-
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 -
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 -
CA: a Cancer Journal For Clinicians Sep 2020Bladder cancer accounts for nearly 170,000 deaths worldwide annually. For over 4 decades, the systemic management of muscle-invasive and advanced bladder cancer has... (Review)
Review
Bladder cancer accounts for nearly 170,000 deaths worldwide annually. For over 4 decades, the systemic management of muscle-invasive and advanced bladder cancer has primarily consisted of platinum-based chemotherapy. Over the past 10 years, innovations in sequencing technologies have led to rapid genomic characterization of bladder cancer, deepening our understanding of bladder cancer pathogenesis and exposing potential therapeutic vulnerabilities. On the basis of its high mutational burden, immune checkpoint inhibitors were investigated in advanced bladder cancer, revealing durable responses in a subset of patients. These agents are now approved for several indications and highlight the changing treatment landscape of advanced bladder cancer. In addition, commonly expressed molecular targets were leveraged to develop targeted therapies, such as fibroblast growth factor receptor inhibitors and antibody-drug conjugates. The molecular characterization of bladder cancer and the development of novel therapies also have stimulated investigations into optimizing treatment approaches for muscle-invasive bladder cancer. Herein, the authors review the history of muscle-invasive and advanced bladder cancer management, highlight the important molecular characteristics of bladder cancer, describe the major advances in treatment, and offer future directions for therapeutic development.
Topics: Angiogenesis Inhibitors; Antineoplastic Agents; Biomarkers; Clinical Trials as Topic; Combined Modality Therapy; Cystectomy; Humans; Immune Checkpoint Inhibitors; Muscle, Smooth; Neoplasm Invasiveness; Organ Sparing Treatments; Receptors, Fibroblast Growth Factor; Urinary Bladder Neoplasms
PubMed: 32767764
DOI: 10.3322/caac.21631 -
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 -
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 -
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 Journal of Cancer Dec 2021Bladder cancer represents a highly heterogeneous disease characterized by distinct histological, molecular and clinical phenotypes, and a detailed analysis of tumor cell... (Observational Study)
Observational Study
Bladder cancer represents a highly heterogeneous disease characterized by distinct histological, molecular and clinical phenotypes, and a detailed analysis of tumor cell invasion and crosstalks within bladder tumor cells has not been determined. Here, we applied droplet-based single-cell RNA sequencing (scRNA-seq) to acquire transcriptional profiles of 36 619 single cells isolated from seven patients. Single cell transcriptional profiles matched well with the pathological basal/luminal subtypes. Notably, in T1 tumors diagnosed as luminal subtype, basal cells displayed characteristics of epithelial-mesenchymal transition (EMT) and mainly located at the tumor-stromal interface as well as micrometastases in the lamina propria. In one T3 tumor, muscle-invasive tumor showed significantly higher expression of cancer stem cell markers SOX9 and SOX2 than the primary tumor. We additionally analyzed communications between tumor cells and demonstrated its relevance to basal/luminal phenotypes. Overall, our single-cell study provides a deeper insight into the tumor cell heterogeneity associated with bladder cancer progression.
Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Disease Progression; Epithelial Cells; Epithelial-Mesenchymal Transition; Gene Expression Regulation, Neoplastic; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Muscle, Smooth; Neoplasm Invasiveness; RNA-Seq; Single-Cell Analysis; Tomography, X-Ray Computed; Urinary Bladder; Urinary Bladder Neoplasms
PubMed: 34480339
DOI: 10.1002/ijc.33794 -
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 -
Journal of Clinical Oncology : Official... Jan 2019Fluorouracil plus cisplatin and radiation twice a day (FCT) is an established chemoradiation (CRT) regimen for selective bladder-sparing treatment of muscle-invasive... (Randomized Controlled Trial)
Randomized Controlled Trial
Bladder Preservation With Twice-a-Day Radiation Plus Fluorouracil/Cisplatin or Once Daily Radiation Plus Gemcitabine for Muscle-Invasive Bladder Cancer: NRG/RTOG 0712-A Randomized Phase II Trial.
PURPOSE
Fluorouracil plus cisplatin and radiation twice a day (FCT) is an established chemoradiation (CRT) regimen for selective bladder-sparing treatment of muscle-invasive bladder cancer. Gemcitabine and once daily radiation (GD) is a well-supported alternative. The current trial evaluates these regimens.
