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Nature Reviews. Disease Primers Oct 2023Bladder cancer is a global health issue with sex differences in incidence and prognosis. Bladder cancer has distinct molecular subtypes with multiple pathogenic pathways... (Review)
Review
Bladder cancer is a global health issue with sex differences in incidence and prognosis. Bladder cancer has distinct molecular subtypes with multiple pathogenic pathways depending on whether the disease is non-muscle invasive or muscle invasive. The mutational burden is higher in muscle-invasive than in non-muscle-invasive disease. Commonly mutated genes include TERT, FGFR3, TP53, PIK3CA, STAG2 and genes involved in chromatin modification. Subtyping of both forms of bladder cancer is likely to change considerably with the advent of single-cell analysis methods. Early detection signifies a better disease prognosis; thus, minimally invasive diagnostic options are needed to improve patient outcomes. Urine-based tests are available for disease diagnosis and surveillance, and analysis of blood-based cell-free DNA is a promising tool for the detection of minimal residual disease and metastatic relapse. Transurethral resection is the cornerstone treatment for non-muscle-invasive bladder cancer and intravesical therapy can further improve oncological outcomes. For muscle-invasive bladder cancer, radical cystectomy with neoadjuvant chemotherapy is the standard of care with evidence supporting trimodality therapy. Immune-checkpoint inhibitors have demonstrated benefit in non-muscle-invasive, muscle-invasive and metastatic bladder cancer. Effective management requires a multidisciplinary approach that considers patient characteristics and molecular disease characteristics.
Topics: Humans; Female; Male; Treatment Outcome; Neoplasm Recurrence, Local; Urinary Bladder Neoplasms; Urinary Bladder; Prognosis
PubMed: 37884563
DOI: 10.1038/s41572-023-00468-9 -
Medicina (Kaunas, Lithuania) Jul 2021Bladder cancer (BCa) is the most common malignancy of the urinary tract and one of the most prevalent cancers worldwide. While the clinical approach to BCa has remained... (Review)
Review
Bladder cancer (BCa) is the most common malignancy of the urinary tract and one of the most prevalent cancers worldwide. While the clinical approach to BCa has remained largely unchanged for many years, recent discoveries have paved the way to a new era of diagnosis and management of the disease. BCa-specific mortality started to decrease in the regions with a wide range of activities leading to greater social awareness of the risk factors and the decline in carcinogenic exposure. The urologic community refines the role of transurethral surgery towards more rigorous and high-quality techniques. New agents have been approved for patients with BCG failure who faced radical cystectomy so far. Although radical removal of the bladder is the gold standard for muscle invasive cancer management, the extent and clinical value of lymphadenectomy is currently heavily challenged in randomized trials. Furthermore, alternatives to perioperative chemotherapy have arisen to increase the likelihood of complete treatment delivery and successful oncological outcomes. Finally, improvements in molecular biology and our understanding of tumorigenesis open the era of personalized medicine in bladder cancer. In the present review, the status and future directions in bladder cancer epidemiology, diagnosis and management are thoroughly discussed.
Topics: Cystectomy; Humans; Lymph Node Excision; Neoplasm Invasiveness; Risk Factors; Urinary Bladder Neoplasms
PubMed: 34440955
DOI: 10.3390/medicina57080749 -
BJU International Mar 2017Non-muscle-invasive bladder cancer (NMIBC) represents the vast majority of bladder cancer diagnoses, but this definition represents a spectrum of disease with a variable... (Review)
Review
Non-muscle-invasive bladder cancer (NMIBC) represents the vast majority of bladder cancer diagnoses, but this definition represents a spectrum of disease with a variable clinical course, notable for significant risk of recurrence and potential for progression. Management involves risk-adapted strategies of cystoscopic surveillance and intravesical therapy with the goal of bladder preservation when safe to do so. Multiple organizational guidelines exist to help practitioners manage this complicated disease process, but adherence to management principles among practising urologists is reportedly low. We review four major organizational guidelines on NMIBC: the American Urological Association (AUA)/Society of Urologic Oncology (SUO), European Association of Urology (EAU), National Comprehensive Cancer Network (NCCN), and National Institute for Health and Care Excellence (NICE) guidelines.
Topics: Humans; Muscle, Smooth; Neoplasm Invasiveness; Practice Guidelines as Topic; Urinary Bladder Neoplasms
PubMed: 28058776
DOI: 10.1111/bju.13760 -
Drugs Mar 2023Nadofaragene firadenovec (nadofaragene firadenovec-vncg; Adstiladrin) is a non-replicating adenoviral vector-based gene therapy developed by Ferring Pharmaceuticals for... (Review)
Review
Nadofaragene firadenovec (nadofaragene firadenovec-vncg; Adstiladrin) is a non-replicating adenoviral vector-based gene therapy developed by Ferring Pharmaceuticals for the treatment of high-risk Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle invasive bladder cancer (NMIBC). Nadofaragene firadenovec constitutes vector DNA that encodes for interferon (IFN)-α2b and is the first approved gene therapy in bladder cancer. The production of IFN-α2b by transfected urothelial cells is associated with anticancer activity, including immunostimulatory, antiangiogenic and apoptotic effects. In December 2022, nadofaragene firadenovec received its first global approval in the USA for the treatment of high-risk BCG-unresponsive NMIBC with carcinoma in situ (CIS) with or without papillary tumours in adults. This article summarizes the milestones in the development of nadofaragene firadenovec leading to this first approval for this indication.
