Bacillus Calmette-Guerin: Uses, Dosage, Side Effects and Interactions

Bacillus Calmette-Guerin (BCG) is a unique therapy known for its immunological prowess in treating certain types of bladder cancer. Originally developed as a vaccine for tuberculosis, BCG has found a powerful second life as a cornerstone in uro-oncology, especially for nonmuscle invasive bladder cancer. In this article, we’ll explore the modern clinical uses of BCG, how it’s dosed, its potential side effects, and what is known about its interactions, all grounded in up-to-date research evidence.

Uses of Bacillus Calmette-Guerin

BCG’s role in medicine goes well beyond its origins as a tuberculosis vaccine. Today, it is most famous for its use as an intravesical (bladder) immunotherapy for certain bladder cancers. Let's discover why BCG is so vital in modern urology.

Indication	Patient Group	Purpose/Effectiveness	Sources
Bladder cancer	Nonmuscle invasive (NMIBC)	Prevent recurrence and progression; highly effective as adjuvant therapy	1 3 4 5 7 8 15
Carcinoma in situ (CIS)	Patients with CIS, with or without papillary tumors	High complete response rates, durable effect	3 4 8
Prophylaxis	Patients with prior recurrences	Reduces risk of new tumor formation	1 5 15
Residual tumor therapy	Patients post-surgery with residual disease	Helps eradicate remaining malignant cells	4 5

Table 1: Clinical Uses of Bacillus Calmette-Guerin

BCG for Nonmuscle Invasive Bladder Cancer

• BCG is the gold standard for treating intermediate- and high-risk nonmuscle invasive bladder cancer (NMIBC), especially after transurethral resection of bladder tumors (TURBT).
• Its ability to prevent tumor recurrence and slow disease progression has been consistently demonstrated in randomized clinical trials and long-term studies 3 4 5 7 8 15.

BCG in Carcinoma in Situ (CIS)

• Patients with CIS, sometimes considered the most aggressive form of NMIBC, benefit markedly from BCG instillation.
• Complete response rates as high as 80–94% have been reported, with many patients remaining disease-free for years 3 8.
• Maintenance therapy further reduces the risk of recurrence 3 8.

Prophylactic and Residual Tumor Uses

• BCG is also used to prevent recurrence in patients with a history of multiple bladder tumors and to treat residual carcinoma left after surgery, improving long-term outcomes 1 4 5 15.

Immunological Mechanism

• BCG works by stimulating the immune system within the bladder, leading to local infiltration by immune cells and cytokine release, which destroys cancerous cells 2 16.
• Its activity depends on effective binding to the bladder mucosa, mediated by fibronectin, and triggering both innate and adaptive immune responses 2 16.

Dosage of Bacillus Calmette-Guerin

Navigating BCG dosing can be challenging, as regimens have evolved to balance efficacy with tolerability. Here’s what you need to know about how BCG is administered in clinical practice.

Regimen Type	Typical Dose (mg)	Schedule (weeks/months)	Sources
Standard induction	75–150 mg	Weekly x 6 weeks	3 6 8 9 10
Low-dose induction	13.5–80 mg	Weekly x 6–8 weeks	6 8 9 10
Maintenance therapy	75 mg or lower	Monthly x 12 months or less	3 8 12
Re-treatment	Standard/low-dose	As per initial induction for relapse	4 8 13

Table 2: Common BCG Dosage Regimens

Standard Dosing and Induction Therapy

• The traditional induction course is 6 weekly intravesical instillations using 75–150 mg of BCG 3 6 8.
• Several strains and commercial preparations exist, but most protocols use the Tice or Pasteur strains 3 8.

Low-Dose and Fractionated Regimens

• Research has explored reducing the dose to minimize side effects while maintaining efficacy.
  • Doses as low as 13.5–40 mg (one-sixth to half the standard dose) have shown similar complete response rates in some studies, especially for CIS and intermediate-risk NMIBC 6 8 9 10.
  • For instance, quarter-dose (30 mg) and one-third dose (27 mg) regimens have been found effective in ablative and prophylactic settings 6 9.

Maintenance Therapy

• After the initial induction, maintenance therapy involves periodic instillations (often monthly) for 12 months or more to sustain remission and prevent recurrences 3 8 12.
• Maintenance does not appear to increase toxicity over time and is generally well-tolerated 12.

Re-treatment and Adjustments

• Patients who relapse after initial BCG therapy may receive a repeat induction or maintenance course, sometimes with a higher viability BCG lot if initial response was suboptimal 4 8 13.

Individualization

• Dosing may be adjusted based on patient tolerance, age, comorbidities, and side effect profile.
• The lowest effective dose is often sought, especially in older or frail patients 6 8 10.

Side Effects of Bacillus Calmette-Guerin

Despite its benefits, BCG is not without risks. Most side effects are mild and localized, but systemic complications, though rare, can be serious. Understanding these risks is crucial for both clinicians and patients.