METHODS
Patients with cT2-4a muscle-invasive bladder cancer were randomly assigned to FCT or GD. Patients underwent transurethral resection and induction CRT to 40 Gy. Patients who achieved a complete response (CR) received consolidation CRT to 64 Gy and others underwent cystectomy. We administered adjuvant gemcitabine/cisplatin chemotherapy. The primary end point was the rate of freedom from distant metastasis at 3 years (DMF3). The trial was not statistically powered to compare regimens, but to assess whether either regimen exceeded a DMF3 benchmark of 75%. Toxicity and efficacy end points, including CR and bladder-intact distant metastasis free survival at 3 years (BI-DMFS3), were assessed.
RESULTS
From December 2008 to April 2014, 70 patients were enrolled, of which 66 were eligible for analysis, 33 per arm. Median follow-up was 5.1 years (range, 0.4 to 7.8 years) for eligible living patients. DMF3 was 78% and 84% for FCT and GD, respectively. BI-DMFS3 was 67% and 72%, respectively. Postinduction CR rates were 88% and 78%, respectively. Of 33 patients in the FCT arm, 21 (64%) experienced treatment-related grade 3 and 4 toxicities during protocol treatment, with 18 (55%), two (6%), and two patients (6%) experiencing grade 3 and 4 hematologic, GI, and genitourinary toxicity, respectively. For the 33 patients in the GD arm, these figures were 18 (55%) overall and 14 (42%), three (9%) and two patients (6%), respectively.
CONCLUSION
Both regimens demonstrated DMF3 greater than 75%. There were fewer toxicities observed in the GD arm. Either gemcitabine and once daily radiation or a cisplatin-based regimen could serve as a base for future trials of systemic therapy.
Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy; Chemotherapy, Adjuvant; Cisplatin; Cytoreduction Surgical Procedures; Deoxycytidine; Female; Fluorouracil; Humans; Male; Middle Aged; Neoplasm Invasiveness; Neoplasm Staging; Urinary Bladder Neoplasms; Urologic Surgical Procedures; Gemcitabine
PubMed: 30433852
DOI: 10.1200/JCO.18.00537 -
The Journal of Clinical Investigation Dec 2020BACKGROUNDCurrent methods for the detection and surveillance of bladder cancer (BCa) are often invasive and/or possess suboptimal sensitivity and specificity, especially... (Clinical Trial)
Clinical Trial
BACKGROUNDCurrent methods for the detection and surveillance of bladder cancer (BCa) are often invasive and/or possess suboptimal sensitivity and specificity, especially in early-stage, minimal, and residual tumors.METHODSWe developed an efficient method, termed utMeMA, for the detection of urine tumor DNA methylation at multiple genomic regions by MassARRAY. We identified the BCa-specific methylation markers by combined analyses of cohorts from Sun Yat-sen Memorial Hospital (SYSMH), The Cancer Genome Atlas (TCGA), and the Gene Expression Omnibus (GEO) database. The BCa diagnostic model was built in a retrospective cohort (n = 313) and validated in a multicenter, prospective cohort (n = 175). The performance of this diagnostic assay was analyzed and compared with urine cytology and FISH.RESULTSWe first discovered 26 significant methylation markers of BCa in combined analyses. We built and validated a 2-marker-based diagnostic model that discriminated among patients with BCa with high accuracy (86.7%), sensitivity (90.0%), and specificity (83.1%). Furthermore, the utMeMA-based assay achieved a great improvement in sensitivity over urine cytology and FISH, especially in the detection of early-stage (stage Ta and low-grade tumor, 64.5% vs. 11.8%, 15.8%), minimal (81.0% vs. 14.8%, 37.9%), residual (93.3% vs. 27.3%, 64.3%), and recurrent (89.5% vs. 31.4%, 52.8%) tumors. The urine diagnostic score from this assay was better associated with tumor malignancy and burden.CONCLUSIONUrine tumor DNA methylation assessment for early diagnosis, minimal, residual tumor detection and surveillance in BCa is a rapid, high-throughput, noninvasive, and promising approach, which may reduce the burden of cystoscopy and blind second surgery.FUNDINGThis study was supported by the National Key Research and Development Program of China and the National Natural Science Foundation of China.
Topics: Aged; Biomarkers, Tumor; DNA Methylation; DNA, Neoplasm; Early Detection of Cancer; Female; Humans; Male; Middle Aged; Retrospective Studies; Urinary Bladder Neoplasms
PubMed: 32817589
DOI: 10.1172/JCI139597