EAU Guidelines on Non–Muscle-invasive Urothelial Carcinoma of the Bladder: Update 2016

Babjuk, Marko; Böhle, Andreas; Burger, Maximilian; Čapoun, Otakar; Cohen, Daniel L.; Compérat, Éva; Hernández, Virginia; Kaasinen, Eero; Palou, Joan; Rouprêt, Morgan; Rhijn, Bas W.G. van; Shariat, Shahrokh F.; Soukup, Viktor; Sylvester, Richard; Zigeuner, Richard

doi:10.1016/j.eururo.2016.05.041

Cited by 1,695 publications

(1,476 citation statements)

References 123 publications

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“…Thirty-to-forty percent of high risk of progression NMBIC patients, particularly those presenting with carcinoma in situ lesions, will not respond to BCG therapy and would thus greatly benefit from a more efficient drug, that could avoid radical cystectomy. 26 Altogether, our preclinical data demonstrate that intravesical Ty21a is more effective than BCG for bladder-tumor treatment. Absence of surviving Ty21a bacteria and the excellent safety-record of the typhoid vaccine support its further testing for intravesical immunotherapy of NMIBC patients.…”

Section: D-bladder Assay Il-6 Il-8 Il-12 Gm-csf Mcp-1 and Vegfmentioning

confidence: 79%

Preclinical efficacy and safety of the Ty21a vaccine strain for intravesical immunotherapy of non-muscle-invasive bladder cancer

et al. 2016

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Intravesical Bacillus-Calmette-Guerin (BCG) immunotherapy can reduce recurrence/progression of nonmuscle-invasive bladder cancer (NMIBC), although significant adverse events and treatment failure argue for alternative options. Here, we examined whether another attenuated live vaccine, Vivotif/Ty21a, used since more than 30 y against typhoid fever, may be safely used intravesically to improve bladder-tumor treatment. Mice-bearing MB49 orthotopic bladder-tumors treated with intravesical Ty21a or BCG were compared for survival and bacteria recovery. Both Ty21a and BCG enhanced mice survival when treating just after tumor implantation for 4 weeks (p D 0.008 and 0.04, respectively), but only Ty21a was effective when treating once mice with larger already established bladder-tumors (p D 0.0003). In contrast to BCG, no Ty21a bacteria survived in mouse bladder, human urothelial cell-lines or human peripheral blood mononuclear cells. However, Ty21a was as potent as BCG to induce tumor-cell death in vitro. In a human, 3D-bladder-tissue ex-vivo assay, Ty21a bacteria, still not surviving, induced a panel of cytokines associated with effective BCG-treatment in patient's urine. Overall, our pre-clinical data demonstrate that intravesical Ty21a is more effective than BCG for bladder-tumor treatment. Absence of surviving Ty21a bacteria and the excellent safety-record of the typhoid vaccine support its testing in NMIBC patients.

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Section: D-bladder Assay Il-6 Il-8 Il-12 Gm-csf Mcp-1 and Vegfmentioning

confidence: 79%

Preclinical efficacy and safety of the Ty21a vaccine strain for intravesical immunotherapy of non-muscle-invasive bladder cancer

et al. 2016

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“…Despite the continuous development of medical techniques, the diagnostics, treatments, and survivals for bladder cancer have been largely unchanged since the 1990s 3. Although NMIBC patients with a better prognosis than MIBC, and even through tumors can be successfully identified and removed before they become invasive, BC has a high rate of recurrence and progression 4. Cystoscopies are the gold standard for diagnosis of BC, but they are expensive and uncomfortable 5.…”

Section: Introductionmentioning

confidence: 99%

CD164 promotes tumor progression and predicts the poor prognosis of bladder cancer

