BCG Intravesical Therapy

Intravesical Bacillus Calmette-Guérin (BCG) therapy uses a live attenuated mycobacterial strain instilled directly into the bladder as immunotherapy for non-muscle-invasive bladder cancer (NMIBC). It is one of the most effective treatments for high-grade NMIBC and carcinoma in situ (CIS).

Mechanism of Action

After intravesical instillation, BCG comes into direct contact with the bladder urothelium and any residual tumor cells. It triggers a cascade of local and adaptive immune responses:

• Activates dendritic cells and macrophages.
• Recruits T cells and other lymphocytes to the bladder wall.
• Enhances both cellular and humoral immunity.
• Produces direct cytotoxic effects on tumor cells and induces apoptosis.
• Promotes long-term immune surveillance against tumor recurrence.

Note: this is intravesical immunotherapy, not the BCG vaccine for tuberculosis prevention — although the underlying organism is the same, the route, dose, and clinical purpose differ entirely.

• Reduces tumor recurrence by approximately 40–50% compared with intravesical chemotherapy.
• Reduces progression to muscle-invasive disease by approximately 25–40%.
• Complete response rates of 70–90% in patients with carcinoma in situ.
• Considered the gold standard for high-grade NMIBC and CIS, superior to intravesical mitomycin C and doxorubicin.

Non-muscle-invasive bladder cancer (NMIBC), particularly:

• High-grade Ta, T1 tumors.
• Carcinoma in situ (CIS) — most responsive.
• After transurethral resection of bladder tumor (TURBT).
• Both as induction therapy and as maintenance therapy.

Treatment goals: prevent tumor recurrence, prevent progression to muscle-invasive disease, preserve bladder function, and reduce the need for radical cystectomy.

• Hypersensitivity to the active substance or any excipient.
• Immunosuppressed patients — congenital or acquired immune deficiency, HIV-positive, leukaemia, lymphoma, or those receiving cytostatic drugs, radiotherapy, or systemic corticosteroids.
• Active tuberculosis or current treatment with anti-TB drugs.
• Prior bladder radiotherapy.
• Pregnancy and breastfeeding.
• Instillation within 2–3 weeks of TUR, biopsy, or traumatic catheterisation.
• Bladder perforation.
• Acute urinary tract infection.

Critical Route Warning

BCG-Medac must not be administered subcutaneously, intradermally, intramuscularly, or intravenously, and must not be used for vaccination. The product is intended exclusively for intravesical instillation.

Local adverse reactions occur in approximately 90% of patients; the cystitis and inflammatory reaction are considered essential to the anti-tumour effect.

Very Common (≥1/10)

Cystitis, bladder granuloma, asymptomatic granulomatous prostatitis; transient systemic BCG reaction (fever <38.5°C, flu-like symptoms, malaise); urinary frequency with discomfort; nausea; fatigue.

Common (≥1/100 to <1/10)

Diarrhoea, abdominal pain, myalgia, fever >38.5°C, urinary incontinence.

Uncommon (≥1/1,000 to <1/100)

Urinary tract infection, orchitis, epididymitis, symptomatic granulomatous prostatitis, hepatitis, severe systemic BCG reaction, BCG sepsis, miliary pneumonitis, skin abscess, Reiter’s syndrome (reactive arthritis, conjunctivitis, urethritis — particularly in HLA-B27 positive patients), cytopenia, anaemia, hypotension, pulmonary granuloma, skin rash, arthritis, macroscopic haematuria, bladder retention.

Rare (≥1/10,000 to <1/1,000)

Vascular infection (e.g. infected aneurysm), renal abscess, cervical lymphadenitis.

Very Rare (<1/10,000)

BCG infection of implants/grafts, regional lymph node infection, osteomyelitis, peritonitis, chorioretinitis, vasculitis.

Severe Systemic BCG Infection

Severe systemic BCG infections/reactions have been reported in fewer than 5% of patients. Traumatic instillation may precipitate BCG-septicaemic events with possible septic shock. Flare-up of latent BCG infection may occur years after treatment, presenting with fever and weight loss of unknown origin — patients should remain alert to this possibility long-term.

