scholarly journals FGFR3 – a Central Player in Bladder Cancer Pathogenesis?

2020 ◽  
Vol 6 (4) ◽  
pp. 403-423
Author(s):  
Margaret A. Knowles
Keyword(s):  
Bladder Cancer ◽  
Clinical Trials ◽  
Receptor Expression ◽  
Bladder Tumors ◽  
Cancer Pathogenesis ◽  
Early Results ◽  
Major Interest ◽  
Muscle Invasive ◽  
Mutant Forms ◽  
Normal Urothelium

The identification of mutations in FGFR3 in bladder tumors in 1999 led to major interest in this receptor and during the subsequent 20 years much has been learnt about the mutational profiles found in bladder cancer, the phenotypes associated with these and the potential of this mutated protein as a target for therapy. Based on mutational and expression data, it is estimated that >80% of non-muscle-invasive bladder cancers (NMIBC) and ∼40% of muscle-invasive bladder cancers (MIBC) have upregulated FGFR3 signalling, and these frequencies are likely to be even higher if alternative splicing of the receptor, expression of ligands and changes in regulatory mechanisms are taken into account. Major efforts by the pharmaceutical industry have led to development of a range of agents targeting FGFR3 and other FGF receptors. Several of these have entered clinical trials, and some have presented very encouraging early results in advanced bladder cancer. Recent reviews have summarised the drugs and related clinical trials in this area. This review will summarise what is known about the effects of FGFR3 and its mutant forms in normal urothelium and bladder tumors, will suggest when and how this protein contributes to urothelial cancer pathogenesis and will highlight areas that may benefit from further study.

Comparison of Thulium Laser Resection of Bladder Tumors and Conventional Transurethral Resection of Bladder Tumors for Non-Muscle-Invasive Bladder Cancer

2021 ◽  
pp. 1-6
Author(s):  
Zheng Liu ◽  
Yucong Zhang ◽  
Guoliang Sun ◽  
Wei Ouyang ◽  
Shen Wang ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Transurethral Resection ◽  
Invasive Bladder Cancer ◽  
Perioperative Outcomes ◽  
Thulium Laser ◽  
Bladder Tumors ◽  
Muscle Invasive Bladder Cancer ◽  
Laser Resection ◽  
Baseline Characteristics ◽  
Muscle Invasive

<b><i>Introduction:</i></b> The thulium laser resection of bladder tumors (TmLRBT) was increasingly used in the treatment of non-muscle-invasive bladder cancer (NMIBC) recently, and here we report the relevant outcomes of our institution to evaluate its efficacy and safety. <b><i>Methods:</i></b> We retrospectively collected the data of NMIBC patients who underwent either TmLRBT or transurethral resection of bladder tumor (TURBT). The baseline characteristics and perioperative outcomes were compared in these 2 groups. <b><i>Results:</i></b> The TmLRBT had a higher rate of detrusor identification than TURBT (97.4 vs. 87.6%, <i>p</i> = 0.001). After screening, 134 patients who underwent TmLRBT and 152 patients who received TURBT were enrolled in the analysis, and their baseline characteristics were similar. During the TURBT, 24 (15.8%) obturator nerve reflexes and 9 (5.9%) bladder perforations occurred, while none happened during the TmLRBT. After surgery, TmLRBT patients had fewer postoperative gross hematuria (38.1 vs. 96.7%, <i>p</i> &#x3c; 0.001) and postoperative irrigation (27.6 vs. 92.7%, <i>p</i> &#x3c; 0.001), and its irrigation duration was significantly shorter (2.3 vs. 3.3 day, <i>p</i> &#x3c; 0.001). During the follow-up, no significant difference in the recurrence rate was detected (<i>p</i> = 0.315). <b><i>Conclusions:</i></b> TmLRBT is a safer technique than conventional TURBT in the treatment of NMIBC, and it could offer better specimens for pathologic assessment while the cancer control was not compromised.

scholarly journals Neoadjuvant Immunotherapy for Muscle-Invasive Bladder Cancer

Medicina ◽  
2021 ◽  
Vol 57 (8) ◽  
pp. 769
Author(s):  
Arthur Peyrottes ◽  
Idir Ouzaid ◽  
Gianluigi Califano ◽  
Jean-Francois Hermieu ◽  
Evanguelos Xylinas
Keyword(s):  
Bladder Cancer ◽  
Clinical Trials ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Response Rate ◽  
Checkpoint Inhibitor ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Neoadjuvant Immunotherapy ◽  
Muscle Invasive

