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Cancers
Special Issues
Systemic Treatment of Advanced Bladder Cancer – Status Update
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Systemic Treatment of Advanced Bladder Cancer – Status Update

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Therapy".

Deadline for manuscript submissions: closed (31 December 2021) | Viewed by 16790

Special Issue Editors

Prof. Helle Pappot

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Guest Editor
Department of Oncology, Team Urooncology, Rigshospitalet, University Hospital of Copenhagen, Blegdamsvej 9, 2100 Copenhagen, Denmark
Interests: bladder cancer; urooncology; chemotherapy; immunotherapy; patient reported outcome; patientinvolvement; quality of life; selection markers
Dr. Anders Ullen

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Guest Editor
1. Patient Area Pelvic Cancer, Theme Cancer, Karolinska University Hospital,17176 Stockholm, Sweden; 2. Department of Oncology-Pathology, Karolinska Institute, 17176 Stockholm, Sweden
Interests: bladder cancer; urothelial cancer; systemic treatment; immunotherapy; biomarkers; precision cancer medicine; multiplex immunohistochemistry; digital image analysis; targeted sequencing; ctDNA

Special Issue Information

Dear Colleagues,

Bladder cancer is diagnosed in more than 400,000 cases annually worldwide, and it represents the sixth most common malignancy in the Western world. Since the mid-80s, systemic treatment of advanced disease has been limited to platinum-based combination chemotherapy, with few treatment options upon progression and with poor overall survival. The very recent advance introducing immune checkpoint inhibitors (ICIs), antibody–drug conjugates (ADCs), and tyrosine kinase inhibitors (TKIs) alongside standard, conventional chemotherapies are, however, changing the paradigm of systemic treatment of advanced UC. With the introduction of these new compounds, there is new hope for patients with advanced urothelial bladder cancer. A myriad of trials are evaluating these and other novel compounds in combination and at different stages of the disease. Further, the cancer trajectory for a patient with advanced bladder cancer receiving systemic treatment may be influenced by multiple factors, with the outcome dependent on both new biological knowledge as well as optimal supportive care. In this issue, we would like to present the present status of systemic treatment of advanced bladder cancer, covering the spectrum from selection markers to best antineoplastic treatment but also including improved symptom management and issues regarding quality of life in this often vulnerable patient population.

Prof. Helle Pappot
Dr. Anders Ullen
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • metastatic disease
  • neoadjuvant treatment
  • adjuvant treatment
  • maintenance treatment
  • checkpoint inhibitors
  • chemotherapy
  • tyrosine kinase inhibitors
  • quality of life
  • symptom management
  • survival

Published Papers (8 papers)

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Editorial

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4 pages, 212 KiB  
Editorial
Optimal Systemic Treatment of Advanced Bladder Cancer Calls for a Multidisciplinary Approach
by Helle Pappot and Anders Ullén
Cancers 2023, 15(3), 559; https://doi.org/10.3390/cancers15030559 - 17 Jan 2023
Viewed by 1243
Abstract
Although the bladder cancer treatment field is expanding with several new treatments introduced in the last decade, many patients with an advanced form of the disease can expect a poor prognosis when diagnosed [...] Full article
(This article belongs to the Special Issue Systemic Treatment of Advanced Bladder Cancer – Status Update)
3 pages, 200 KiB  
Editorial
Optimal Systemic Treatment of Advanced Bladder Cancer—A Moving Target
by Helle Pappot and Anders Ullén
Cancers 2020, 12(12), 3607; https://doi.org/10.3390/cancers12123607 - 2 Dec 2020
Cited by 1 | Viewed by 1092
Abstract
n/a Full article
(This article belongs to the Special Issue Systemic Treatment of Advanced Bladder Cancer – Status Update)

