Comparison of Bacillus Calmette-Guérin Maintenance Therapy with Monthly Instillations and the Southwest Oncology Group Protocol in the Treatment of Non-muscle-invasive Bladder Cancer.

BACKGROUND: Bacillus Calmette-Guérin (BCG) therapy using the Southwest Oncology Group (SWOG) maintenance protocol is the standard in non-muscle-invasive bladder cancer (NMIBC). Maintenance with monthly instillations is also widely used, but evidence comparing the two maintenance protocols is scarce. OBJECTIVE: To compare monthly and SWOG instillation schedules in maintenance BCG therapy. DESIGN, SETTING, AND PARTICIPANTS: We retrospectively identified patients with NMIBC treated with maintenance BCG according to either the monthly or the SWOG instillation regimen in two tertiary care centers in Finland between 2009 and 2019. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We compared discontinuation rates of the monthly and SWOG maintenance protocols due to toxicity, and recurrence and progression rates by protocols. Baseline characteristics were compared with the Wilcoxon rank sum test, chi-square test, and Fisher's exact test. The Kaplan-Meier method and Cox proportional hazards model were used to evaluate the discontinuation of BCG due to toxicity and oncological efficacy. RESULTS AND LIMITATIONS: We identified 723 patients, of whom 545 (75%) and 178 (25%) received maintenance according to the monthly and SWOG protocols, respectively. The median follow-up time was 66 (interquartile range: 45-99) mo. In the monthly and SWOG groups, 131 (24%) and 50 (28%) patients, respectively, discontinued BCG due to toxicity, with no difference in a univariate or multivariate analysis (hazard ratio 1.01, 95% confidence interval [CI]: 0.73-1.40, p = 0.940). The 5-yr recurrence-free survival rates in the monthly and SWOG groups were 65% (95% CI: 61-69%) and 71% (95% CI: 64-79%, p = 0.370), respectively. The 5-yr progression-free survival rates were 89% (95% CI: 86-92%) and 91% (95% CI: 86-96%, p = 0.240), respectively. CONCLUSIONS: Monthly maintenance is a comparable alternative to the SWOG protocol. PATIENT SUMMARY: In this study, we compared two schedules of intravesical bacillus Calmette-Guérin (BCG) treatment used in the treatment of non-muscle-invasive bladder cancer. We found that there were no significant differences between the two instillation schedules in terms of tolerability or efficacy.

Incidence of and mortality from Bacille Calmette-Guérin (BCG) infections after BCG instillation therapy.

OBJECTIVES: To investigate the incidence of and mortality associated with Bacille Calmette-Guérin (BCG) infections in a Finnish population of patients with bladder cancer treated with BCG instillations. MATERIALS AND METHODS: We conducted a nationwide register study and identified patients with BCG infections in Finland during 1996 to 2016 using the Finnish Cancer Registry and the Finnish National Infectious Diseases Register. We estimated the number of patients treated with BCG instillations based on data on national consumed BCG doses used to treat patients with bladder cancer, and calculated the annual incidence proportion of BCG infections. We further performed a detailed medical chart review to describe the clinical features and outcomes of the treated BCG infections. RESULTS: In total, 87 patients with BCG infection after BCG treatment of bladder cancer were identified. The incidence proportion increased gradually, yielding a cumulative incidence proportion of 2.5% during the latter half of the study period. BCG infections led to significant mortality, with 10% overall mortality and 17.5% mortality from systemic infections, which is notably higher than previously reported. CONCLUSION: The incidence proportion of BCG infections among bladder cancer patients treated with BCG has increased in Finland up to 2.5% at a nationwide level, with a notably higher mortality rate than previously reported.

A retrospective study on tolerability and complications of bacillus Calmette-Guérin (BCG) instillations for non-muscle-invasive bladder cancer.

Objectives: The objective was to evaluate the tolerability of BCG treatment and to evaluate the effects of interruption on treatment outcomes. The incidence and characteristics of severe complications were observed. Methods: From hospital records, all bladder carcinoma patients treated with BCG instillations in the institution from 2009-2015 were retrospectively identified. The reasons for interruption, treatment outcome, number of instillations, and diagnosis of BCG infection were recorded. Results: Of the 418 patients who started BCG instillation therapy, 176 (42.1%) interrupted BCG treatment. Of those, 23 (5.5%) patients interrupted because of suspected BCG infection. Systemic BCG infection was found in seven (1.7%), and local infection in five (1.2%) patients. Interruption of treatment was due to other adverse effects in 71 patients (17.0%), BCG failure in 46 patients (11.0%), and other reasons in 36 patients (8.6%). Fifty percent of interruptions due to adverse effects occurred within the first 6 months. The probabilities of tumor recurrence (20.0% vs 10.7%, p = 0.014, OR = 2.077, CI95% = 1.149-3.753) and disease progression (5.4% vs 1.2%, p = 0.018, OR = 4.534, CI95% = 1.152-17.840) were higher among patients whose BCG treatment was interrupted. Conclusions: Severe complications were encountered in only <5% of patients. Adverse effects requiring treatment interruption were more likely to happen within the first year of treatment. Interrupting BCG treatment due to adverse effects increased the risk of disease progression and tumor recurrence.