scholarly journals Nonmuscle invasive urothelial cancer— Bacillus Calmette–Guérin instillation or checkpoint inhibitor immunotherapy?

2019 ◽  
Vol 12 (4) ◽  
pp. 319-323 ◽  
Author(s):  
Stephan Brönimann ◽  
Shahrokh F. Shariat ◽  
Melanie R. Hassler
Keyword(s):  
Bladder Cancer ◽  
Immune System ◽  
Cancer Patients ◽  
Checkpoint Inhibitor ◽  
Significant Proportion ◽  
Intravesical Instillation ◽  
Bacillus Calmette Guerin ◽  
Bcg Immunotherapy ◽  
Clinical Scenarios ◽  
Bcg Therapy

Summary To date, intravesical instillation of Bacillus Calmette–Guérin (BCG) is the standard adjuvant treatment for most intermediate- and all high-risk bladder nonmuscle invasive urothelial carcinomas (NMIBC) after complete transurethral resection. Although BCG immunotherapy successfully reduces both recurrence and progression rates in affected patients, there are certain limitations associated with its application. Major issues are the relatively high failure rate in up to 40% of patients, the adverse effects of the instillations, and the shortage in BCG supply, requiring concerted alternative strategies. Furthermore, radical cystectomy, the currently suggested salvage treatment for patients failing BCG therapy, is often an overtreatment for a significant proportion of patients. Checkpoint inhibitor (CKI) immunotherapy has proven to be highly effective in a subset of advanced bladder cancer patients and is currently tested in various clinical scenarios alone and in combination with BCG in the adjuvant setting. CKIs’ mechanism is to a large part similar to that reported for BCG—that is, activation of the immune system and elimination of cancer cells in the bladder. Furthermore, CKIs could synergistically enhance the effect of the immune system attracted by BCG and are generally associated with acceptable rates of adverse reactions. Thus, they may represent an ideal alternative to or partner for BCG immunotherapy in NMIBC. In case the recent encouraging results of currently ongoing trials translate into tangible improved outcomes, the combination of CKI and BCG immunotherapy can be expected to represent a valid treatment strategy for well-selected nonmuscle invasive bladder cancer patients in the future.

scholarly journals Clinical Spectrum of Complications Induced by Intravesical Immunotherapy of Bacillus Calmette-Guérin for Bladder Cancer

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Yuqing Liu ◽  
Jian Lu ◽  
Yi Huang ◽  
Lulin Ma
Keyword(s):  
Bladder Cancer ◽  
Adverse Reactions ◽  
Clinical Manifestations ◽  
Bacillus Calmette Guerin ◽  
Bcg Immunotherapy ◽  
Bcg Therapy ◽  
Intravesical Bcg ◽  
Proven Efficacy ◽  
Bcg Instillation ◽  
Early Establishment

Because of its proven efficacy, intravesical Bacillus Calmette-Guérin (BCG) immunotherapy is an important treatment for nonmuscle invasive bladder cancer at high risk of recurrence or progression. However, approximately 8% of patients have to stop BCG instillation as a result of its complications. Complications induced by BCG therapy can have a variety of clinical manifestations. These adverse reactions may occur in conjunction with BCG instillation or may not develop until months or years after BCG cessation. An essential step in the management complications arising from BCG is early establishment of diagnosis, particularly for distant, disseminated, and obscure infections. Therefore we reviewed the literature on the potential complications after intravesical BCG immunotherapy for bladder cancer and provide an overview on the incidence, diagnosis, and treatment modality of genitourinary and systemic BCG-induced complications.

scholarly journals Bacillus Calmette-Guérin (BCG) therapy lowers the incidence of Alzheimer’s disease in bladder cancer patients

PLoS ONE ◽  
2019 ◽  
Vol 14 (11) ◽  
pp. e0224433 ◽  
Author(s):  
Ofer N. Gofrit ◽  
Benjamin Y. Klein ◽  
Irun R. Cohen ◽  
Tamir Ben-Hur ◽  
Charles L. Greenblatt ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Bladder Cancer ◽  
Cancer Patients ◽  
Bacillus Calmette Guerin ◽  
Bcg Therapy

Effectiveness of the Moreau strain of Bacillus Calmette-Guerin (BCG) for nonmuscle invasive bladder cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 4539-4539 ◽  
Author(s):  
Daher Cezar Chade ◽  
Andre Machado ◽  
Ricardo Waksman ◽  
Guilherme Garcia ◽  
Paulo Esteves ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
High Risk ◽  
Disease Progression ◽  
Disease Recurrence ◽  
Intravesical Instillation ◽  
Bacillus Calmette Guerin ◽  
Free Survival ◽  
Instillation Therapy ◽  
Bcg Therapy ◽  
Muscle Invasive