Topics: Adult; Humans; BCG Vaccine; Adjuvants, Immunologic; Administration, Intravesical; Antineoplastic Agents; Urinary Bladder Neoplasms; Interferon-alpha; Neoplasm Invasiveness; Neoplasm Recurrence, Local
PubMed: 36856952
DOI: 10.1007/s40265-023-01846-z -
International Braz J Urol : Official... 2020Standard management of muscle-invasive bladder cancer involves radical cystectomy with pelvic lymph node dissection. However, patients may be ineligible for surgery or... (Review)
Review
BACKGROUND
Standard management of muscle-invasive bladder cancer involves radical cystectomy with pelvic lymph node dissection. However, patients may be ineligible for surgery or may wish to avoid the morbidity of cystectomy due to quality of life concerns. Bladder preservation therapies have emerged as alternatives treatment options that can provide comparable oncologic outcomes while maintaining patients' quality of life.
OBJECTIVE
To review bladder preservation therapies, patient selection criteria, and functional and oncologic outcomes for BPT in muscle-invasive bladder cancer.
MATERIALS AND METHODS
We conducted a comprehensive literature review of bladder preservation therapies in Pubmed and Embase.
DISCUSSION
The ideal patient for BPT has low-volume T2 disease, absence of CIS, absence of hydronephrosis, and a maximal TURBT with regular surveillance. Technological advancements involving cancer staging, TURBT technique, and chemotherapy and radiation therapy regimens have improved BPT outcomes, with oncologic outcomes now comparable to those of radical cystectomy. Advancements in BPT also includes a heightened focus on improving quality of life for patients undergoing bladder preservation. Preservation strategies with most evidence for use include trimodality therapy and partial cystectomy with pelvic lymph node dissection.
CONCLUSIONS
This review highlights the breadth of strategies that aim to preserve a patient's bladder while still optimizing local tumor control and overall survival. Future areas for innovation include the use of predictive biomarkers and implementation of immunotherapy, moving the field towards patient-tailored care.
Topics: Combined Modality Therapy; Cystectomy; Humans; Neoplasm Invasiveness; Neoplasm Staging; Organ Sparing Treatments; Urinary Bladder Neoplasms
PubMed: 31961624
DOI: 10.1590/S1677-5538.IBJU.2020.99.01 -
Cancer Cell May 2021Discovery-driven research and clinical research have worked together to change the outcomes of many cancer patients. We choose urothelial carcinoma as an example to... (Review)
Review
Discovery-driven research and clinical research have worked together to change the outcomes of many cancer patients. We choose urothelial carcinoma as an example to showcase how recent diagnostic and therapeutic innovations have re-shaped cancer clinical practice.
Topics: Carcinoma, Transitional Cell; Humans; Neoplasm Metastasis; Research; Urinary Bladder Neoplasms
PubMed: 33974855
DOI: 10.1016/j.ccell.2021.04.012 -
The Journal of Urology Sep 2017This multidisciplinary, evidence-based guideline for clinically non-metastatic muscle-invasive bladder cancer focuses on the evaluation, treatment and surveillance of...
PURPOSE
This multidisciplinary, evidence-based guideline for clinically non-metastatic muscle-invasive bladder cancer focuses on the evaluation, treatment and surveillance of muscle-invasive bladder cancer guided toward curative intent.
MATERIALS AND METHODS
A systematic review utilizing research from the Agency for Healthcare Research and Quality as well as additional supplementation by the authors and consultant methodologists was used to develop the guideline. Evidence-based statements were based on body of evidence strengths Grade A, B or C and were designated as Strong, Moderate and Conditional Recommendations with additional statements presented in the form of Clinical Principles or Expert Opinions.
RESULTS
For the first time for any type of malignancy, the American Urological Association, American Society of Clinical Oncology, American Society for Radiation Oncology and Society of Urologic Oncology have formulated an evidence-based guideline based on a risk-stratified clinical framework for the management of muscle-invasive urothelial bladder cancer. This document is designed to be used in conjunction with the associated treatment algorithm.
CONCLUSIONS
The intensity and scope of care for muscle-invasive bladder cancer should focus on the patient, disease and treatment response characteristics. This guideline attempts to improve a clinician's ability to evaluate and treat each patient, but higher quality evidence in future trials will be essential to improve level of care for these patients.
Topics: Algorithms; Antineoplastic Agents; Combined Modality Therapy; Cystectomy; Humans; Neoplasm Invasiveness; Neoplasm Staging; Urinary Bladder Neoplasms; Watchful Waiting
PubMed: 28456635
DOI: 10.1016/j.juro.2017.04.086 -
Lipids in Health and Disease Oct 2021Bladder cancer (BLCA) is a common cancer associated with an unfavorable prognosis. Increasing numbers of studies have demonstrated that lipid metabolism affects the...
