxicity 3

Treatment Discontinuation

Frequency and Timing

• 8% of patients stop treatment due to side effects 1
• Among patients receiving 3-year BCG maintenance, 5.4% stop during the first year and 3.2% stop in years 2-3 1
• Side effects requiring treatment cessation occur most frequently in the first year 1

Management Strategies

• Reduce BCG dose (used in 17% of patients with toxicity) 3
• Temporarily interrupt treatment (5% of patients) 3
• Permanent cessation (4% of patients) 3
• One-third dose BCG has similar side effect profiles to full dose 1

BCG Intolerance Definition

• BCG-intolerant disease is defined as persistent disease due to inability to receive adequate BCG because of toxicity 2
• These patients require alternative management strategies including radical cystectomy or alternative intravesical agents 2

Critical Safety Considerations

Contraindications in Other Conditions

• BCG should never be offered for interstitial cystitis/bladder pain syndrome outside investigational settings due to lack of efficacy and serious adverse events including sepsis and death 2

Monitoring Requirements

• Monitor for persistent symptoms beyond 48-72 hours after each instillation 5
• Regular cystoscopic surveillance at 3-6 month intervals to detect complications early 6
• Watch for signs of upper tract involvement requiring imaging 6