Current and Future Bladder Cancer Landscape

A special issue of Current Oncology (ISSN 1718-7729). This special issue belongs to the section "Genitourinary Oncology".

Deadline for manuscript submissions: closed (31 August 2023) | Viewed by 12899

Special Issue Editor


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Guest Editor
1. Faculty of Medical Sciences, State University of Campinas—UNICAMP, Campinas, São Paulo, Brazil
2. Urologic Oncology Department, PUC-Campinas, School of Life Sciences, Pontifical Catholic University of Campinas, Campinas, São Paulo, Brazil
Interests: bladder cancer; diagnosis; prognosis; treatment; epidemiology
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Special Issue Information

Dear Colleagues,

Urothelial carcinoma of the bladder is one of the most prevalent cancers worldwide, diagnosed as non-muscle invasive (NMIBC) in 75% of cases, in which cystoscopy, transurethral resection, and intravesical bacillus Calmette–Guérin (BCG) have withstood the test of time, remaining the gold standards, as well as neo-adjuvant cisplatin-based chemotherapy and cystectomy in the muscle-invasive context.

Since 2016, the bladder cancer treatment scenario has evolved with the introduction of monoclonal antibodies developed to specifically target immune checkpoint molecules, opening new diagnostic, prognostic, therapeutic, and epidemiological paradigms. This Special Issue will cover the present and future of this evolving landscape.

Prof. Dr. Leonardo O. Reis
Guest Editor

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Keywords

  • bladder cancer
  • diagnosis
  • prognosis
  • treatment
  • epidemiology

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Published Papers (4 papers)