Research

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11 pages, 899 KiB  
Article
Efficacy of Vinflunine for Patients with Metastatic Urothelial Cancer after Immune Checkpoint Inhibitor Pretreatment—A Retrospective Multicenter Analysis
by Felix Riedel, Mara Münker, Florian Roghmann, Johannes Breyer, Marco J. Schnabel, Maximilian Burger, Danijel Sikic, Thomas Büttner, Manuel Ritter, Kiriaki Hiller, Felix Wezel, Christian Bolenz and Friedemann Zengerling
Cancers 2022, 14(12), 2850; https://doi.org/10.3390/cancers14122850 - 9 Jun 2022
Cited by 4 | Viewed by 1687
Abstract
Background: Immune checkpoint inhibitors (ICI) are standard of care in patients with metastatic urothelial carcinoma (mUC) ineligible for cisplatin, and as second-line therapy after platinum-based chemotherapy. To date, few data exist about the efficacy of the former second-line chemotherapeutic agent vinflunine after the [...] Read more.
Background: Immune checkpoint inhibitors (ICI) are standard of care in patients with metastatic urothelial carcinoma (mUC) ineligible for cisplatin, and as second-line therapy after platinum-based chemotherapy. To date, few data exist about the efficacy of the former second-line chemotherapeutic agent vinflunine after the failure of sequential platinum-based chemotherapy and ICI treatment. The aim of this analysis was to examine the efficacy of vinflunine in a post-ICI third- or later-line setting. Methods: In this retrospective German multicenter study, data of mUC patients treated with vinflunine were reviewed in six centers between February 2010 and December 2021. All of the 105 included patients had radiologic progression after first-line platinum-based chemotherapy. The objective was to describe the efficacy of vinflunine in terms of overall response rate (ORR), clinical benefit rate (CBR), overall survival (OS), and progression-free survival (PFS) for post-ICI and ICI-naïve patients, respectively. Results: In our cohort, 61 patients (58.1%) had preceding immunotherapy before vinflunine administration, and 44 patients (41.9%) were ICI-naïve. Patients with ICI pretreatment showed an ORR of 22.4% compared to 15.6% within ICI-naïve patients (p = 0.451), and CBR was 51.0% vs. 25.0% (p = 0.020), respectively. Post-ICI patients showed longer OS (8.78 vs. 5.72 months; p = 0.467) and longer PFS (3.09 vs. 2.14 months; p = 0.105). Conclusion: This analysis supports the sequential use of vinflunine in post-ICI patients since the vinca-alkaloid retains a measurable clinical activity in these heavily pretreated patients. The therapeutic benefit may be higher than demonstrated in previous studies. Full article
(This article belongs to the Special Issue Systemic Treatment of Advanced Bladder Cancer – Status Update)
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13 pages, 3002 KiB  
Article
Circulating Forms of Urokinase-Type Plasminogen Activator Receptor in Plasma Can Predict Recurrence and Survival in Patients with Urothelial Carcinoma of the Bladder
by Line H. Dohn, Peter Thind, Lisbeth Salling, Henriette Lindberg, Sofie Oersted, Ib J. Christensen, Ole D. Laerum, Martin Illemann, Hans von der Maase, Gunilla Høyer-Hansen and Helle Pappot
Cancers 2021, 13(10), 2377; https://doi.org/10.3390/cancers13102377 - 14 May 2021
Cited by 4 | Viewed by 1700
Abstract
Urothelial carcinoma of the bladder is a highly aggressive disease characterised by a very heterogeneous clinical outcome. Despite cystectomy, patients still have a high recurrence risk and shortened survival. Urokinase-type plasminogen activator receptor (uPAR) is present in tumour tissue specimens from patients with [...] Read more.
Urothelial carcinoma of the bladder is a highly aggressive disease characterised by a very heterogeneous clinical outcome. Despite cystectomy, patients still have a high recurrence risk and shortened survival. Urokinase-type plasminogen activator receptor (uPAR) is present in tumour tissue specimens from patients with urothelial carcinoma. The different uPAR forms in blood are strong prognostic markers in other cancer types. We investigate the presence of different uPAR forms in tumour tissue and test the hypothesis that preoperative plasma levels of the uPAR forms predict recurrence free survival, cancer specific survival, and overall survival in patients treated with cystectomy for urothelial carcinoma. Using Western blotting we analyse neoplasia and adjacent benign-appearing urothelium from randomly selected patients for the presence of intact and cleaved uPAR forms. Prospectively collected preoperative plasma samples from 107 patients who underwent radical cystectomy for urothelial carcinoma are analysed. The different uPAR forms are measured by time-resolved fluorescence immunoassays. uPAR in tumour tissue from patients with urothelial carcinoma is demonstrated in both an intact and cleaved form. The different uPAR forms in plasma are all significantly associated with both recurrence free survival, cancer specific survival, and overall survival, high concentrations predicting short survival. uPAR (I) has the strongest association with a HR of 2.56 for overall survival. In the multivariable survival analysis uPAR (I) is significantly associated with cancer specific survival and overall survival. Full article
(This article belongs to the Special Issue Systemic Treatment of Advanced Bladder Cancer – Status Update)
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Review

