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Time for a Paradigm Shift in Non-muscle-invasive Bladder Cancer (Volume...
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Time for a Paradigm Shift in Non-muscle-invasive Bladder Cancer (Volume II)

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

Deadline for manuscript submissions: closed (20 March 2024) | Viewed by 9949

Special Issue Editor

Prof. Dr. Jørgen Bjerggaard Jensen

E-Mail Website
Guest Editor
Department of Clinical Medicine, Aarhus University, 8200 Aarhus, Denmark
Interests: bladder cancer; UTUC; robotic surgery
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue is entitled “Time for a Paradigm Shift in Non-muscle Invasive Bladder Cancer” and is available at https://www.mdpi.com/journal/cancers/special_issues/Paradigm_Shift_Bladder_Cancer

Non-muscle-invasive bladder cancer (NMIBC) is a highly varied heterogeneous disease with a variety of treatment modalities and different follow-up regimens. Most cases of NMIBC are treated with TURBT and potential adjuvant instillation therapy, whereas the minority can be treated via radical cystectomy. However, despite the utilization of a variety of treatment modalities over the last few decades, a recurrence rate of more than 50% of all patients highlights the urgent need for the development of a better frontline treatment. Moreover, the decades-old use of piecemeal TURBT in NMIBC violates normal oncological principles and the deployment of life-long follow-up regimens based on traditional pathological risk stratification in a disease that has been studied for decades call for a change.

In this Special Issue of Cancers, we will highlight studies where traditional approaches to NMIBC are questioned and challenged and in which new treatment regimens are investigated.

Prof. Dr. Jørgen Bjerggaard Jensen
Guest Editor

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 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

  • non-muscle-invasive bladder cancer
  • treatment
  • instillation
  • follow-up
  • challenge

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Published Papers (5 papers)