Zhang

Li³

et al. 2018

Cancer Medicine

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CD164 was found to play a role in many malignant diseases. But the roles of CD164 in human bladder cancer have not yet been studied. The object of our study was to investigate the functions of CD164 in urothelial bladder carcinoma. The immunohistochemistry (IHC) was performed to evaluate the associations between the expression level of CD164 and clinical‐pathological features of patients, and IHC was used to analyze the relationship between CD164 and CXCR4 in tumor tissues. Real‐time qPCR and Western blot were used to measure the expression of relevant genes. The roles of CD164 in tumor cells and tissues were investigated by in vitro and in vivo experiments. The results of immunohistochemistry found that CD164 was associated with clinical and pathological features of patients. High level of CD164 was related to the distant metastasis and vascular invasion of bladder cancer patients. In vitro, by silencing of CD164, the proliferation, migration, and invasion of tumor cells were inhibited significantly by regulating related proteins such as Ki67, proliferating cell nuclear antigen, matrix metalloproteinases‐2, and matrix metalloproteinases‐9. In vivo, knocking‐down of CD164 could reduce the growth and metastasis of tumors in mice. In addition, a co‐expression was found between CD164 and CXCR4 in tumor tissues. In conclusion, our study demonstrated that CD164 was associated with the poor clinical outcomes of BC patients. Silencing of CD164 could inhibit the progression of tumors in vivo and in vitro, which may become an effective target in the treatment of bladder cancer.

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“…Multivariate analysis abilities of conventional markers such as tumor grade or stage (2,5), the identification of reliable genetic markers predicting disease progression in NMIBC is urgently required. Previous reports demonstrated the association between CNVs and the risk of several human malignancies (11)(12)(13)(14)(15)(16).…”

Section: Univariate Analysismentioning

confidence: 99%

“…Conventional clinicopathological factors predicting disease progression include number of tumors, tumor diameter, stage, concomitant carcinoma in situ and tumor grade (2). However, the prediction of progression remains difficult based on conventional parameters, and to date, no useful biomarkers have been established for follow-up in routine practice (5).…”

Section: Introductionmentioning

confidence: 99%

Germline DNA copy number variations as potential prognostic markers for non-muscle invasive bladder cancer progression

et al. 2017

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Abstract. Accumulating evidence has suggested that germline DNA copy number variations (CNVs) affect various disorders, including human malignancies. However, the significance of CNVs in non-muscle invasive bladder cancer (NMIBC) remains unclear. The purpose of the present study was to identify the role of CNVs in NMIBC. Array comparative genomic hybridization (CGH) analysis was performed to search for candidate CNVs associated with NMIBC susceptibility. Quantitative polymerase chain reaction was carried out to evaluate CNVs associated with patient outcome in 189 NMIBC cases. In total, 11 CNVs were associated with NMIBC risk in array CGH analysis. Out of the 189 CNVs examined, family with sequence similarity 81 member A (FAM81A) and proprotein convertase subtilisin/kexin type 6 (PCSK6) CNVs exhibited a significant association with recurrence and disease progression in NMIBC. PCSK6 has been reported to regulate proliferation and tumor progression in breast and prostate malignancies. Notably, patients with pT1 stage had significantly lower PCSK6 relative copy number than those with pTa (P=0.0196). In multivariate analyses, PCSK6 copy number was an independent prognostic factor for progression-free survival (P=0.0456; risk ratio, 2.17; 95% confidence interval, 1.02-4.82). These data suggest that PCSK6 CNV is a potential new tumor marker for estimating disease progression in NMIBC.

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EAU Guidelines on Non–Muscle-invasive Urothelial Carcinoma of the Bladder: Update 2016

Cited by 1,695 publications

References 123 publications

Preclinical efficacy and safety of the Ty21a vaccine strain for intravesical immunotherapy of non-muscle-invasive bladder cancer

Preclinical efficacy and safety of the Ty21a vaccine strain for intravesical immunotherapy of non-muscle-invasive bladder cancer

CD164 promotes tumor progression and predicts the poor prognosis of bladder cancer

Germline DNA copy number variations as potential prognostic markers for non-muscle invasive bladder cancer progression

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