BACKGROUND
Bladder cancer (BLCA) is a common cancer associated with an unfavorable prognosis. Increasing numbers of studies have demonstrated that lipid metabolism affects the progression and treatment of tumors. Therefore, this study aimed to explore the function and prognostic value of lipid metabolism-related genes in patients with bladder cancer.
METHODS
Lipid metabolism-related genes (LRGs) were acquired from the Molecular Signature Database (MSigDB). LRG mRNA expression and patient clinical data were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets. Cox regression analysis and least absolute shrinkage and selection operator (LASSO) regression analysis was used to construct a signature for predicting overall survival of patients with BLCA. Kaplan-Meier analysis was performed to assess prognosis. The connectivity Map (CMAP) database was used to identify small molecule drugs for treatment. A nomogram was constructed and assessed by combining the signature and other clinical factors. The CIBERSORT, MCPcounter, QUANTISEQ, XCELL, CIBERSORT-ABS, TIMER and EPIC algorithms were used to analyze the immunological characteristics.
RESULTS
An 11-LRG signature was successfully constructed and validated to predict the prognosis of BLCA patients. Furthermore, we also found that the 11-gene signature was an independent hazardous factor. Functional analysis suggested that the LRGs were closely related to the PPAR signaling pathway, fatty acid metabolism and AMPK signaling pathway. The prognostic model was closely related to immune cell infiltration. Moreover, the expression of key immune checkpoint genes (PD1, CTLA4, PD-L1, LAG3, and HAVCR2) was higher in patients in the high-risk group than in those in the low-risk group. The prognostic signature based on 11-LRGs exhibited better performance in predicting overall survival than conventional clinical characteristics. Five small molecule drugs could be candidate drug treatments for BLCA patients based on the CMAP dataset.
CONCLUSIONS
In conclusion, the current study identified a reliable signature based on 11-LRGs for predicting the prognosis and response to immunotherapy in patients with BLCA. Five small molecule drugs were identified for the treatments of BLCA patients.
Topics: Aged; Antineoplastic Agents; Female; Genes, Neoplasm; Humans; Kaplan-Meier Estimate; Lipid Metabolism; Male; Middle Aged; Prognosis; Proportional Hazards Models; Reproducibility of Results; Survival Analysis; Urinary Bladder Neoplasms
PubMed: 34706720
DOI: 10.1186/s12944-021-01554-1 -
Investigative and Clinical Urology Jun 2016The incidence of urothelial carcinoma of the urinary bladder (bladder cancer) remains high. While other solid organ malignancies have seen significant improvement in... (Review)
Review
The incidence of urothelial carcinoma of the urinary bladder (bladder cancer) remains high. While other solid organ malignancies have seen significant improvement in morbidity and mortality, there has been little change in bladder cancer mortality in the past few decades. The mortality is mainly driven by muscle invasive bladder cancer, but the cancer burden remains high even in nonmuscle invasive bladder cancer due to high recurrence rates and risk of progression. While apoptosis deregulation has long been an established pathway for cancer progression, nonapoptotic pathways have gained prominence of late. Recent research in the role of autophagy in other malignancies, including its role in treatment resistance, has led to greater interest in the role of autophagy in bladder cancer. Herein, we summarize the literature regarding the role of autophagy in bladder cancer progression and treatment resistance. We address it by systematically reviewing treatment modalities for nonmuscle invasive and muscle invasive bladder cancer.
Topics: Antineoplastic Agents; Autophagy; Carcinoma, Transitional Cell; Disease Progression; Drug Resistance, Neoplasm; Humans; Neoplasm Invasiveness; Urinary Bladder Neoplasms
PubMed: 27326411
DOI: 10.4111/icu.2016.57.S1.S89 -
International Journal of Molecular... Jul 2023Multiple risk factors have been associated with bladder cancer. This review focuses on pesticide exposure, as it is not currently known whether agricultural products... (Review)
Review
Multiple risk factors have been associated with bladder cancer. This review focuses on pesticide exposure, as it is not currently known whether agricultural products have a direct or indirect effect on bladder cancer, despite recent reports demonstrating a strong correlation. While it is known that pesticide exposure is associated with an increased risk of bladder cancer in humans and dogs, the mechanism(s) by which specific pesticides cause bladder cancer initiation or progression is unknown. In this narrative review, we discuss what is currently known about pesticide exposure and the link to bladder cancer. This review highlights multiple pathways modulated by pesticide exposure with direct links to bladder cancer oncogenesis/metastasis (MMP-2, TGF-β, STAT3) and chemoresistance (drug efflux, DNA repair, and apoptosis resistance) and potential therapeutic tactics to counter these pesticide-induced affects.
Topics: Humans; Animals; Dogs; Pesticides; Drug Resistance, Neoplasm; Urinary Bladder Neoplasms; Risk Factors; Antineoplastic Agents
PubMed: 37511154
DOI: 10.3390/ijms241411395