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Research

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13 pages, 1052 KiB  
Article
Use of Bladder-Related Medication in Non-Muscle Invasive Bladder Cancer Patients
by Linea Blichert-Refsgaard, Charlotte Graugaard-Jensen, Mette Nørgaard and Jørgen Bjerggaard Jensen
Cancers 2024, 16(10), 1936; https://doi.org/10.3390/cancers16101936 - 20 May 2024
Cited by 1 | Viewed by 1296
Abstract
Repeated transurethral bladder resections (TURBs) and instillation treatments in non-muscle invasive bladder cancer (NMIBC) might influence bladder function and, therefore, quality of life. Bladder-related medication is a surrogate marker of compromised bladder function. The objective was to investigate whether TURBs and adjuvant instillation [...] Read more.
Repeated transurethral bladder resections (TURBs) and instillation treatments in non-muscle invasive bladder cancer (NMIBC) might influence bladder function and, therefore, quality of life. Bladder-related medication is a surrogate marker of compromised bladder function. The objective was to investigate whether TURBs and adjuvant instillation therapy are associated with the use of anticholinergics, β3-agonists, and cystitis-relevant antibiotics. We divided all Danish patients diagnosed with primary NMIBC during 2002–2017 registered in the Danish National Patient Registry (DNPR) based on TURB-load within the first five years from diagnosis (1 TURB, 2–4 TURBs, ≥5 TURBs). Instillation therapy with either mitomycin C (MMC) or bacillus Calmette-Guerin vaccine (BCG) was independent exposure (yes or no). We included 17,774 patients; 76% men, median age: 70 years (IQR: 63, 77). Patients exposed to ≥5 TURBs had a higher risk of using bladder-relaxing medication than patients exposed to 1 TURB, HR = 4.01 [3.33; 4.83], and higher risk of cystitis, HR = 2.27 [2.05; 2.51]. BCG-exposed patients had a higher risk of bladder-relaxing medication use compared to non-exposed, HR = 1.92 [1.69; 2.18], and a higher risk of cystitis, HR = 1.39 [1.31; 1.48]. Repeated TURBs have the highest impact on bladder function. Adjuvant instillation therapy is also associated with the use of bladder-related medication. Full article
(This article belongs to the Special Issue Time for a Paradigm Shift in Non-muscle-invasive Bladder Cancer (Volume II))
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16 pages, 5409 KiB  
Article
PD-L1 Expression in High-Risk Non-Muscle-Invasive Bladder Cancer Is Influenced by Intravesical Bacillus Calmette–Guérin (BCG) Therapy
by Moritz Maas, Andreas Hilsendecker, Alexandra Pertoll, Viktoria Stühler, Simon Walz, Steffen Rausch, Arnulf Stenzl, Igor Tsaur, Jörg Hennenlotter and Stefan Aufderklamm
Cancers 2024, 16(7), 1356; https://doi.org/10.3390/cancers16071356 - 29 Mar 2024
Viewed by 1428
Abstract
In the expanding landscape of immune checkpoint inhibitors (CPI) in high-risk (HR) non-muscle-invasive bladder cancer (NMIBC), the role of programmed death ligand 1 (PD-L1) as prognostic and predictive is increasingly significant. However, data evaluating its variability and susceptibility to Bacillus Calmette–Guérin (BCG) therapy [...] Read more.
In the expanding landscape of immune checkpoint inhibitors (CPI) in high-risk (HR) non-muscle-invasive bladder cancer (NMIBC), the role of programmed death ligand 1 (PD-L1) as prognostic and predictive is increasingly significant. However, data evaluating its variability and susceptibility to Bacillus Calmette–Guérin (BCG) therapy in HR NMIBC patients is scarce. This retrospective study analyzed 126 HR NMIBC tissue samples from 63 patients (38× BCG-treated, 25× BCG-naïve) at two time points to assess PD-L1 expression using the ‘combined positivity score’ (CPS) with the 22C3 DAKO antibody method and correlated it with clinicopathological parameters. A CPS > 10 defined PD-L1 positivity. The impact of initial PD-L1 status and its change over time on time-to-recurrence, progression-free survival, and overall survival (TTR, PFS, OS) was analyzed using Kaplan–Meier and Cox proportional hazard models. BCG treatment significantly increased PD-L1 expression (5.31 vs. 0.22, p = 0.0423), with PD-L1 positive cases rising post-treatment in the BCG group and remaining unchanged in BCG-naïve patients. Multivariate analysis including T-stage, CIS, grading, tumor size, multifocality, age, and sex revealed a significant correlation between PD-L1 status change to positivity and improved TTR (p = 0.03). Our findings demonstrate a potential modulation of the PD-L1 status by an intravesical BCG therapy. However, its prognostic value appears limited. Full article
(This article belongs to the Special Issue Time for a Paradigm Shift in Non-muscle-invasive Bladder Cancer (Volume II))
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Review

