-
JAMA Nov 2020Bladder cancer is a common malignancy in women and is the fourth most common malignancy in men. Bladder cancer ranges from unaggressive and usually noninvasive tumors... (Review)
Review
IMPORTANCE
Bladder cancer is a common malignancy in women and is the fourth most common malignancy in men. Bladder cancer ranges from unaggressive and usually noninvasive tumors that recur and commit patients to long-term invasive surveillance, to aggressive and invasive tumors with high disease-specific mortality.
OBSERVATIONS
Advanced age, male sex, and cigarette smoking contribute to the development of bladder cancer. Bladder tumors can present with gross or microscopic hematuria, which is evaluated with cystoscopy and upper tract imaging depending on the degree of hematuria and risk of malignancy. Non-muscle-invasive tumors are treated with endoscopic resection and adjuvant intravesical therapy, depending on the risk classification. Enhanced cystoscopy includes technology used to improve the detection of tumors and can reduce the risk of recurrence. Patients with high-risk non-muscle invasive tumors that do not respond to adjuvant therapy with the standard-of-care immunotherapy, bacille Calmette-Guérin (BCG), constitute a challenging patient population to manage and many alternative therapies are being studied. For patients with muscle-invasive disease, more aggressive therapy with radical cystectomy and urinary diversion or trimodal therapy with maximal endoscopic resection, radiosensitizing chemotherapy, and radiation is warranted to curb the risk of metastasis and disease-specific mortality. Treatment of patients with advanced disease is undergoing rapid changes as immunotherapy with checkpoint inhibitors, targeted therapies, and antibody-drug conjugates have become options for certain patients with various stages of disease.
CONCLUSIONS AND RELEVANCE
Improved understanding of the molecular biology and genetics of bladder cancer has evolved the way localized and advanced disease is diagnosed and treated. While intravesical BCG has remained the mainstay of therapy for intermediate and high-risk non-muscle-invasive bladder cancer, the therapeutic options for muscle-invasive and advanced disease has expanded to include immunotherapy with checkpoint inhibition, targeted therapies, and antibody-drug conjugates.
Topics: Administration, Intravesical; Antineoplastic Agents; BCG Vaccine; Combined Modality Therapy; Cystectomy; Cystoscopy; Female; Humans; Immunotherapy; Male; Mutation; Neoplasm Invasiveness; Risk Factors; Urinary Bladder; Urinary Bladder Neoplasms
PubMed: 33201207
DOI: 10.1001/jama.2020.17598 -
Lancet (London, England) Nov 2022This Seminar presents the current best practice for the diagnosis and management of bladder cancer. The scope of this Seminar ranges from current challenges in... (Review)
Review
This Seminar presents the current best practice for the diagnosis and management of bladder cancer. The scope of this Seminar ranges from current challenges in pathology, such as the evolving histological and molecular classification of disease, to advances in personalised medicine and novel imaging approaches. We discuss the current role of radiotherapy, surgical management of non-muscle-invasive and muscle-invasive disease, highlight the challenges of treatment of metastatic bladder cancer, and discuss the latest developments in systemic therapy. This Seminar is intended to provide physicians with knowledge of current issues in bladder cancer.
Topics: Humans; Urinary Bladder Neoplasms; Neoplasm Invasiveness
PubMed: 36174585
DOI: 10.1016/S0140-6736(22)01188-6 -
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 -
Hematology/oncology Clinics of North... Jun 2021Cystoscopic examination remains the gold standard technique for initial diagnosis of bladder cancer (BCa). Despite significant progress in enhanced cystoscopic... (Review)
Review
Cystoscopic examination remains the gold standard technique for initial diagnosis of bladder cancer (BCa). Despite significant progress in enhanced cystoscopic techniques, blue light cystoscopy and narrow band imaging are the only ones well supported by high-level evidence and, if available, should be used during initial staging of BCa. Multiparametric MRI could be an important imaging tool in local staging of BCa. With ever-expanding targeted therapy and immunotherapy options in both muscle-invasive and non-muscle-invasive BCa, molecular subtyping could become an essential part of initial histologic staging in the near future.
