Reduced- vs full-dose BCG in bladder cancer: A systematic review and meta-analysis

Verri, Paolo; Baboudjian, Michael; Diana, Pietro; Gallioli, Andrea; Territo, Angelo; Gaya, J.M.; Huguet, J.; Rodríguez-Faba, Óscar; Palou, Joan; Breda, Alberto

doi:10.1016/j.acuroe.2022.08.005

Cited by 5 publications

(3 citation statements)

References 36 publications

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“…Whether varying the BCG dose and revaccination could enhance trained immunity remains controversial. In bladder cancer treatment, there was an association of reduced BCG dose with recurrence but not with tumor progression, cancer-specific survival, and overall survival ( 68 , 69 ). Two clinical trials of BCG revaccination in children (who received neonatal BCG vaccination) aged 19 months and 7 to 14 years have shown that BCG revaccination provided greater protection against tuberculosis than a single dose ( 70 , 71 ).…”

Section: Discussionmentioning

confidence: 99%

Multi-omics analysis reveals that linoleic acid metabolism is associated with variations of trained immunity induced by distinct BCG strains

Xu,

Chen,

Huang

et al. 2024

Sci. Adv.

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Trained immunity is one of the mechanisms by which BCG vaccination confers persistent nonspecific protection against diverse diseases. Genomic differences between the different BCG vaccine strains that are in global use could result in variable protection against tuberculosis and therapeutic effects on bladder cancer. In this study, we found that four representative BCG strains (BCG-Russia, BCG-Sweden, BCG-China, and BCG-Pasteur) covering all four genetic clusters differed in their ability to induce trained immunity and nonspecific protection. The trained immunity induced by BCG was associated with the Akt-mTOR-HIF1α axis, glycolysis, and NOD-like receptor signaling pathway. Multi-omics analysis (epigenomics, transcriptomics, and metabolomics) showed that linoleic acid metabolism was correlated with the trained immunity–inducing capacity of different BCG strains. Linoleic acid participated in the induction of trained immunity and could act as adjuvants to enhance BCG-induced trained immunity, revealing a trained immunity–inducing signaling pathway that could be used in the adjuvant development.

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Section: Discussionmentioning

confidence: 99%

Multi-omics analysis reveals that linoleic acid metabolism is associated with variations of trained immunity induced by distinct BCG strains

Xu,

Chen,

Huang

et al. 2024

Sci. Adv.

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“…Another BCG dose reduction meta-analysis was published in 2023 [ 34 ]. The authors found that dose reduction did not affect progression, metastasis nor survival.…”

Section: Discussionmentioning

confidence: 99%

The Impact of Dose Reduction of Bacillus Calmette–Guerin on Oncological Outcomes and Toxicity in Non-Muscle Invasive Bladder Cancer: A Systematic Review and Meta-Analysis

Azuri,

Jaunarena,

Camean

et al. 2023

BLC

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BACKGROUND: Bacillus Calmette– Guerin (BCG) is the standard adjuvant treatment for intermediate and high-risk non-muscle invasive bladder cancer (NMIBC) following transurethral resection of the bladder (TURB). However, the optimal dose, strain, and schedule of BCG remain unclear. OBJECTIVE: To evaluate the impact of BCG dose reduction on oncological outcomes and toxicity in patients with non-muscle invasive bladder cancer. METHODS: We performed a systematic review of the literature in PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases. Selected studies were analyzed for Meta Analysis using PRISMA criteria. The study focused on disease recurrence, progression, and toxicity. We also compared the oncological outcomes of the different BCG strains. RESULTS: A total of 2963 patients in 13 randomized controlled trials were included. In recurrence analysis, we found a non-significant difference between the full dose and any dose reduction of BCG (HR = 1.17, [1.06–1.28], I2 = 0%, p = 0.7). In terms of progression, the difference was also non-statistically significant (HR: 1.12 [0.89 - 1.41], I2 = 0%, p = 0.93). In the toxicity analysis, there were more local (HR: 0.81 [0.67; 0.99] I2 = 76% ; p < 0.01) and systemic (HR: 0.53 [0.34; 0.82] I2 = 83% ; p < 0.01) side effects in the full dose group than in the dose reduction group. There were no statistically significant differences in oncological outcomes between the analyzed BCG strains. CONCLUSIONS: Dose reduction did not affect the oncological outcomes of patients with NMIBC who received adjuvant therapy with BCG. On the other hand, dose reduction showed a significant trend towards fewer systemic and local side effects. Further studies comparing oncological and toxicity outcomes using different strains are needed.

