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Intravesical BCG Instillation: Adverse Effects, Contraindications and Dosage

Mechanism of Action of BCG

Intravesical instillation of bacillus Calmette-Guérin (BCG) into the urinary bladder induces a localized granulomatous cystitis. This process activates neutrophils, lymphocytes, and additional effector cells of both the innate and adaptive immune system. The resulting inflammatory response mediates cytotoxic effects against urothelial tumor cells and promotes the development of antitumor immunity (Bohle and Brandau, 2003).

Urological Indications

BCG is indicated for intravesical immunotherapy of non–muscle-invasive bladder cancer (NMIBC) with intermediate- or high-risk of recurrence and/or progression, including carcinoma in situ; see the tables on recurrence risk and progression risk.

Adverse Effects of Bacillus Calmette-Guérin (BCG)

Adverse events associated with intravesical BCG are relatively common.

Frequency >10%:

Pollakiuria, dysuria, and hematuria; asymptomatic granulomatous prostatitis; influenza-like symptoms; and fever < 38 °C occur commonly (incidence > 10%).

Frequency 1–10%:

Fever > 38 °C, persistent fever should be evaluated for systemic BCG infection.

Frequency <1%:

Allergic skin reactions, orchitis, miliary pneumonia, abscess-forming infections after systemic dissemination, BCG-related sepsis, ureteral stricture with upper urinary tract obstruction, and reduced bladder capacity.

Contraindications of BCG

Contraindications to intravesical BCG include clinically relevant immunosuppression (e.g., due to systemic glucocorticoid therapy), pregnancy, active tuberculosis, bladder perforation, symptomatic urinary tract infection, macroscopic hematuria, traumatic catheterization, and a transurethral resection of bladder tumor (TURBT) within the previous 21 days.

Dosage of BCG

One vial contains, depending on the commercial preparation, approximately 2×10⁸ bis 3×10⁹ viable BCG bacteria. After suspension with 50 mL of 0.9% sodium chloride, BCG is instilled intravesically via a single-use catheter once weekly for six weeks. To achieve a dwell time of 1–2 hours, the patient should limit fluid intake to small amounts for several hours before instillation.

Assess the response to treatment primarily with cystoscopy and urine cytology after three months. If cystoscopy reveals abnormalities or cytology is positive, perform re-TURBT or quadrant bladder biopsies. In patients with extensive tumor involvement, consider re-TURBT of the scar region. In patients who respond to intravesical immunotherapy, maintenance BCG is advisable: three weekly instillations at months 3, 6, 12, 18, 24, 30, and 36 (SWOG maintenance schedule). Depending on adverse events and the individual risk profile, maintenance therapy is usually continued for 1–3 years.

Dose Adjustment and Treatment Interruptions

Intravesical administration of BCG frequently causes local and occasionally systemic adverse events that may necessitate treatment discontinuation or temporary interruption.

Dysuria >2 Days:

If dysuria persists for more than two days, interrupt BCG therapy, obtain a urine culture, and initiate empirical antibiotic therapy if clinically indicated. Resume BCG instillations only after complete resolution of symptoms.

Dysuria >10 Days, Symptomatic Prostatitis or Orchitis:

If dysuria lasts longer than ten days or the patient develops symptomatic prostatitis or orchitis, discontinue BCG therapy and initiate antituberculous treatment (e.g., isoniazid, rifampin, and ethambutol) for 3–6 months, depending on severity and clinical course.

Fever <38.5 °C for <2 Days:

Provide symptomatic treatment with acetaminophen (paracetamol) and monitor the clinical course.

Skin Rash, Arthralgia or Arthritis:

Interrupt BCG therapy and treat with nonsteroidal anti-inflammatory drugs (NSAIDs). Consider a short course of systemic corticosteroids. If symptoms do not improve, discontinue BCG therapy permanently and initiate antituberculous treatment.

Severe Systemic Adverse Effects or Disseminated Infection:

In the case of severe systemic adverse events or clinical evidence of disseminated BCG infection, discontinue BCG therapy and promptly initiate antituberculous treatment for six months in close collaboration with an infectious disease specialist.

References

Bohle, A. & Brandau, S. Immune mechanisms in bacillus Calmette-Guerin immunotherapy for superficial bladder cancer
J Urol, 2003, 170, 964-9.

Review Literature: EAU guidelines superficial bladder cancer. EAU guidelines of muscle-invasive and metastatic bladder cancer. German S3 guidelines bladder carcinoma Harnblasenkarzinom.

  Deutsche Version: Nebenwirkungen und Kontraindikationen der intravesikalen Therapie mit BCG

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