Topics: Cystoscopy; Humans; Neoplasm Staging; Urinary Bladder Neoplasms
PubMed: 33958149
DOI: 10.1016/j.hoc.2021.02.004 -
Drug Resistance Updates : Reviews and... May 2023Bladder cancer is one of the most common malignancies in the world. Cisplatin is one of the most potent and widely used anticancer drugs and has been employed in several... (Review)
Review
Bladder cancer is one of the most common malignancies in the world. Cisplatin is one of the most potent and widely used anticancer drugs and has been employed in several malignancies. Cisplatin-based combination chemotherapies have become important adjuvant therapies for bladder cancer patients. Cisplatin-based treatment often results in the development of chemoresistance, leading to therapeutic failure and limiting its application and effectiveness in bladder cancer. To develop improved and more effective cancer therapy, research has been conducted to elucidate the underlying mechanism of cisplatin resistance. Epigenetic modifications have been demonstrated involved in drug resistance to chemotherapy, and epigenetic biomarkers, such as urine tumor DNA methylation assay, have been applied in patients screening or monitoring. Here, we provide a systematic description of epigenetic mechanisms, including DNA methylation, noncoding RNA regulation, m6A modification and posttranslational modifications, related to cisplatin resistance in bladder cancer.
Topics: Humans; Cisplatin; Drug Resistance, Neoplasm; Urinary Bladder Neoplasms; Epigenesis, Genetic; Methylation; Cell Line, Tumor; Antineoplastic Agents
PubMed: 36774746
DOI: 10.1016/j.drup.2023.100938 -
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 -
European Urology Jan 2021This overview presents the updated European Association of Urology (EAU) guidelines for muscle-invasive and metastatic bladder cancer (MMIBC). (Review)
Review
CONTEXT
This overview presents the updated European Association of Urology (EAU) guidelines for muscle-invasive and metastatic bladder cancer (MMIBC).
OBJECTIVE
To provide practical evidence-based recommendations and consensus statements on the clinical management of MMIBC with a focus on diagnosis and treatment.
EVIDENCE ACQUISITION
A broad and comprehensive scoping exercise covering all areas of the MMIBC guideline has been performed annually since its 2017 publication (based on the 2016 guideline). Databases covered by the search included Medline, EMBASE, and the Cochrane Libraries, resulting in yearly guideline updates. A level of evidence and a grade of recommendation were assigned. Additionally, the results of a collaborative multistakeholder consensus project on advanced bladder cancer (BC) have been incorporated in the 2020 guidelines, addressing those areas where it is unlikely that prospective comparative studies will be conducted.
EVIDENCE SYNTHESIS
Variant histologies are increasingly reported in invasive BC and are relevant for treatment and prognosis. Staging is preferably done with (enhanced) computerised tomography scanning. Treatment decisions are still largely based on clinical factors. Radical cystectomy (RC) with lymph node dissection remains the recommended treatment in highest-risk non-muscle-invasive and muscle-invasive nonmetastatic BC, preceded by cisplatin-based neoadjuvant chemotherapy (NAC) for invasive tumours in "fit" patients. Selected men and women benefit from sexuality sparing RC, although this is not recommended as standard therapy. Open and robotic RC show comparable outcomes, provided the procedure is performed in experienced centres. For open RC 10, the minimum selected case load is 10 procedures per year. If bladder preservation is considered, chemoradiation is an alternative in well-selected patients without carcinoma in situ and after maximal resection. Adjuvant chemotherapy should be considered if no NAC was given. Perioperative immunotherapy can be offered in clinical trial setting. For fit metastatic patients, cisplatin-based chemotherapy remains the first choice. In cisplatin-ineligible patients, immunotherapy in Programmed Death Ligand 1 (PD-L1)-positive patients or carboplatin in PD-L1-negative patients is recommended. For second-line treatment in metastatic disease, pembrolizumab is recommended. Postchemotherapy surgery may prolong survival in responders. Quality of life should be monitored in all phases of treatment and follow-up. The extended version of the guidelines is available at the EAU website: https://uroweb.org/guideline/bladder-cancer-muscle-invasive-and-metastatic/.
CONCLUSIONS
This summary of the 2020 EAU MMIBC guideline provides updated information on the diagnosis and treatment of MMIBC for incorporation into clinical practice.
PATIENT SUMMARY
The European Association of Urology Muscle-invasive and Metastatic Bladder Cancer (MMIBC) Panel has released an updated version of their guideline, which contains information on histology, staging, prognostic factors, and treatment of MMIBC. The recommendations are based on the current literature (until the end of 2019), with emphasis on high-level data from randomised clinical trials and meta-analyses and on the findings of an international consensus meeting. Surgical removal of the bladder and bladder preservation are discussed, as well as the use of chemotherapy and immunotherapy in localised and metastatic disease.
Topics: Decision Trees; Humans; Neoplasm Invasiveness; Neoplasm Metastasis; Urinary Bladder Neoplasms
PubMed: 32360052
DOI: 10.1016/j.eururo.2020.03.055 -
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