BCG in Bladder Cancer Immunotherapy

Jiang, Siwei; Redelman-Sidi, Gil

doi:10.3390/cancers14133073

Cited by 54 publications

(53 citation statements)

References 136 publications

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“…In our study, we did not find any consistent differences in the relative efficacy of the BCG strains adopted both at per cumulative event rate level stratified by RFS timepoints and at the network metanalysis of the direct and indirect treatment comparisons. This was also true when comparing our outcomes to those previously published in other series [ 88 , 89 , 90 , 91 ]. However, at a closer analysis of our results, BCG Tokyo 172 was the sole exhibiting a relatively lower percentage of pooled BC recurrence (i.e., 0.22, 95%CI 0.16–0.27) but only in the 1 to 3 years RFS time points, yet this not translated in any BCG contrasts superiority at network assessment ( Figure 3 ).…”

Section: Discussionsupporting

confidence: 84%

Efficacy of Different Bacillus of Calmette-Guérin (BCG) Strains on Recurrence Rates among Intermediate/High-Risk Non-Muscle Invasive Bladder Cancers (NMIBCs): Single-Arm Study Systematic Review, Cumulative and Network Meta-Analysis

Giudice

Asero

Bologna

et al. 2023

Cancers

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Background: In an era of Bacillus of Calmette-Guérin (BCG) shortages, the comparative efficacy from different adjuvant intravesical BCG strains in non-muscle invasive bladder cancer (NMIBC) has not been clearly elucidated. We aim to compare, through a systematic review and meta-analysis, the cumulative BC recurrence rates and the best efficacy profile of worldwide available BCG strains over the last forty years. Methods: PubMed, Scopus, Web of Science, Embase, and Cochrane databases were searched from 1982 up to 2022. A meta-analysis of pooled BC recurrence rates was stratified for studies with ≤3-y vs. >3-y recurrence-free survival (RFS) endpoints and the strain of BCG. Sensitivity analysis, sub-group analysis, and meta-regression were implemented to investigate the contribution of moderators to heterogeneity. A random-effect network meta-analysis was performed to compare BCG strains on a multi-treatment level. Results: In total, n = 62 series with n = 15,412 patients in n = 100 study arms and n = 10 different BCG strains were reviewed. BCG Tokyo 172 exhibited the lowest pooled BC recurrence rate among studies with ≤3-y RFS (0.22 (95%CI 0.16–0.28). No clinically relevant difference was noted among strains at >3-y RFS outcomes. Sub-group and meta-regression analyses highlighted the influence of NMIBC risk-group classification and previous intravesical treated categories. Out of the n = 11 studies with n = 7 BCG strains included in the network, BCG RIVM, Tice, and Tokyo 172 presented with the best-predicted probability for efficacy, yet no single strain was significantly superior to another in preventing BC recurrence risk. Conclusion: We did not identify a BCG stain providing a clinically significant lower BC recurrence rate. While these findings might discourage investment in future head-to-head randomized comparison, we were, however, able to highlight some potential enhanced benefits from the genetically different BCG RIVM, Tice, and Tokyo 172. This evidence would support the use of such strains for future BCG trials in NMIBCs.

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Section: Discussionsupporting

confidence: 84%

Efficacy of Different Bacillus of Calmette-Guérin (BCG) Strains on Recurrence Rates among Intermediate/High-Risk Non-Muscle Invasive Bladder Cancers (NMIBCs): Single-Arm Study Systematic Review, Cumulative and Network Meta-Analysis

Giudice

Asero

Bologna

et al. 2023

Cancers

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“…It is widely accepted that BCG stimulates the immune system leading to anti-tumour activity driven by several cytokines and chemokines, which lead to the recruitment of immune system cells (granulocytes, CD4 + and CD8 + T cells, macrophages, and natural killer) [16,17]. Therefore, it has been hypothesised that immunology-based BCG anti-tumour activity is weaker in elderly patients.…”

