Final results from a national multicenter phase II trial of combination bacillus Calmette-Guérin plus interferon α-2B for reducing recurrence of superficial bladder cancer☆

Joudi, Fadi N.; Smith, Brian J.; O’Donnell, Michael A.

doi:10.1016/j.urolonc.2005.11.026

Cited by 220 publications

(133 citation statements)

References 7 publications

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“…The current strategy for follow-up treatment is based on risk stratification, dependent on recurrence and progression scores (14). In clinical trial, bacillus Calmette-Guérin in combination with IFN alpha-2B has been shown to be effective in reducing the recurrence and progression (23). Genetic markers can be of utmost use in stratification of at risk patients.…”

Section: Discussionmentioning

confidence: 99%

TERT promoter mutations in bladder cancer affect patient survival and disease recurrence through modification by a common polymorphism

Rachakonda

Hosen

Verdier

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

299

343

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The telomerase reverse transcriptase (TERT) promoter, an important element of telomerase expression, has emerged as a target of cancer-specific mutations. Originally described in melanoma, the mutations in TERT promoter have been shown to be common in certain other tumor types that include glioblastoma, hepatocellular carcinoma, and bladder cancer. To fully define the occurrence and effect of the TERT promoter mutations, we investigated tumors from a well-characterized series of 327 patients with urothelial cell carcinoma of bladder. The somatic mutations, mainly at positions −124 and −146 bp from ATG start site that create binding motifs for E-twenty six/ternary complex factors (Ets/TCF), affected 65.4% of the tumors, with even distribution across different stages and grades. Our data showed that a common polymorphism rs2853669, within a preexisting Ets2 binding site in the TERT promoter, acts as a modifier of the effect of the mutations on survival and tumor recurrence. The patients with the mutations showed poor survival in the absence [hazard ratio (HR) 2.19, 95% confidence interval (CI) 1.02-4.70] but not in the presence (HR 0.42, 95% CI 0.18-1.01) of the variant allele of the polymorphism. The mutations in the absence of the variant allele were highly associated with the disease recurrence in patients with Tis, Ta, and T1 tumors (HR 1.85, 95% CI 1.11-3.08). The TERT promoter mutations are the most common somatic lesions in bladder cancer with clinical implications. The association of the mutations with patient survival and disease recurrence, subject to modification by a common polymorphism, can be a unique putative marker with individualized prognostic potential.TERT mutations | cancer genetics | transcription factors | noncoding mutations | reporter assays T he human telomerase reverse transcriptase (TERT) gene encodes the catalytic reverse transcriptase subunit of telomerase that maintains telomere length (1). Increased telomerase activity is perceived to be one of the hallmarks of human cancers, and the transcriptional regulation of the TERT gene is the major cause of its cancer-specific activation (2, 3). The TERT promoter has been shown to be the most important element of telomerase expression because it harbors binding sites for numerous cellular transcriptional activators and repressors that directly or indirectly regulate the gene expression (4). In addition, the high GC content around the transcription start site of the TERT promoter confers epigenetic regulation through methylation and chromatin remodeling (5, 6).We previously described a high-penetrant disease segregating single-nucleotide germ-line mutation in the TERT promoter in a large melanoma family (7). The A > C (T > G) mutation at position −57 bp (from the ATG start site; Chr 5:1295161 hg19 coordinate) resulted in creation of a new binding motif GGAA/T for E-twenty six (Ets) transcription factors and a general binding CCGGAA/T motif for ternary complex factors (TCF) (8). Simultaneous screening of the TERT promoter for somatic mutations...

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Section: Discussionmentioning

confidence: 99%

TERT promoter mutations in bladder cancer affect patient survival and disease recurrence through modification by a common polymorphism

Rachakonda

Hosen

Verdier

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

299

343

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“…Recently, the addition of a single 3 week maintenance course of BCG increased the complete response rate at 6 months from 68% to 84% compared to patients who receive only a 6-week induction course [4]. The addition of interferon alpha may augment the response to BCG and Phase II studies suggest that salvage of high risk patients who have failed BCG is possible in over one half of patients treated with this combination [5,6].…”

Section: Introductionmentioning

confidence: 99%

Failure to achieve a complete response to induction BCG therapy is associated with increased risk of disease worsening and death in patients with high risk non-muscle invasive bladder cancer