Side Effect	Frequency	Severity	Sources
Bladder irritability (cystitis, dysuria)	Very common (up to 91%)	Mild–moderate	11 13 14 15
Hematuria (blood in urine)	Common (39%)	Usually mild	11 13 14 15
Fever, malaise	Common (22–42%)	Mild–rarely severe	11 13 14 15
Granulomatous prostatitis/cystitis	Uncommon (~1–16%)	Usually mild	11 13 14 15
Systemic infection (sepsis, hepatitis, pneumonitis)	Rare (<1%)	Severe, life-threatening	11 13 14
Bladder contracture, ureteral obstruction	Very rare (<1%)	Severe	14

Table 3: Common and Serious Side Effects of BCG Therapy

Local Side Effects

• The majority of patients experience some form of bladder irritation:
  • Dysuria (painful urination), frequency, urgency, and mild hematuria are the norm 11 13 14 15.
  • These symptoms typically arise during or shortly after instillation and are usually self-limited 13.
  • Granulomatous cystitis and prostatitis can occur but are generally mild 13 14.

Systemic Reactions

• Systemic symptoms such as fever, malaise, and flu-like symptoms affect a minority of patients and are usually mild 11 13 14 15.
• Severe systemic complications (e.g., BCG sepsis, hepatitis, pneumonitis, or disseminated infection) are rare but potentially life-threatening 11 13 14.
  • Risk factors include traumatic catheterization and concurrent urinary tract infection, which may increase systemic absorption of BCG 11.

Rare Complications

• Extremely rare side effects include arthritis, skin abscesses, epididymo-orchitis, bladder contracture, and cytopenia 14.
• Fatal reactions have been reported but are exceedingly uncommon (well under 1%) 11 13 14.

Dose and Side Effect Correlation

• Lower-dose regimens are associated with fewer local and systemic side effects and improved patient quality of life, without substantial loss of efficacy in selected populations 8 9 10.
• Most severe reactions occur within the first 6 months of therapy; long-term maintenance does not increase toxicity 12.

Management of Side Effects

• Most side effects are managed symptomatically.
  • Delaying or withholding BCG, using antituberculous drugs (e.g., isoniazid), and anti-inflammatory medications can help 3 11 14.
  • Prophylactic isoniazid may reduce severe irritative and systemic complications 14.
  • Life-threatening systemic reactions require rapid initiation of antituberculous therapy and sometimes cycloserine 14.

Interactions of Bacillus Calmette-Guerin

While BCG is not a conventional drug in terms of metabolic interactions, its immunological nature means certain factors and concomitant medications can alter its effects—or its side effects.

Interaction Type	Effect on BCG	Clinical Relevance	Sources
Immunosuppressants	Reduced efficacy, increased risk of infection	Avoid concurrent use	13 14
Antituberculous drugs (isoniazid, etc.)	May reduce BCG viability if given systemically	Used to manage severe side effects	11 14
Antibiotics/urinary antiseptics	May inactivate BCG in the bladder	Avoid during BCG therapy	4
Traumatic catheterization or cystitis	Increased risk of systemic absorption and toxicity	Take precautions; delay therapy if present	11

Table 4: Notable Interactions Impacting BCG Therapy

Immunosuppressive Medications

• BCG should not be used in patients receiving systemic immunosuppressive therapy (e.g., corticosteroids, chemotherapy, or biologics) due to the risks of disseminated infection and reduced efficacy 13 14.

Antituberculous Drugs and Antibiotics

• Agents such as isoniazid and rifampin, when used concurrently, can lower BCG viability and thus reduce therapeutic efficacy if administered systemically 4 11.
• However, these drugs play a critical role in managing severe or systemic BCG-induced infections 11 14.
• Use of urinary antibiotics or antiseptics during BCG instillation can inactivate BCG and should be avoided unless absolutely necessary 4.

Urogenital Tract Injuries and Infections

• Traumatic catheterization or concurrent urinary tract infection can dramatically increase the risk of systemic BCG complications and should be addressed before therapy 11.
• Elective postponement of BCG is recommended in these settings 11.

Other Considerations

• No significant metabolic drug–drug interactions are documented, as BCG acts via immune mechanisms rather than through traditional pharmacokinetics.
• Interactions with vaccines, especially other live vaccines, should be approached cautiously.

Conclusion

Bacillus Calmette-Guerin remains a mainstay in the management of nonmuscle invasive bladder cancer, offering proven benefits in recurrence and progression prevention. Its use, however, must be carefully balanced with consideration for dosing, side effects, and potential interactions.

Key Points Covered:

• Clinical Uses: BCG is highly effective for NMIBC, CIS, and as prophylaxis against tumor recurrence.
• Dosage: Induction (6 weekly doses) and maintenance regimens are standard; lower doses may reduce toxicity with similar efficacy for many patients.
• Side Effects: Most are mild and localized. Serious, systemic complications are rare but require prompt recognition and management.
• Interactions: Avoid in immunosuppressed patients or during active urinary infections; antibiotic/antituberculous agents can impact efficacy or be needed for side effect management.

For patients and providers, understanding the nuances of BCG therapy is key to maximizing outcomes and minimizing risks. This evidence-based overview helps clarify the essentials, supporting informed, safe, and effective use of this time-tested immunotherapy.