What is the recommended treatment protocol for BCG (Bacillus Calmette-Guérin) therapy in patients with non-muscle-invasive bladder cancer?

BCG Treatment Protocol for Non-Muscle Invasive Bladder Cancer

For patients with intermediate or high-risk non-muscle invasive bladder cancer, BCG induction therapy followed by maintenance therapy is the recommended treatment protocol to reduce recurrence and progression rates.

Patient Risk Stratification

The appropriate BCG treatment protocol depends on the risk category:

Low-Risk NMIBC

• Do not use BCG therapy for low-risk disease 1
• Instead, use a single immediate post-TURBT chemotherapy instillation 1

Intermediate-Risk NMIBC

• Six-week induction course of BCG 1
• Consider maintenance BCG for one year, as tolerated 1
• Alternative: Intravesical chemotherapy may be considered 1

High-Risk NMIBC

• Six-week induction course of BCG 1
• Maintenance BCG for three years, as tolerated 1
• This is the gold standard for high-risk patients 2

Standard BCG Treatment Protocol

Preparation and Administration

• Allow 7-14 days after bladder biopsy before starting BCG 3
• Patient should not drink fluids for 4 hours before treatment 3
• Empty bladder prior to BCG administration 3
• BCG is reconstituted in 50 mL preservative-free saline 3
• Instill via catheter using gravity flow 3
• Retain in bladder for 2 hours if possible 3
• During retention, patient should change position every 15 minutes (left side, right side, back, abdomen) to maximize bladder surface exposure 3

Treatment Schedule

1. Induction Phase:

   • One intravesical instillation per week for 6 weeks 3

2. Maintenance Phase:

   • For intermediate-risk: Consider maintenance for one year 1
   • For high-risk: Continue maintenance for three years 1
   • Standard maintenance schedule: Monthly instillations for at least 6-12 months 3

Management of BCG Side Effects

Local Side Effects

• Cystitis symptoms: For mild symptoms, use bladder irritation relief drugs, anticholinergics, and NSAIDs. If symptoms persist >48 hours, postpone instillation, perform urine culture, and start empirical antibiotics 1
• Hematuria: Perform urine culture to exclude hemorrhagic cystitis. Resume instillation when urine is clear. For macroscopic hematuria, consider catheter placement and continuous bladder irrigation 1
• Granulomatous prostatitis: If symptomatic, perform urine culture, suspend instillation, and give isoniazid and rifampicin for three months 1

Systemic Side Effects

• Monitor for fever >38.5°C, severe pain, malaise, fatigue 4
• If severe systemic symptoms occur, discontinue BCG and consider antituberculous therapy

BCG Failure Management

If BCG therapy fails:

• BCG-refractory disease: Consider radical cystectomy as the standard recommendation 1, 5
• For patients unsuitable for cystectomy, alternative options include:
  • Second course of BCG (response rate ~50%) 1
  • Alternative intravesical agents (gemcitabine, docetaxel) 6, 7
  • Device-assisted therapies such as thermochemotherapy 7

Special Considerations

• BCG should not be interchanged between different BCG products 3
• For patients with asymptomatic bacteriuria, BCG can still be administered 1
• In immunocompromised patients, use BCG with caution 1
• Consider combination therapy with BCG and chemotherapy for select high-risk patients 1

Monitoring Response

• Regular cystoscopy and cytology every 3 months during the first 2 years 1
• For patients with CIS, mandatory cytology with each cystoscopy 1
• Appropriate upper-tract evaluation at the end of study period 1

BCG therapy has been shown to improve recurrence-free survival, overall survival, and disease-specific survival compared to intravesical chemotherapy alone 1, making it the treatment of choice for high-risk non-muscle invasive bladder cancer.