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17 pages, 326 KiB  
Review
Molecular Subtypes as a Basis for Stratified Use of Neoadjuvant Chemotherapy for Muscle-Invasive Bladder Cancer—A Narrative Review
by Gottfrid Sjödahl, Johan Abrahamsson, Carina Bernardo, Pontus Eriksson, Mattias Höglund and Fredrik Liedberg
Cancers 2022, 14(7), 1692; https://doi.org/10.3390/cancers14071692 - 26 Mar 2022
Cited by 10 | Viewed by 2261
Abstract
There are no established biomarkers to guide patient selection for neoadjuvant chemotherapy prior to radical cystectomy for muscle-invasive bladder cancer. Recent studies suggest that molecular subtype classification holds promise for predicting chemotherapy response and/or survival benefit in this setting. Here, we summarize and [...] Read more.
There are no established biomarkers to guide patient selection for neoadjuvant chemotherapy prior to radical cystectomy for muscle-invasive bladder cancer. Recent studies suggest that molecular subtype classification holds promise for predicting chemotherapy response and/or survival benefit in this setting. Here, we summarize and discuss the scientific literature examining transcriptomic or panel-based molecular subtyping applied to neoadjuvant chemotherapy-treated patient cohorts. We find that there is not sufficient evidence to conclude that the basal subtype of muscle-invasive bladder cancer responds well to chemotherapy, since only a minority of studies support this conclusion. More evidence indicates that luminal-like subtypes may have the most improved outcomes after neoadjuvant chemotherapy. There are also conflicting data concerning the association between biopsy stromal content and response. Subtypes indicative of high stromal infiltration responded well in some studies and poorly in others. Uncertainties when interpreting the current literature include a lack of reporting both response and survival outcomes and the inherent risk of bias in retrospective study designs. Taken together, available studies suggest a role for molecular subtyping in stratifying patients for receiving neoadjuvant chemotherapy. The precise classification system that best captures such a predictive effect, and the exact subtypes for which other treatment options are more beneficial remains to be established, preferably in prospective studies. Full article
(This article belongs to the Special Issue Systemic Treatment of Advanced Bladder Cancer – Status Update)
15 pages, 908 KiB  
Review
Management of Patients with Metastatic Bladder Cancer in the Real-World Setting from the Multidisciplinary Team: Current Opinion of the SOGUG Multidisciplinary Working Group
by Aránzazu González-del-Alba, Antonio José Conde-Moreno, Ana M. García Vicente, Pilar González-Peramato, Estefanía Linares-Espinós, Miguel Ángel Climent and the SOGUG Multidisciplinary Working Group
Cancers 2022, 14(5), 1130; https://doi.org/10.3390/cancers14051130 - 23 Feb 2022
Cited by 4 | Viewed by 2603
Abstract
Based on the discussion of current state of research of relevant topics of metastatic bladder cancer (mBC) among a group of experts of a Spanish Oncology Genitourinary (SOGUG) Working Group, a set of recommendations were proposed to overcome the challenges posed by the [...] Read more.
Based on the discussion of current state of research of relevant topics of metastatic bladder cancer (mBC) among a group of experts of a Spanish Oncology Genitourinary (SOGUG) Working Group, a set of recommendations were proposed to overcome the challenges posed by the management of mBC in clinical practice. First-line options in unfit patients for cisplatin are chemotherapy with carboplatin and immunotherapy in PD-L1 positive patients. FDG-PET/CT may be a useful imaging technique in the initial staging or re-staging. In patients with oligometastatic disease, it is important to consider not only the number of metastatic lesions, but also the tumor biology and the clinical course. The combination of stereotactic body radiotherapy and immunotherapy with anti-PD-L1 monoclonal antibodies is under investigation and could improve the results of systemic treatment in patient with oligometastatic disease. Rescue treatment with curative intent could be considered in patients with oligometastatic disease after complete response on FDG-PET/CT. Metastatic disease should be evaluated using the same imaging modality over the course of the disease from diagnosis until rescue treatment. For improving the outcome of patients with mBC, the involvement of a dedicated multidisciplinary team, including urologists, pathologists, oncologists, radiologists and other specialists is of outmost importance in the daily care of these patients. Full article
(This article belongs to the Special Issue Systemic Treatment of Advanced Bladder Cancer – Status Update)
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14 pages, 8959 KiB  
Review
Tumor Heterogeneity and Consequences for Bladder Cancer Treatment
by Etienne Lavallee, John P. Sfakianos and David J. Mulholland
Cancers 2021, 13(21), 5297; https://doi.org/10.3390/cancers13215297 - 22 Oct 2021
Cited by 14 | Viewed by 3457
Abstract
Acquired therapeutic resistance remains a major challenge in cancer management and associates with poor oncological outcomes in most solid tumor types. A major contributor is tumor heterogeneity (TH) which can be influenced by the stromal; immune and epithelial tumor compartments. We hypothesize that [...] Read more.
Acquired therapeutic resistance remains a major challenge in cancer management and associates with poor oncological outcomes in most solid tumor types. A major contributor is tumor heterogeneity (TH) which can be influenced by the stromal; immune and epithelial tumor compartments. We hypothesize that heterogeneity in tumor epithelial subpopulations—whether de novo or newly acquired—closely regulate the clinical course of bladder cancer. Changes in these subpopulations impact the tumor microenvironment including the extent of immune cell infiltration and response to immunotherapeutics. Mechanisms driving epithelial tumor heterogeneity (EpTH) can be broadly categorized as mutational and non-mutational. Mechanisms regulating lineage plasticity; acquired cellular mutations and changes in lineage-defined subpopulations regulate stress responses to clinical therapies. If tumor heterogeneity is a dynamic process; an increased understanding of how EpTH is regulated is critical in order for clinical therapies to be more sustained and durable. In this review and analysis, we assess the importance and regulatory mechanisms governing EpTH in bladder cancer and the impact on treatment response. Full article
(This article belongs to the Special Issue Systemic Treatment of Advanced Bladder Cancer – Status Update)
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Other