Lerner

Tangen

Sucharew

et al. 2009

Urologic Oncology: Seminars and Original Investigations

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Purpose-The Southwest Oncology Group conducted a randomized trial of induction BCG with or without maintenance BCG. In these additional retrospective analyses, our goal was to evaluate the association of a complete response (CR) or remaining with no evidence of disease (NED) versus no CR during induction therapy with subsequent survival after adjusting for other potential confounders. Among all patients randomized to maintenance treatment, we also wanted to identify combinations of baseline covariates in order to define prognostic groups for subsequent worseningfree survival.Methods-Outcome measures of worsening-free and overall survival were assessed using Kaplan Meier estimates and proportional hazards regression models. For the Classification and Regression Tree (CART) analysis, 434 patients randomized to maintenance vs. no therapy with complete covariate information were included.Results-Of the 593 evaluable patients, 341 were not randomized to maintenance BCG. Patients who achieved a prior complete response during induction BCG had a 5-year survival probability of 77% compared to 62% for patients who did not [Hazard ratio (HR) 0.60; 95% confidence interval (CI) 0.44, 0.81; p= 0.0008]. Prior CR retained significance when adjusted for age, gender, prior intravesical chemotherapy, and papillary disease versus CIS (HR=0.63; 95% CI: .46, .86; p=0.003). CART analysis identified 4 prognostic groups. Older patients (≥ 62 years old) previously treated with intravesical chemotherapy who failed to achieve a CR had a 5-fold higher risk of a worsening event relative to those who are younger (< 67 years old) and achieve a CR (HR=5.09; 95% CI: 3.37, 7.68; p<0.0001). Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Conclusion-Failure to achieve a complete response after induction BCG is associated with a significant risk of a worsening event and death for patients with CIS or Ta or T1 bladder cancer at increased risk of recurrence. NIH Public Access

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“…BCG therapy seems to be the binding of mycobacteria to the urothelial lining, which depends on the interaction of a fibronectin attachment protein on the bacterial surface with the fibronectin in the bladder wall. The presence of BCG then leads to the activation of urothelial and antigen-presenting cells 9 . Evidence to date supports the idea that the antitumor effects of BCG are produced by an interplay between the direct effects on tumor cells by BCG infection and the host's immune response 8 .…”

Section: Mechanism Of Action Of Bcgmentioning

confidence: 99%

“…After these events, a massive cellular infiltration is seen, and this local inflammatory reaction in the bladder mucosa is characterized by large numbers of T cells, both CD4 and CD8, as well as macrophages 2 . The result of this immune activation is to improve recognition and subsequent destruction of tumor cells through non-specific and specific cell-mediated mechanisms 9 . Only viable BCG organisms can induce the activity of the killer cells.…”

Section: Mechanism Of Action Of Bcgmentioning

confidence: 99%

BCG Immunotherapy for Bladder Carcinoma

Mallik¹,

Rahman²,

Halder³

2017

KYAMC j.

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Purpose: We reviewed the literatures to see history, regimen of BCG and how BCG become a standard therapy for bladder carcinoma.Materials and Methods: We reviewed the previous literature describing the bacillus Calmette-Guerin (BCG) vaccine as an anticancer agent and its success as the most effective immunotherapy used against human bladder cancer and its adverse effects.Results: The association between tuberculosis and carcinoma is well established, It demonstrate that Bacillus Calmette-Guerin have immunological reactivity, inhibiting the tumor growth and progression in experimental animal models, led to clinical trials showing that intravesical Bacillus Calmette-Guerin eradicate and prevent recurrence and progression of superficial bladder carcinoma The exact mechanism of action of intravesical BCG instillation is still under investigation. However, it appears that BCG is mediated by the local immune response, mainly through T-helper cell response. It reduces the recurrence rate by an average of 40% and progression by more than 20% in papillary tumors, Carcinoma-in-situ over the patients without BCG therapy.Conclusions: For the last 45 yrs Bacillus Calmette- Guerin therapy has remained first line intravesical immunotherapy for superficial bladder cancer, an outstanding example of successful immunotherapy.KYAMC Journal Vol. 8, No.-1, Jul 2017, Page 56-60

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Final results from a national multicenter phase II trial of combination bacillus Calmette-Guérin plus interferon α-2B for reducing recurrence of superficial bladder cancer☆

Cited by 220 publications

References 7 publications

TERT promoter mutations in bladder cancer affect patient survival and disease recurrence through modification by a common polymorphism

TERT promoter mutations in bladder cancer affect patient survival and disease recurrence through modification by a common polymorphism

Failure to achieve a complete response to induction BCG therapy is associated with increased risk of disease worsening and death in patients with high risk non-muscle invasive bladder cancer

BCG Immunotherapy for Bladder Carcinoma

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