Dataset Information

Evolution of Urothelial Bladder Cancer in the Context of Molecular Classifications.

ABSTRACT: Bladder cancer is a heterogeneous disease that is not depicted by current classification systems. It was originally classified into non-muscle invasive and muscle invasive. However, clinically and genetically variable tumors are summarized within both classes. A definition of three groups may better account for the divergence in prognosis and probably also choice of treatment. The first group represents mostly non-invasive tumors that reoccur but do not progress. Contrarily, the second group represent non-muscle invasive tumors that likely progress to the third group, the muscle invasive tumors. High throughput tumor profiling improved our understanding of the biology of bladder cancer. It allows the identification of molecular subtypes, at least three for non-muscle invasive bladder cancer (Class I, Class II and Class III) and six for muscle-invasive bladder cancer (luminal papillary, luminal non-specified, luminal unstable, stroma-rich, basal/squamous and neuroendocrine-like) with distinct clinical and molecular phenotypes. Molecular subtypes can be potentially used to predict the response to treatment (e.g., neoadjuvant chemotherapy and immune checkpoint inhibitors). Moreover, they may allow to characterize the evolution of bladder cancer through different pathways. However, to move towards precision medicine, the understanding of the biological meaning of these molecular subtypes and differences in the composition of cell subpopulations will be mandatory.

SUBMITTER: Minoli M

PROVIDER: S-EPMC7461199 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Evolution of Urothelial Bladder Cancer in the Context of Molecular Classifications.

Minoli Martina M Kiener Mirjam M Thalmann George N GN Kruithof-de Julio Marianna M Seiler Roland R

International journal of molecular sciences 20200807 16

Bladder cancer is a heterogeneous disease that is not depicted by current classification systems. It was originally classified into non-muscle invasive and muscle invasive. However, clinically and genetically variable tumors are summarized within both classes. A definition of three groups may better account for the divergence in prognosis and probably also choice of treatment. The first group represents mostly non-invasive tumors that reoccur but do not progress. Contrarily, the second group rep ...[more]

PMID: 32784716

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Project description:Urothelial bladder cancer (UBC) is the ninth most common cancer worldwide. In Italy, the prevalence of the disease is approximately 10%, making it the fourth most prevalent cancer in the country. The increase in prevalence requires continuous surveillance and care, resulting in a significant burden on Italian National Health Service, making any improvement to the strategy for diagnosing and treating this disease important to the medical and scientific community. The aim of this study was to evaluate the UBC cost of illness in the Italian context, collecting the total costs of the disease.An economic analysis was carried out in the context of the National Health Service, using data collected from six centers, in order to evaluate direct costs in terms of outpatient, inpatient, and emergency care; pharmaceuticals and follow-up procedures; and indirect costs in terms of productivity losses. Data were collected through aggregated form reports, focusing on patients with an existing diagnosis of UBC who were treated in the last year. The Italian Association of Medical Oncology (AIOM) guidelines were used to identify diagnostic and therapeutic procedures. Statistical analysis was conducted to explore variations among centers.The weighted mean total annual cost per patient was € 3,591, where the cost for superficial disease was € 3,252 and that for metastatic disease was € 606. The analysis confirmed a proportional relation between disease severity and disability grade. The UBC cost of illness, considering prevalence and incidence data coming from the 2016 AIOM/Italian Association of Cancer Registries report, was € 1,187,036,344. Indirect costs accounted to 44%, represented by estimated productivity losses.Our analysis represents the first economic study of UBC in the Italian context, as well as the first real-life evidence of the current therapeutic algorithm. This study opens the possibility for further analysis on the indirect cost components that represent a great burden for the society, especially for those in the severest stages of the disease with high disability grades.

Project description:Background and aimUrothelial bladder cancer (UBC) is a common malignant tumor of the urogenital system with a high rate of recurrence. Due to the sophisticated and largely unexplored mechanisms of tumorigenesis of UBC, the classical therapeutic approaches including transurethral resection and radical cystectomy combined with chemotherapy have remained unchanged for decades. However, with increasingly in-depth understanding of the microenvironment and the composition of tumor-infiltrating lymphocytes of UBC, novel immunotherapeutic strategies have been developed. Bacillus Calmette-Guerin (BCG) therapy, immune checkpoint blockades, adoptive T cell immunotherapy, dendritic cell (DC) vaccines, etc., have all been intensively investigated as immunotherapies for UBC. This review will discuss the recent progress in immune escape mechanisms and immunotherapy of UBC.MethodsBased on a comprehensive search of the PubMed and ClinicalTrials.gov database, this review included the literature reporting the immune escape mechanisms of UBC and clinical trials assessing the effect of immunotherapeutic strategies on tumor or immune cells in UBC patients published in English between 1999 and 2020.ResultsImmune surveillance, immune balance, and immune escape are the three major processes that occur during UBC tumorigenesis. First, the role of immunosuppressive cells, immunosuppressive molecules, immunosuppressive signaling molecules, and DCs in tumor microenvironment is introduced elaborately in the immune escape mechanisms of UBC section. In addition, recent progress of immunotherapies including BCG, checkpoint inhibitors, cytokines, adoptive T cell immunotherapy, DCs, and macrophages on UBC patients are summarized in detail. Finally, the need to explore the mechanisms, molecular characteristics and immune landscape during UBC tumorigenesis and development of novel and robust immunotherapies for UBC are also proposed and discussed.ConclusionAt present, BCG and immune checkpoint blockades have been approved by the US Food and Drug Administration for the treatment of UBC patients and have achieved encouraging therapeutic results, expanding the traditional chemotherapy and surgery-based treatment for UBC.Relevance for patientsImmunotherapy has achieved desirable results in the treatment of UBC, which not only improve the overall survival but also reduce the recurrence rate and the occurrence of treatment-related adverse events of UBC patients. In addition, the indicators to predict the effectiveness and novel therapy strategies, such as combination regimen of checkpoint inhibitor with checkpoint inhibitor or chemotherapy, should be further studied.

Dataset Information

Evolution of Urothelial Bladder Cancer in the Context of Molecular Classifications.

Publications

Evolution of Urothelial Bladder Cancer in the Context of Molecular Classifications.

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