TICE strain Bacillus of Calmette-Guerin 12.5mg powder for reconstitution for instillation vials

BackgroundMost patients with localized bladder cancer are initially managed with endoscopic resection. For high-grade nonmuscle invasive bladder cancer (NMIBC), intravesical Bacillus Calmette-Guerin (BCG) therapy is the gold standard adjuvant treatment. However, 30%-40% of patients fail BCG treatment with lack of response or disease relapse. An understudied area of treatment failure is BCG intolerance, where patients drop out of treatment due to adverse effects.ObjectivesTo examine the incidence and underlying reasons for BCG intolerance among adult patients with NMIBC.MethodsWe conducted a search on Embase, MEDLINE, and Cochrane Central Register of Controlled Trials for studies from January 1, 1974 to January 10, 2023, retrieving 3340 articles. Two authors independently conducted screening and data extraction with Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Inclusion criteria include English-language studies reporting dropout rates and reasons for discontinuation of BCG therapy in NMIBC patients.ResultsBCG dropout rates reported among the 28 included studies varied widely from 0% to 52% (estimated summary proportion 12.8%, 95% CI 9%-17%). There was significant heterogeneity in study design. Subgroup analyses show a dose-dependent effect on dropout rates (3.3% vs. 20%, X2 = 83.6, p = -16). Dropout rates vary with BCG strains: the Connaught strain had the highest at 21.1%, while the Pasteur strain had 2%. Clinical outcomes for BCG intolerance are not widely reported.ConclusionsDropout rates due to BCG intolerance average 12.8%. As cessation of treatment could lead to an increased risk in progression or recurrence of disease, strategies to mitigate BCG intolerance would be valuable.

Abstract licence: CC BY-NC-ND

ImportanceDue to the ongoing bacillus Calmette-Guérin (BCG) shortage, sequential intravesical gemcitabine and docetaxel has been increasingly used as first-line therapy for high-risk non-muscle-invasive bladder cancer (NMIBC). However, data directly comparing these 2 therapies are lacking.ObjectiveTo compare the outcomes of patients with high-risk NMIBC treated with gemcitabine and docetaxel vs BCG.Design, setting, and participantsThis retrospective cohort study was conducted from January 1, 2011, to December 31, 2021. The median (IQR) duration of follow-up was 23 (12-33) months for patients receiving gemcitabine and docetaxel and 49 (27-79) months for patients receiving BCG. All patients were treated at the University of Iowa tertiary care center. A total of 312 patients with high-risk treatment-naive NMIBC were included; 174 patients were treated with BCG therapy and 138 were treated with gemcitabine and docetaxel therapy.ExposuresAfter undergoing complete transurethral resection of bladder tumor, patients received either sequential intravesical gemcitabine, 1 g, and docetaxel, 37.5 mg, or 1 vial of BCG. Induction treatments were administered once per week for 6 weeks. Maintenance regimens were initiated if the patient was disease free at the first follow-up visit.Main outcomes and measuresThe primary outcome was high-grade recurrence-free survival (RFS). Survival probabilities were estimated using the Kaplan-Meier method. Cox regression models were used to evaluate the association of covariates with outcomes. Adverse events were reported using the Common Terminology Criteria for Adverse Events, version 5.ResultsAmong 312 patients, the median (IQR) age was 73 (66-79) years; 255 patients (81.7%) were male and 292 (93.6%) were White. Baseline clinicopathological characteristics such as sex, smoking status, and pretreatment tumor pathology were similar between treatment groups. High-grade RFS estimates were 76% (95% CI, 69%-82%) at 6 months, 71% (95% CI, 64%-78%) at 12 months, and 69% (95% CI, 62%-76%) at 24 months in the BCG group and 92% (95% CI, 86%-95%) at 6 months, 85% (95% CI, 78%-91%) at 12 months, and 81% (95% CI, 72%-87%) at 24 months in the gemcitabine and docetaxel group. Multivariable Cox regression analyses controlled for age, sex, treatment year, and presence of carcinoma in situ revealed that treatment with gemcitabine and docetaxel was associated with better high-grade RFS (hazard ratio, 0.57; 95% CI, 0.33-0.97; P = .04) and RFS (hazard ratio, 0.56; 95% CI, 0.34-0.92; P = .02) than treatment with BCG. Induction therapy for BCG was associated with greater treatment discontinuation than induction therapy for gemcitabine and docetaxel (9.2% vs 2.9%; P = .02).Conclusions and relevanceIn this cohort study, gemcitabine and docetaxel therapy was associated with less high-grade disease recurrence and treatment discontinuation than BCG therapy. These findings suggest that, while awaiting results from an ongoing randomized clinical trial during the current BCG shortage, use of gemcitabine and docetaxel can be considered for recommendation in updated practice guidelines.

Abstract licence: CC BY