Section: Discussionmentioning

confidence: 99%

Impact of age >70 years on oncological outcomes in patients with non‐muscle‐invasive bladder cancer treated with Bacillus Calmette–Guérin

et al. 2023

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ObjectiveTo evaluate the impact of age on oncological outcomes in a large contemporary cohort of patients with non‐muscle‐invasive bladder cancer (NMIBC) treated with adequate Bacillus Calmette–Guérin (BCG).Patients and MethodsWe performed an Institutional Review Board‐approved retrospective study analysing patients with NMIBC treated with adequate BCG at our institution from 2000 to 2020. Adequate BCG was defined as per United States Food and Drug Administration (FDA) guidelines as being receipt of at least five of six induction BCG instillations with a minimum of two additional doses (of planned maintenance or of re‐induction) of BCG instillations within a span of 6 months. The study's primary outcome was to determine if age >70 years was associated with progression to MIBC cancer or distant metastasis. The cumulative incidence method and the competing‐risk regression analyses were used to investigate the association of advanced age (>70 years) with progression, high‐grade (HG) recurrence and cancer‐specific mortality (CSM).ResultsOverall, data from 632 patients were analysed: 355 patients (56.2%) were aged ≤70 years and 277 (43.8%) were >70 years. Age >70 years did not adversely affect either cumulative incidence of progression or HG recurrence (P = 0.067 and P = 0.644, respectively). On competing‐risk regression analyses, age >70 years did not emerge as an independent predictor of progression or HG recurrence (sub‐standardised hazard ratio [SHR] 1.57, 95% confidence interval [CI] 0.87–2.81, P = 0.134; and SHR 1.05, 95% CI 0.77–1.44, P = 0.749). Not unexpectedly, patients in the older group did have higher overall mortality (P < 0.001) but not CSM (P = 0.057).ConclusionAge >70 years was not associated with adverse oncological outcomes in a large contemporary cohort of patients receiving adequate intravesical BCG for NMIBC. BCG should not be withheld from older patients seeking for bladder sparing options.

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“…However, many patients with high-risk NMIBC undergo intravesical BCG instillation. Because BCG treatment is considered highly effective, the risk of recurrence is strongly dependent on whether or not this treatment is administered [ 23 , 24 ]. BCG treatment must be carefully considered when discussing postoperative recurrence of NMIBC with reference to guidelines.…”

Section: Discussionmentioning

confidence: 99%

Relationship between Preoperative Pyuria and Bacille Calmette-Guerin Treatment in Intravesical Recurrence after Transurethral Resection of High-Risk, Non-Muscle Invasive, Bladder Carcinoma: A Retrospective Study of Human Data

Tsukamoto

Sazuka

Hattori

et al. 2023

Cancers

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Some researchers have found that preoperative pyuria is a risk factor for recurrence after transurethral resection of high-risk non-muscle invasive bladder cancer. However, to our knowledge, none have clarified the risks associated with pyuria according to bacille Calmette-Guerin (BCG) treatment status. We retrospectively selected patients with high-risk non-muscle invasive bladder cancer according to Japanese Urological Association guidelines. Pyuria was defined as ≥10 white blood cells per high-powered field. We analyzed recurrence-free rates (RFS) in 424 patients who had and had not undergone BCG treatment. The median duration of follow-up was 45.2 months. According to multivariate analysis, postoperative intravesical BCG induction and preoperative pyuria were independent risk factors for intravesical recurrence in the whole study cohort. We found no significant risk factors for recurrence in the BCG-treated group (n = 179). In the non-BCG-treated group (n = 245), patients with pyuria were much more frequently female and more often had T1 disease than patients without pyuria. According to univariate and multivariate analysis, preoperative pyuria is an independent risk factor for intravesical recurrence. There was no significant difference in the severity of pyuria between the BCG and non-BCG-treated groups. Aggressive BCG treatment may need to be considered in patients with high-risk NMIBC and pyuria.

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BCG in Bladder Cancer Immunotherapy

Cited by 54 publications

References 136 publications

Efficacy of Different Bacillus of Calmette-Guérin (BCG) Strains on Recurrence Rates among Intermediate/High-Risk Non-Muscle Invasive Bladder Cancers (NMIBCs): Single-Arm Study Systematic Review, Cumulative and Network Meta-Analysis

Efficacy of Different Bacillus of Calmette-Guérin (BCG) Strains on Recurrence Rates among Intermediate/High-Risk Non-Muscle Invasive Bladder Cancers (NMIBCs): Single-Arm Study Systematic Review, Cumulative and Network Meta-Analysis

Impact of age >70 years on oncological outcomes in patients with non‐muscle‐invasive bladder cancer treated with Bacillus Calmette–Guérin

Relationship between Preoperative Pyuria and Bacille Calmette-Guerin Treatment in Intravesical Recurrence after Transurethral Resection of High-Risk, Non-Muscle Invasive, Bladder Carcinoma: A Retrospective Study of Human Data

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