Connaught strain Bacillus of Calmette-Guerin 81mg powder for reconstitution for instillation vials

The South West Oncology Group's 2000 randomised-control trial investigated the addition of maintenance intravesical bacillus Calmette-Guerin (BCG) to non-muscle invasive urothelial carcinoma (NMIUC) treatment. The results were published when the efficacy of BCG immunotherapy maintenance was unclear.Randomisation produced two arms, each containing 192 patients assessed to be at high risk of recurrence following induction BCG therapy for NMIUC. The treatment arm went on to receive three successive weekly intravesical and percutaneous BCG administrations at three months, six months and then six monthly for three years from the start of induction therapy.Recurrence free-survival (RFS), was higher in the maintenance arm with 41% (95%CI 35-49) RFS at five years in the control arm and 60% RFS (53-67 95% CI) in the maintenance arm (p < 0.0001). Only 16% of patients in the treatment arm received all of the scheduled maintenance courses of BCG.The study's seminal results correlate with contemporary systematic review and have guided international guidelines.

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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.

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IntroductionThe Bacillus Calmette-Guerin (BCG) vaccine has a beneficial "off-target" effect that offers heterologous protection against respiratory tract infections by inducing trained immunity. The need for producing antigen-specific COVID-19 vaccines leads to delays in vaccine administration. Current randomized controlled trials (RCTs) report conflicting data on BCG's efficacy in COVID-19 infection.MethodsA comprehensive literature search was conducted using major bibliographic databases to identify RCTs evaluating the outcomes of BCG re-vaccination in COVID-19. For dichotomous outcomes, odds ratios (ORs) with 95% CIs were pooled using the DerSimonian-Laird random-effects model. Statistical significance was set at P less than 0.05.ResultsThirteen RCTs with 13 939 participants (7004 in the BCG re-vaccination group and 6935 in the placebo group) were included. BCG re-vaccination did not lead to a statistically significant difference in the incidence of COVID-19 infection [OR: 1.04; 95% CI: 0.91, 1.19; P=0.56], COVID-19-related hospitalizations [OR: 0.81; 95% CI: 0.38, 1.72; P=0.58), ICU admissions [OR: 0.43; 95% CI: 0.13, 1.46; P=0.18], or mortality [OR: 0.67; 95% CI 0.15, 3.04; P=0.60]. For safety outcomes, BCG re-vaccination led to a significant increase in the local injection site complications [OR: 99.79; 95% CI: 31.04, 320.80; PP=0.33].ConclusionsBCG re-vaccination does not decrease the incidence of COVID-19 infection, COVID-19-related hospitalizations, ICU admissions, COVID-19-related mortality, and serious adverse events; however, it leads to a rise in local injection site complications. Caution should be exercised when overstating BCG's efficacy in COVID-19 prevention.

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