What is the BCG (Bacillus Calmette-Guérin) induction and maintenance schedule for bladder cancer?

BCG Induction and Maintenance Schedule for Bladder Cancer

Standard Induction Schedule

BCG induction consists of weekly intravesical instillations for 6 consecutive weeks, initiated at least 2 weeks after transurethral resection or bladder biopsy. 1

• Each instillation uses one full vial of BCG (TICE® 50 mg or Theracys® 81 mg, containing approximately 5 × 10⁸ CFU) suspended in 50 mL preservative-free saline 1, 2
• The suspension is retained in the bladder for 2 hours before voiding 2
• Never administer BCG within 24 hours of bladder tumor resection—this can be dangerous due to systemic absorption risk 1
• Allow 4-6 weeks rest period after completing induction before performing re-evaluation cystoscopy 1, 3

Maintenance Schedule: The SWOG Protocol

For patients achieving complete response after induction, maintenance BCG using the SWOG schedule consists of 3 weekly instillations at months 3,6,12,18,24,30, and 36 after the start of induction. 1

This translates to:

• 3 weekly instillations at month 3 (approximately 12 weeks after starting induction) 1
• 3 weekly instillations at month 6 1
• 3 weekly instillations at month 12 1
• 3 weekly instillations at months 18,24,30, and 36 (for high-risk patients only) 1

Duration Based on Risk Stratification

High-Risk NMIBC (High-grade Ta, T1, or CIS)

All high-risk patients should receive full 3-year maintenance therapy (total of 7 maintenance cycles at the timepoints listed above). 1

• Three-year maintenance significantly reduces recurrence compared to 1-year maintenance (HR 1.61,95% CI 1.13-2.30, P = 0.01) 1
• This is the only schedule proven to reduce disease progression and mortality in randomized trials 1
• Level A evidence supports this recommendation 1

Intermediate-Risk NMIBC

Intermediate-risk patients should receive maintenance therapy for at least 1 year (maintenance cycles at months 3,6, and 12 only). 1

• The EORTC 98013 trial suggests 1 year of SWOG maintenance is sufficient for intermediate-risk patients 1
• However, recurrence directly correlates with duration of maintenance, with longer treatment resulting in fewer recurrences 1
• Twelve months of BCG (induction plus maintenance at 3,6, and 12 months) is recommended as standard 1

Critical Timing and Safety Considerations

BCG must be initiated at least 2 weeks after TURBT or biopsy, and ideally 2-4 weeks, to avoid systemic absorption. 1

• For high-grade T1 patients requiring repeat resection at 4-6 weeks, delay BCG until after the second resection 1
• Never instill BCG in the presence of gross hematuria or active urinary tract infection—this can cause systemic BCG toxicity 1
• Asymptomatic bacteriuria does not require treatment delay and does not increase toxicity risk 1

Dosing Modifications

Full-dose BCG should be used for both induction and maintenance therapy. 1

• Dose reduction during maintenance may be necessary if side effects occur, using serial reductions to one-third, one-tenth, one-thirtieth, or one-hundredth of the standard dose 1
• The Oddens trial demonstrated efficacy hierarchy: full dose for 3 years > one-third dose for 3 years > full dose for 1 year > one-third dose for 1 year 1
• Modifications reducing the number of doses per maintenance session have NOT been shown to be beneficial 1
• During BCG shortages, starting induction with one-third dose to allow splitting among 3 patients is acceptable 1

Evidence Against Reduced Schedules

Reducing the number of BCG instillations below the standard SWOG schedule is inferior and should be avoided. 4

• The NIMBUS trial (2020) demonstrated that reducing from 15 to 9 total instillations resulted in significantly higher recurrence rates (46/170 vs 21/175 patients, HR 0.40,95% CI upper limit 0.68) 4
• The trial was stopped early due to inferiority of the reduced schedule 4
• Modified maintenance schedules (such as single instillations every 3 months) have consistently failed to show benefit 1

Minimum Effective Maintenance

At least 3 maintenance cycles are required to significantly reduce recurrence risk. 5

• Patients receiving ≥3 maintenance cycles had 89% recurrence-free survival at 12 months post-maintenance versus 41% for those receiving only induction (P = 0.0003) 5
• Patients receiving ≥3 maintenance cycles had significantly reduced recurrence risk (HR 0.23, P = 0.0064) compared to induction alone 5

Common Pitfalls to Avoid

• Do not use modified maintenance schedules (monthly single instillations, quarterly schedules)—these lack efficacy data 1
• Do not interchange BCG products—there are no data supporting interchangeability between TICE and Theracys 2
• Do not skip maintenance therapy—this is where much of the benefit for preventing progression occurs 1
• Do not give only 1 year of maintenance to high-risk patients—3 years is required for optimal outcomes 1
• Do not filter BCG suspension or use bacteriostatic solutions—use only preservative-free saline 2