Current Clinical Trials in Non-muscle Invasive Bladder Cancer

Nykopp, Timo K.; Costa, José Batista da; Mannas, Miles; Black, Peter C.

doi:10.1007/s11934-018-0852-6

Cited by 27 publications

(17 citation statements)

References 68 publications

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“…Furthermore, BC can be low grade or high grade and can also be divided into MIBC and NMIBC; low grade BC rarely invades the muscular wall of the bladder and patients rarely succumb to low grade BC, while high grade BC is more likely to result in mortality (6). Furthermore, patients with NMIBC exhibit a favorable outcome (5-year overall survival of 95 vs. 69% in MIBC) (36). However, 70% of patients with BC will experience recurrence following initial treatment (surgery, radiotherapy or chemotherapy), including 30% out of the 70% of patients presenting with muscle invasive disease (37).…”

Section: Discussionmentioning

confidence: 99%

Downregulation of ST3GAL5 is associated with muscle invasion, high grade and a poor prognosis in patients with bladder cancer

et al. 2020

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In patients with bladder cancer (BC), the association between ST3 β-galactoside α-2,3-sialyltransferase 5 (ST3GAL5) expression and clinical outcomes, particularly regarding muscle-invasive disease, high tumor grade and prognosis, remain unknown. In the present study, the expression of ST3GAL5 and its association with clinical outcomes in patients with BC was analyzed using various public bioinformatics databases. The difference in ST3GAL5 expression between BC and healthy bladder tissues was also evaluated using data from the Oncomine database, The Cancer Genome Atlas and Gene Expression Omnibus database. The differences in ST3GAL5 expression between muscle invasive BC (MIBC) and non-muscle invasive BC (NMIBC), and high-and low-grade BC were also analyzed. Furthermore, genes that were positively co-expressed with ST3GAL5 in patients with BC were identified from the intersection between the Oncomine, Gene Expression Profiling Interactive Analysis 2 and UALCAN databases. Enrichment analysis by Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, Reactome pathway enrichment analyses and a gene-concept network was performed using R package. Gene set enrichment analysis was also performed to assess the signaling pathways influenced by the high and low expression of ST3GAL5 in BC. The results indicated that ST3GAL5 expression was significantly lower in BC tissues compared with normal bladder tissues (P<0.05). Furthermore, ST3GAL5 expression in MIBC and high-grade BC was significantly lower compared with NMIBC and low-grade BC (P<0.05), respectively. The results from Kaplan-Meier survival analysis result demonstrated that ST3GAL5 downregulation was associated with poor survival in patients with BC (P<0.05). Taken together, these findings suggested that ST3GAL5 may be considered as an anti-oncogene in BC, could represent a potential predictive and prognostic biomarker for BC and may be a molecular target for tumor therapy.

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Section: Discussionmentioning

confidence: 99%

Downregulation of ST3GAL5 is associated with muscle invasion, high grade and a poor prognosis in patients with bladder cancer

et al. 2020

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“…Since the introduction of intravesical BCG therapy almost 40 years ago, the medical management of NMIBC has remained static. Multiple novel agents to be used in combination with BCG, as an alternative to BCG or after BCG failure, are being explored and show great promise . Current models fail to accurately identify patients with NMIBC who are at the highest risk of progression to muscle‐invasive and/or metastatic disease, despite adjuvant treatment with BCG immunotherapy.…”

Section: Discussionmentioning

confidence: 99%

Circulating Tumor Cells Identify Patients with Super-High-Risk Non-Muscle-Invasive Bladder Cancer: Updated Outcome Analysis of a Prospective Single-Center Trial