Background and Objectives: Facing neoadjuvant chemotherapy followed by surgery, neoadjuvant immunotherapy is an innovative concept in localized muscle-invasive bladder cancer. Herein, we performed a review of the available and ongoing evidence supporting immune checkpoint inhibitor (ICI) administration in the early stages of bladder cancer treatment. Materials and Methods: A literature search was performed on Medline and clinical trials databases, using the terms: “bladder cancer” OR “urothelial carcinoma”, AND “neoadjuvant immunotherapy” OR “preoperative immunotherapy”. We restricted our investigations to prospective clinical trials evaluating anti-PD-(L)1 and anti-CTLA-4 monoclonal antibodies. Data on efficacy, toxicity and potential biomarkers of response were retrieved. Results: The search identified 6 ICIs that were tested in the neoadjuvant setting for localized bladder cancer—4 anti-PD-(L)1 inhibitors (Pembrolizumab, Atezolizumab, Nivolumab and Durvalumab) and 2 anti-CTLA-4 inhibitors (Ipilimumab and Tremelimumab). Most of the existing literature was based on single-arm phase 2 clinical trials that included from 23 to 143 patients. The pathological complete response rate (pCR) and pathological response rate (pRR) ranged from 31% to 46% and from 55.9% to 66%, respectively. Survival data were immature at this time. The safety profile was acceptable, with severe treatment-related adverse events ranging from 6% to 41%. Conclusions: The results of early phase trials are encouraging, and more investigations are needed to strengthen the rationale for immune checkpoint inhibitor administration in localized muscle-invasive bladder cancer.

scholarly journals Biomarkers in Bladder Cancer Surveillance

2021 ◽  
Vol 8 ◽  
Author(s):  
Sukumar S. Sugeeta ◽  
Anand Sharma ◽  
Kenrick Ng ◽  
Arvind Nayak ◽  
Nikhil Vasdev
Keyword(s):  
Bladder Cancer ◽  
Clinical Trials ◽  
Prospective Studies ◽  
Urine Cytology ◽  
Cancer Surveillance ◽  
Invasive Bladder Cancer ◽  
Low Grade ◽  
Protein Biomarkers ◽  
Muscle Invasive Bladder Cancer ◽  
Muscle Invasive

Aim: This is a narrative review with an aim to summarise and describe urinary biomarkers in the surveillance of non-muscle-invasive bladder cancer (NMIBC). It provides a summary of FDA-approved protein biomarkers along with emerging ones which utilise genetic, epigenetic and exosomal markers. We discuss the current limitations of the available assays.Background: Current guidelines advice a combination of cystoscopy, imaging,and urine cytology in diagnosis and surveillance. Although cytology has a high specificity, it is limited by low sensitivity particularly in low grade tumours. There are six FDA-approved urinary assays for diagnosis and surveillance of bladder cancer. They have shown to improve sensitivity and specificity to be used alongside cytology and cystoscopy but have a lower specificity in comparison to cytology and false positives often occur in benign conditions. Recent developments in laboratory techniques has allowed for use of markers which are RNA-, DNA-based as well as extracellular vesicles in the past decade.Methods: Using the PubMed/Medline search engines as well as Google Scholar, we performed an online search using the terms “bladder cancer,” “non-muscle invasive bladder cancer,” and “urine biomarkers” with filter for articles in English published up to May 2021. Systematic reviews and original data of clinical trials or observational studies which contributed to the development of the biomarkers were collated.Results: Biomarkers identified were divided into FDA-approved molecular biomarkers, protein biomarkers and gene-related biomarker with a table summarising the findings of each marker with the most relevant studies. The studies conducted were mainly retrospective. Due to the early stages of development, only a few prospective studies have been done for more recently developed biomarkers and limited meta-analyses are available.Therefore a detailed evaluation of these markers are still required to decide on their clinical use.Conclusion: Advancements of analytical methods in BC has driven the research towards non-invasive liquid-based biomarkers in adjunct to urine cytology. Further large prospective studies are required to determine its feasibility in a clinical setting as they are not effective when used in isolation as they have their limitation. With the ongoing pandemic, other than reduction in costs and increased accuracy, the need for biomarkers to cope with delay in cystoscopies in diagnosis and surveillance is crucial. Thus clinical trials with direct comparison is required to improve patient care.