4539 Background: Intravesical instillation therapy of Bacillus Calmette-Guerin (BCG) for intermediate and high-risk non-muscle invasive bladder cancer (NMIBC) after complete transurethral resection has been widely shown to be more effective than any other adjuvant treatment. However, there are several different BCG strains not appropriately evaluated in clinical setting, but in current use. BCG Moreau is by far the most utilized strain in Brazil and has been recently introduced to the European market to cover the issue of BCG shortage, but there is insufficient data regarding its oncologic efficacy. Methods: We retrospectively analyzed 336 consecutive patients, who received adjuvant intravesical instillation therapy with BCG Moreau for intermediate- and high-risk NMIBC between January 2005 and February 2015 at a single institution. The end points of this study were time to first recurrence and progression to muscle-invasive disease. Results: Median age was 62 years (interquartile range 54-76, mean 64.3 years). In addition to induction BCG therapy, 228 (67.9%) patients received maintenance BCG. However, 35 (15.4%) patients interrupted maintenance BCG due to toxicity. Overall, after at least a complete induction BCG therapy, 87 (25.9%) patients presented with disease recurrence and 33 (9.8%) patients had disease progression. When analyzing on patients who received BCG maintenance in addition to induction therapy, 31 (13.6%) patients had disease recurrence and 10 (4.4%) had disease progression. The 5-year recurrence-free survival and progression-free survival rate was 69.8% (95% CI 52.8-77.2) and 86.2% (95% CI 69.9-93.2), respectively. Conclusions: BCG Moreau has shown to be safe and effective as adjuvant intravesical treatment in intermediate and high-risk NMIBC patients. Since results are comparable to other strains, wider use of BCG Moreau may be encouraged and prospective clinical trials stimulated for higher level of evidence.

scholarly journals Identification of NOTCH4 mutation as a response biomarker for immune checkpoint inhibitor therapy

BMC Medicine ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Junyu Long ◽  
Dongxu Wang ◽  
Xu Yang ◽  
Anqiang Wang ◽  
Yu Lin ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Bladder Cancer ◽  
Cancer Patients ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Small Cell ◽  
Small Cell Lung ◽  
Esophagogastric Cancer ◽  
Clinical Benefits

Abstract Background Immune checkpoint inhibitor (ICI) therapy elicits durable antitumor responses in patients with many types of cancer. Genomic mutations may be used to predict the clinical benefits of ICI therapy. NOTCH homolog-4 (NOTCH4) is frequently mutated in several cancer types, but its role in immunotherapy is still unclear. Our study is the first to study the association between NOTCH4 mutation and the response to ICI therapy. Methods We tested the predictive value of NOTCH4 mutation in the discovery cohort, which included non-small cell lung cancer, melanoma, head and neck squamous cell carcinoma, esophagogastric cancer, and bladder cancer patients, and validated it in the validation cohort, which included non-small cell lung cancer, melanoma, renal cell carcinoma, colorectal cancer, esophagogastric cancer, glioma, bladder cancer, head and neck cancer, cancer of unknown primary, and breast cancer patients. Then, the relationships between NOTCH4 mutation and intrinsic and extrinsic immune response mechanisms were studied with multiomics data. Results We collected an ICI-treated cohort (n = 662) and found that patients with NOTCH4 mutation had better clinical benefits in terms of objective response rate (ORR: 42.9% vs 25.9%, P = 0.007), durable clinical benefit (DCB: 54.0% vs 38.1%, P = 0.021), progression-free survival (PFS, hazard ratio [HR] = 0.558, P < 0.001), and overall survival (OS, HR = 0.568, P = 0.006). In addition, we validated the prognostic value of NOTCH4 mutation in an independent ICI-treated cohort (n = 1423). Based on multiomics data, we found that NOTCH4 mutation is significantly associated with enhanced immunogenicity, including a high tumor mutational burden, the expression of costimulatory molecules, and activation of the antigen-processing machinery, and NOTCH4 mutation positively correlates activated antitumor immunity, including infiltration of diverse immune cells and various immune marker sets. Conclusions Our findings indicated that NOTCH4 mutation serves as a novel biomarker correlated with a better response to ICI therapy.

Recurrent Sigmoid Diverticulitis After Intravesical Bacillus Calmette-Guérin (BCG) Immunotherapy for Bladder Cancer

2021 ◽  
Vol 3 (2) ◽  
pp. 580-583
Author(s):  
Ayesha Kamal ◽  
Furqan Bullar ◽  
Dilhana Badurdeen ◽  
Tinsay Woreta ◽  
Venkata S. Akshintala
Keyword(s):  
Bladder Cancer ◽  
Sigmoid Diverticulitis ◽  
Bacillus Calmette Guerin ◽  
Bcg Immunotherapy
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