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“…A recent meta-analysis of 17 studies comprising 3,757 patients and multiple BCG strains showed increased recurrence rates with different regimens of RD BCG (1/3,1/2 and 2/3) (OR 1.19, 95% CI 1.03, 1.36; p = 0.02). However, this was no longer seen when maintenance therapy was administered (OR 1.07, 95% CI 0.96–1.29; p = 0.17) [ 13 ]. This was also confirmed by the NIMBUS trial where fewer instillations were associated with a higher risk of recurrence [ 14 ].…”

Section: Discussionmentioning

confidence: 99%

Comparative Analysis of Very Reduced vs Full Dose BCG Treatment for High-Risk Non-Muscle Invasive Bladder Cancer: A Contemporary Experience from Chile

Grajales,

Contieri,

Tan

et al. 2023

BLC

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BACKGROUND: Adjuvant bacillus Calmette-Guérin (BCG) is recommended for high-risk (HR) non-muscle invasive bladder cancer (NMIBC), but BCG shortages have led to exploration of reduced-dose regimens and shortened maintenance durations out of necessity, with limited data on treatment efficacy in Latin America. OBJECTIVE: Oncological outcomes of HR-NMIBC patients treated with reduced (RD,1/4th dose) vs full dose (FD) BCG instillations of Danish Strain 1331 BCG. METHODS: We performed a retrospective study of HR-NMIBC patients treated with BCG between 2003 and 2022 at our center in Santiago Chile. We stratified patients according to either RD (1/4th dose) or FD BCG. Univariate and multivariable Cox regression models were used to predict recurrence. Kaplan-Meier method was used to calculate survival estimates. RESULTS: Of a total of 200 patients, 116 (58%) had RD and 84 (42%) FD BCG. Median follow-up was 57 months (IQR: 29–100). Patients who received FD BCG had a lower risk of recurrence (HR: 0.41, 95% CI 0.22–0.74) and high-grade (HG)-recurrence (HR: 0.30, 95% CI 0.15–0.61; p = 0.001). More patients in the RD vs FD group progressed to MIBC (10/84 vs 2/116; p = 0.18). Additionally, patients were less likely to stop BCG treatment in the RD group compared to the FD group due to toxicity (5% vs 11%, p = 0.14). CONCLUSIONS: A 1/4th dose of Danish Strain 1331 BCG treatment was associated with worse recurrence free rate and HG-recurrence rate in our cohort. Patients with RD had lower discontinuation treatment rates due to a reduced toxicity profile. These findings would suggest that RD BCG would compromise oncological outcomes in HR-NMIBC patients.

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Reduced- vs full-dose BCG in bladder cancer: A systematic review and meta-analysis

Cited by 5 publications

References 36 publications

Multi-omics analysis reveals that linoleic acid metabolism is associated with variations of trained immunity induced by distinct BCG strains

Multi-omics analysis reveals that linoleic acid metabolism is associated with variations of trained immunity induced by distinct BCG strains

The Impact of Dose Reduction of Bacillus Calmette–Guerin on Oncological Outcomes and Toxicity in Non-Muscle Invasive Bladder Cancer: A Systematic Review and Meta-Analysis

Comparative Analysis of Very Reduced vs Full Dose BCG Treatment for High-Risk Non-Muscle Invasive Bladder Cancer: A Contemporary Experience from Chile

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