Induction Therapy

• One vial reconstituted as indicated, instilled intravesically once weekly for 6 weeks.
• Begin approximately 2–3 weeks after transurethral resection (TUR) or bladder biopsy, provided no gross haematuria or major bladder irritability is present.
• Suspension retained in the bladder for 2 hours; patient repositions periodically (supine, prone, left and right lateral) to maximise mucosal contact.
• Fluid intake should be restricted from 4 hours before until 2 hours after instillation.

Maintenance Therapy

Per the BCG-Medac SmPC schedule:

• 3 weekly instillations at months 3, 6, and 12 after initiation.
• Continued at 6-monthly intervals (3-instillation cycles) for up to 3 years total.

Pre-Treatment Requirements

• TURBT must be performed before BCG therapy to remove gross tumor.
• Wait 2–3 weeks after TURBT for adequate bladder healing.
• Treat any active urinary tract infection prior to BCG.

Administration Technique

• Aseptic catheterization.
• Instill BCG suspension into the bladder.
• Clamp catheter, then remove.
• Patient retains BCG suspension for ~2 hours, repositioning regularly.
• After voiding, BCG-containing urine should be inactivated with bleach or other disinfectant.

Patient Instructions

• Maintain hydration to dilute urine.
• Avoid sexual contact for 48 hours after instillation (theoretical transmission risk).
• Pour bleach into the toilet for 15 minutes after voiding before flushing during the first 6 hours after each dose.

BCG is sensitive to anti-tuberculosis medicinal products including ethambutol, streptomycin, p-aminosalicylic acid, isoniazid, and rifampicin, as well as antibiotics such as fluoroquinolones, doxycycline, and gentamicin. Resistance is documented against pyrazinamide and cycloserine. Antibiotic use during therapy will inactivate the BCG and necessitates postponing instillation until the antibiotic course is complete.

Systemic immunosuppressants may reduce BCG efficacy and are contraindicated. Live vaccines should be avoided during BCG therapy. Intravesical chemotherapy may be used before BCG in selected protocols.

Patient Education (Critical)

• Expect dysuria, frequency, and urgency for 24–48 hours (normal, not infection).
• Inactivate BCG-containing urine with bleach for the first 6 hours after each dose.
• Maintain hydration.
• Report fever >38.5°C, severe symptoms, or persistent symptoms.
• Avoid sexual contact for 48 hours.

Fever Management

Low-grade fever occurs in 10–15% of patients after BCG. Usually self-limited. NSAIDs may be used for comfort. Seek medical attention for fever >38.5°C or persistent fever.

Severe BCG Toxicity (“BCG-itis”)

• Symptoms: high fever (>39°C), severe systemic symptoms, severe persistent dysuria.
• Treatment: anti-tuberculosis therapy with isoniazid 5 mg/kg daily, rifampin 10 mg/kg daily, and ethambutol 15 mg/kg daily, continued for 3–6 months.
• Stop intravesical BCG; do not rechallenge.
• Hospitalize if sepsis is present.

Pregnancy, Lactation, and Fertility

Pregnancy data are absent or limited; BCG-Medac is not recommended during pregnancy and is contraindicated during breast-feeding. Intravesical BCG therapy adversely affects spermatogenesis and may cause oligospermia or azoospermia; men of reproductive age should be counselled to seek advice about sperm preservation before starting therapy. Sexual contact should be avoided or protected for one week after each instillation.

Immunocompromised Patients

Avoid in patients with severe immunosuppression. Specifically contraindicated in:

• HIV with CD4 <200.
• Patients on biologic agents or TNF inhibitors.
• Other severely immunosuppressed states (risk of disseminated BCG infection).

Monitoring

• Urinalysis or urine culture before each instillation.
• Fever and symptom log.
• Long-term cystoscopic surveillance per protocol.

Treatment Failure

Approximately 20–30% of patients are non-responders. Options include repeat BCG induction, alternative maintenance protocols, intravesical chemotherapy, or radical cystectomy.

Store unopened vials at 2–8°C, protected from light. The freeze-dried preparation must be reconstituted just before use using aseptic technique. After reconstitution, use immediately and discard any unused portion.

2 years unopened when stored at 2–8°C, in the original package and protected from light. Do not freeze. Once reconstituted, use immediately. Do not use after the expiry date.

Prescription required. Administered by trained urology healthcare professionals in clinical settings with proper patient education and supportive care resources.