et al. 2019

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Background Clinical behavior of non‐muscle‐invasive bladder cancer (NMIBC) is largely unpredictable, and even patients treated according to European Association of Urology recommendations have a heterogeneous prognosis. High‐grade T1 (HGT1) bladder cancer is the highest‐risk subtype of NMIBC, with an almost 40% rate of recurrence and 20% of progression at 5 years. Nomograms predicting risk of recurrence, progression, and cancer‐specific survival (CSS) are not available specifically within HGT1 bladder cancer, and the identification of robust prognostic biomarkers to better guide therapeutic strategies in this subgroup of patients is of paramount importance. Strategies to identify putative biomarkers in liquid biopsies from blood and urine collected from patients with bladder cancer have been intensively studied in the last few years. Subjects, Materials, and Methods We here report the final analysis of a single‐center prospective study aimed to investigate the impact of circulating tumor cells (CTCs) on CSS and overall survival (OS) in 102 patients with HGT1 bladder cancer, in a median follow‐up of 63 months. Results We here demonstrate that the presence of even a single CTC is predictive of shorter CSS and OS, as compared with the standard predictive variables. Points of attention in this multivariable analysis are the long‐term follow‐up and the adequate number of outcome events. Conclusion The accurate risk stratification provided by CTCs might be essential for determining the best surveillance strategy for patients after diagnosis. A closer follow‐up, an early radical surgery, or even a systemic treatment might be recommended in patients with super‐high‐risk non‐muscle‐invasive bladder cancer. Implications for Practice Circulating tumor cells identify patients with super‐high‐risk non‐muscle‐invasive bladder cancer who require closer monitoring for local recurrence and/or progression of disease. This super‐high‐risk subgroup of patients might also require more aggressive treatment interventions, which should be evaluated in large prospective cohorts.

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“…Indeed, there are suggestions in the literature that BCG vaccination may improve the efficacy of BCG immunotherapy in bladder cancer therapy, both in experimental models and in human patients (41). A pilot study is currently ongoing to assess the effect of BCG vaccination in bladder cancer patients (42).…”

Section: Discussionmentioning

confidence: 99%

In vitro Evidence of Human Immune Responsiveness Shows the Improved Potential of a Recombinant BCG Strain for Bladder Cancer Treatment

et al. 2019

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The live attenuated mycobacterial strain BCG, in use as vaccine against tuberculosis, is considered the gold standard for primary therapy of carcinoma in situ of the bladder. Despite its limitations, to date it has not been surpassed by any other treatment. Our group has developed a recombinant BCG strain expressing the detoxified S1 pertussis toxin (rBCG-S1PT) that proved more effective than wild type BCG (WT-BCG) in increasing survival time in an experimental mouse model of bladder cancer, due to the well-known adjuvant properties of pertussis toxin. Here, we investigated the capacity of rBCG-S1PT to stimulate human immune responses, in comparison to WT-BCG, using an in vitro stimulation assay based on human whole blood cells that allows for a comprehensive evaluation of leukocyte activation. Blood leukocytes stimulated with rBCG-S1PT produced increased levels of IL-6, IL-8, and IL-10 as compared to WT-BCG, but comparable levels of IL-1β, IL-2, IFN-γ, and TNF-α. Stimulation of blood cells with the recombinant BCG strain also enhanced the expression of CD25 and CD69 on human CD4 + T cells. PBMC stimulated with rBCG-S1PT induced higher cytotoxicity to MB49 bladder cancer cells than WT-BCG-stimulated PBMC. These results suggest that the rBCG-S1PT strain is able to activate an immune response in human leukocytes that is higher than that induced by WT-BCG for parameters linked to better prognosis in bladder cancer (regulation of immune and early inflammatory responses), while fully comparable to WT-BCG for classical inflammatory parameters. This establishes rBCG-S1PT as a new highly effective candidate as immunotherapeutic agent against bladder cancer.

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Current Clinical Trials in Non-muscle Invasive Bladder Cancer

Cited by 27 publications

References 68 publications

Downregulation of ST3GAL5 is associated with muscle invasion, high grade and a poor prognosis in patients with bladder cancer

Downregulation of ST3GAL5 is associated with muscle invasion, high grade and a poor prognosis in patients with bladder cancer

Circulating Tumor Cells Identify Patients with Super-High-Risk Non-Muscle-Invasive Bladder Cancer: Updated Outcome Analysis of a Prospective Single-Center Trial

In vitro Evidence of Human Immune Responsiveness Shows the Improved Potential of a Recombinant BCG Strain for Bladder Cancer Treatment

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