How well do we manage non-muscle invasive bladder tumors? A UK audit of real-life practices

2020 ◽  
Vol 87 (3) ◽  
pp. 142-148
Author(s):  
Petros Sountoulides ◽  
Wilbert Fana Mutomba ◽  
Emmanouil Bouras ◽  
Jieqi Lim ◽  
Andreas Bourdoumis ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Carcinoma In Situ ◽  
Real Life ◽  
Invasive Bladder Cancer ◽  
Detrusor Muscle ◽  
Bladder Tumors ◽  
Recurrence Rates ◽  
Muscle Invasive Bladder Cancer ◽  
Muscle Invasive

Objective: The aim of this study was to assess the quality of TURBT (transurethral resection of bladder tumor) using surrogate parameters and evaluate adherence to the guidelines regarding the management of bladder tumors. Materials and methods: A clinical audit of all new diagnosis of bladder cancer was undertaken from January 2016 to January 2017. A total of 101 new bladder cancer cases were included. Surrogates of TURBT quality including presence of detrusor in the specimen, rate of re-TUR, presence of carcinoma in situ, and 3-month recurrence rates were analyzed. Adherence to guidelines regarding management of non-muscle invasive bladder cancer including time to re-TUR and utilization of single instillation chemotherapy was evaluated. Results: Absence of detrusor muscle in the specimen of the initial TURBT was noted in 22.8% of the cases. The chance of including muscle in the specimen was almost four-fold for tumors larger than 3 cm. A single instillation of intravesical chemotherapy following TURBT was administered in only 40% of eligible patients; 54.3% of patients had a re-TUR, the majority (61.3%) for high-grade non-muscle invasive bladder cancer on initial TURBT. Re-TUR was done on average 10 weeks after initial TURBT. The 3-month recurrence rate was 36.0% with larger tumors (>3 cm) being more prone to early recurrences. Early recurrences were not affected by intravesical instillations with bacillus Calmette–Guérin or mitomycin C although there was a positive association between the presence of carcinoma in situ on initial resection and early recurrences. Discussion and conclusion: One in two patients will have a re-TUR, and approximately one in two patients will have tumor on re-TUR. Single immediate chemotherapy instillations after TURBT are underutilized. The presence of carcinoma in situ on initial TURBT and tumor size were predictors of early recurrences.

Defining Molecular Profiles of Poor Outcome in Patients With Invasive Bladder Cancer Using Oligonucleotide Microarrays

2006 ◽  
Vol 24 (5) ◽  
pp. 778-789 ◽  
Author(s):  
Marta Sanchez-Carbayo ◽  
Nicholas D. Socci ◽  
Juanjo Lozano ◽  
Fabien Saint ◽  
Carlos Cordon-Cardo
Keyword(s):  
Overall Survival ◽  
Bladder Cancer ◽  
Clinical Outcome ◽  
Tumor Staging ◽  
Invasive Disease ◽  
Bladder Tumors ◽  
Tissue Arrays ◽  
Node Metastases ◽  
Normal Urothelium ◽  
Immunohistochemical Analyses

Purpose Bladder cancer is a common malignancy characterized by a poor clinical outcome when tumors progress into invasive disease. We sought to define genetic signatures characteristic of aggressive clinical behavior in advanced bladder tumors. Methods Oligonucleotide arrays were utilized to analyze the transcript profiles of 105 bladder tumors: 33 superficial, 72 invasive lesions, and 52 normal urothelium. Hierarchical clustering and supervised algorithms were used to classify and stratify bladder tumors on the basis of stage, node metastases, and overall survival. Immunohistochemical analyses on bladder cancer tissue arrays (n = 294 cases) served to validate associations between marker expression, staging and outcome. Results Hierarchical clustering classified normal urothelium, superficial, and invasive tumors with 82.2% accuracy, and stratified bladder tumors on the basis of clinical outcome. Predictive algorithms rendered an 89%-correct rate for tumor staging using genes differentially expressed between superficial and invasive tumors. Accuracies of 82% and 90% were obtained for predicting overall survival when considering all patients with bladder cancer or only patients with invasive disease, respectively. A genetic profile consisting of 174 probes was identified in those patients with positive lymph nodes and poor survival. Two independent Global Test runs confirmed the robust association of this profile with lymph node metastases (P = 7.3–13) and overall survival (P = 1.9–14) simultaneously. Immunohistochemical analyses on tissue arrays sustained the significant association of synuclein with tumor staging and clinical outcome (P = .002). Conclusion Gene profiling provides a genomic-based classification scheme of diagnostic and prognostic utility for stratifying advanced bladder cancer. Identification of this poor outcome profile could assist in selecting patients who may benefit from more aggressive therapeutic intervention.

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