14 pages, 7866 KiB  
Systematic Review
Metastasis-Directed Radiation Therapy with Consolidative Intent for Oligometastatic Urothelial Carcinoma: A Systematic Review and Meta-Analysis
by Nicola Longo, Giuseppe Celentano, Luigi Napolitano, Roberto La Rocca, Marco Capece, Gianluigi Califano, Claudia Collà Ruvolo, Francesco Mangiapia, Ferdinando Fusco, Simone Morra, Carmine Turco, Francesco Di Bello, Giovanni Maria Fusco, Luigi Cirillo, Crescenzo Cacciapuoti, Lorenzo Spirito, Armando Calogero, Antonello Sica, Caterina Sagnelli and Massimiliano Creta
Cancers 2022, 14(10), 2373; https://doi.org/10.3390/cancers14102373 - 11 May 2022
Cited by 11 | Viewed by 1845
Abstract
The management of patients with oligometastatic urothelial carcinoma (UC) represents an evolving field in uro-oncology, and the role of metastasis-directed therapies, including metastasectomy and metastasis-directed radiation therapy (MDRT), is gaining increasing attention. Herein, we summarize available evidence about the role of MDRT with [...] Read more.
The management of patients with oligometastatic urothelial carcinoma (UC) represents an evolving field in uro-oncology, and the role of metastasis-directed therapies, including metastasectomy and metastasis-directed radiation therapy (MDRT), is gaining increasing attention. Herein, we summarize available evidence about the role of MDRT with consolidative intent in oligometastatic UC patients. A systematic review was performed in December 2021. Six studies involving 158 patients were identified. Most patients (n = 120, 90.2%) had a history of bladder cancer and the most frequent sites of metastases were lymph nodes (n = 61, 52.1%) followed by the lungs (n = 34, 29%). Overall, 144 metastases were treated with MDRT. Median follow-up ranged from 17.2 to 25 months. Local control rates ranged from 57% to 100%. Median Overall Survival (OS) ranged from 14.9 to 51.0 months and median progression-free survival ranged from 2.9 to 10.1 months. Rates of OS at one and two years ranged from 78.9% to 96% and from 26% to 63%, respectively. Treatment-related toxicity was recorded in few patients and in most cases a low-grade toxicity was evident. MDRT with consolidative intent represents a potential treatment option for selected patients with oligometastatic UC. Full article
(This article belongs to the Special Issue Systemic Treatment of Advanced Bladder Cancer – Status Update)
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