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20 pages, 2232 KiB  
Review
Photodynamic Diagnosis and Therapy in Non-Muscle-Invasive Bladder Cancer
by Atsushi Kurabayashi, Hideo Fukuhara, Kaoru Furihata, Waka Iwashita, Mutsuo Furihata and Keiji Inoue
Cancers 2024, 16(13), 2299; https://doi.org/10.3390/cancers16132299 - 22 Jun 2024
Viewed by 1366
Abstract
Bladder cancer (BC) possesses distinct molecular profiles that influence progression depending on its biological nature and delivered treatment intensity. Muscle-invasive BC (MIBC) and non-MIBC (NMIBC) demonstrate great intrinsic heterogeneity regarding different prognoses, survival, progression, and treatment outcomes. Transurethral resection of bladder tumor (TURBT) [...] Read more.
Bladder cancer (BC) possesses distinct molecular profiles that influence progression depending on its biological nature and delivered treatment intensity. Muscle-invasive BC (MIBC) and non-MIBC (NMIBC) demonstrate great intrinsic heterogeneity regarding different prognoses, survival, progression, and treatment outcomes. Transurethral resection of bladder tumor (TURBT) is the standard of care in treating NMIBC and serves both diagnostic and therapeutic purposes despite the prevalent recurrence and progression among many patients. In particular, flat urothelial carcinoma in situ and urothelial carcinoma with lamina propria invasion are the major precursors of MIBC. A new-generation photosensitizer, 5-Aminolevulinic acid (5-ALA), demonstrates high tumor specificity by illuminating the tumor lesion with a specific wavelength of light to produce fluorescence and has been studied for photodynamic diagnosis to detect precise tumor areas by TURBT. Additionally, it has been applied for treatment by producing its cytotoxic reactive oxygen species, as well as screening for urological carcinomas by excreting porphyrin in the blood and urine. Moreover, 5-ALA may contribute to screening before and after TURBT in NMIBC. Here, we summarize the updated evidence and ongoing research on photodynamic technology for NMIBC, providing insight into the potential for improving patient outcomes. Full article
(This article belongs to the Special Issue Time for a Paradigm Shift in Non-muscle-invasive Bladder Cancer (Volume II))
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18 pages, 302 KiB  
Review
Treatment Modalities for Non-Muscle Invasive Bladder Cancer: An Updated Review
by Shannon McNall, Kailey Hooper, Travis Sullivan, Kimberly Rieger-Christ and Matthew Clements
Cancers 2024, 16(10), 1843; https://doi.org/10.3390/cancers16101843 - 11 May 2024
Cited by 1 | Viewed by 2682
Abstract
The landscape of treatment for non-muscle invasive bladder cancer is rapidly changing. A complete and careful transurethral resection is the mainstay of initial treatment and is followed by intravesical therapy in intermediate or high-risk cases. The standard of care is intravesical BCG. Many [...] Read more.
The landscape of treatment for non-muscle invasive bladder cancer is rapidly changing. A complete and careful transurethral resection is the mainstay of initial treatment and is followed by intravesical therapy in intermediate or high-risk cases. The standard of care is intravesical BCG. Many alternative or additive approaches to this are being explored. We divided this review into three relevant spaces to consider these novel treatment approaches: (1) low-risk disease, for which intravesical therapy is not usually considered, (2) BCG-naïve disease (i.e., considering alternatives to the standard therapy), and (3) BCG-unresponsive disease. We performed a review of published literature and summarized ongoing trials in the United States. Novel approaches that we explored include surgical techniques for resection, alterations in dwell time for intravesical therapy, delivery method and schedule of intravesical therapies, new intravesical therapy agents, and systemic therapies (especially immunotherapy). These are thoroughly outlined throughout this review article, and the numerous modalities being studied demonstrate significant promise for the future treatment of the expanding space of NMIBC. Full article
(This article belongs to the Special Issue Time for a Paradigm Shift in Non-muscle-invasive Bladder Cancer (Volume II))
14 pages, 277 KiB  
Review
Revolutionizing Treatment: Breakthrough Approaches for BCG-Unresponsive Non-Muscle-Invasive Bladder Cancer
by Maciej Jaromin, Tomasz Konecki and Piotr Kutwin
Cancers 2024, 16(7), 1366; https://doi.org/10.3390/cancers16071366 - 30 Mar 2024
Cited by 3 | Viewed by 2420
Abstract
Bladder cancer is the 10th most popular cancer in the world, and non-muscle-invasive bladder cancer (NMIBC) is diagnosed in ~80% of all cases. Treatments for NMIBC include transurethral resection of the bladder tumor (TURBT) and intravesical instillations of Bacillus Calmette-Guérin (BCG). Treatment of [...] Read more.
Bladder cancer is the 10th most popular cancer in the world, and non-muscle-invasive bladder cancer (NMIBC) is diagnosed in ~80% of all cases. Treatments for NMIBC include transurethral resection of the bladder tumor (TURBT) and intravesical instillations of Bacillus Calmette-Guérin (BCG). Treatment of BCG-unresponsive tumors is scarce and usually leads to Radical Cystectomy. In this paper, we review recent advancements in conservative treatment of BCG-unresponsive tumors. The main focus of the paper is FDA-approved medications: Pembrolizumab and Nadofaragene Firadenovec (Adstiladrin). Other, less researched therapeutic possibilities are also included, namely: N-803 immunotherapy, TAR-200 and TAR-210 intravesical delivery systems and combined Cabazitaxel, Gemcitabine and Cisplatin chemotherapy. Conservative treatment and delaying radical cystectomy would greatly benefit patients’ quality of life; it is undoubtedly the future of BCG-unresponsive NMIBC. Full article
(This article belongs to the Special Issue Time for a Paradigm Shift in Non-muscle-invasive Bladder Cancer (Volume II))
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