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Research

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9 pages, 752 KiB  
Communication
Survival Benefits of Adjuvant Chemotherapy for Positive Soft Tissue Surgical Margins Following Radical Cystectomy in Bladder Cancer with Extravesical Extension
by Prithvi B. Murthy, Shreyas Naidu, Facundo Davaro, Philippe E. Spiess, Logan Zemp, Michael Poch, Rohit Jain, Aram Vosoughi, G. Daniel Grass, Alice Yu, Wade J. Sexton, Scott M. Gilbert and Roger Li
Curr. Oncol. 2023, 30(3), 3223-3231; https://doi.org/10.3390/curroncol30030245 - 10 Mar 2023
Viewed by 1732
Abstract
Introduction and Objective: Muscle invasive bladder cancer with extravesical extension is an aggressive disease entity that requires multimodal therapy. The benefits of adjuvant chemotherapy (AC) in patients with a positive soft-tissue surgical margin (STSM), however, are relatively unknown due to exclusion of this [...] Read more.
Introduction and Objective: Muscle invasive bladder cancer with extravesical extension is an aggressive disease entity that requires multimodal therapy. The benefits of adjuvant chemotherapy (AC) in patients with a positive soft-tissue surgical margin (STSM), however, are relatively unknown due to exclusion of this population in randomized controlled trials of AC. We sought to define survival benefits in this patient population through our institutional bladder cancer database. Methods: Retrospective review of all patients undergoing radical cystectomy for urothelial carcinoma of the bladder from 2004–2020 with ≥pT3b disease irrespective of neoadjuvant chemotherapy (NAC) use was conducted. Progression-free survival (PFS) and overall survival (OS) estimates were obtained using the Kaplan-Meier method with log-rank test, and the Cox-proportional hazards model was used to identify predictors of improved PFS and OS. AC was defined by any chemotherapy use within 90 days of cystectomy, regardless of STSM status. Results: 476 patients with pT3b disease or worse were identified. Median follow-up was 12.3 months. An amount of 21% of patients were treated with AC. An amount of 24% of patients had positive STSM. Median OS for patients with positive STSM was 8.4 months [95% CI 7–11.5] and 18.3 months [95% CI 15.6–20.8] (p < 0.001) for patients with negative STSM. In the overall cohort, positive STSM (HR 1.93, 95% CI 1.45–2.57, p < 0.001), AC use (HR 0.68, 95% CI 0.51–0.90, p = 0.007), and pN1–3 disease (HR 1.47, 95% CI 1.16–1.87, p = 0.002) were independent predictors of OS when adjusted for performance status, pT-stage, and neoadjuvant chemotherapy use. In patients with positive STSM, median survival was seven months [95% CI 5.2–8.4] without AC, compared to 16.2 months [95% CI 11.5–52.5] with AC (p = 0.0038). For patients with negative STSM, median survival was 17.4 months [95% CI 14–20.1] without AC compared to 22.3 months [95% CI 17.2–36.9] with AC (p = 0.23). In patients with positive STSM, AC use was the only factor associated with an OS benefit with a HR of 0.41 (95% CI 0.21–0.78, p = 0.007). In patients with negative STSM, pT4 and pN1–3 disease were the only factors associated with worse overall survival with a HR of 1.32 (95% CI 1.00–1.74, p = 0.050) and 1.97 (95% CI 1.49–2.60, p < 0.001), respectively. Conclusions: Administration of adjuvant chemotherapy is of particular benefit in patients with positive STSM following radical cystectomy for gross extravesical disease. Positive STSM may be a representative of “early metastatic” or micrometastatic disease. Full article
(This article belongs to the Special Issue Current and Future Bladder Cancer Landscape)
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13 pages, 1073 KiB  
Article
Assessment of the Ecological Association between Tobacco Smoking Exposure and Bladder Cancer Incidence over the Past Half-Century in the United States
by Thomas Seisen, Muhieddine Labban, Stuart R. Lipsitz, Mark A. Preston, Matthew Mossanen, Joaquim Bellmunt, Morgan Rouprêt, Toni K. Choueiri, Adam S. Kibel, Maxine Sun and Quoc-Dien Trinh
Curr. Oncol. 2023, 30(2), 1986-1998; https://doi.org/10.3390/curroncol30020154 - 6 Feb 2023
Cited by 2 | Viewed by 3303
Abstract
Background: Since tobacco smoking represents the most established risk factor for bladder cancer, we sought to assess the ecological association between tobacco smoking prevalence and bladder cancer incidence and to contrast it with lung cancer. Methods: The annual overall tobacco smoking prevalence rates [...] Read more.
Background: Since tobacco smoking represents the most established risk factor for bladder cancer, we sought to assess the ecological association between tobacco smoking prevalence and bladder cancer incidence and to contrast it with lung cancer. Methods: The annual overall tobacco smoking prevalence rates were extracted from the Report of the Surgeon General and the Center for Disease Control between 1953 and 1983. The overall age-adjusted incidence rates for bladder and lung cancers were derived from the Surveillance, Epidemiology, and End Results database between 1983 and 2013 (30-year latency period). Weighted least square regression models were used to assess bladder and lung cancer incidence rate differences (IRD) related to trends in tobacco smoking prevalence. A Wald test was used to compare whether the prevalence of tobacco smoking, as an explanatory variable, differentially predicts bladder versus lung cancer incidence rates. Results: The associations between tobacco smoking prevalence and bladder cancer incidence were not significant in the overall (IRD = +0.04; 95%CI (−0.14; +0.22); p = 0.63), male (IRD = +0.07; 95%CI (−0.09; +0.23); p = 0.37), or female (IRD = +0.12; 95%CI (−0.01; +0.25); p = 0.06) populations. There was an association between tobacco smoking prevalence and lung cancer incidence in the overall (IRD: +3.55; 95%CI ( +3.09; +4.00); p < 0.001), male (IRD: +4.82; 95%CI (+4.44; +5.20); p < 0.001), and female (IRD: +3.55; 95%CI (+3.12; +3.99); p < 0.001) populations. The difference between the observed associations of tobacco smoking prevalence with bladder versus lung cancer incidence was also significant in all examined populations (p < 0.001). Conclusions: Variations in tobacco smoking prevalence only partially explained the trends in the incidence of bladder cancer, indicating that its etiology is complex. Full article
(This article belongs to the Special Issue Current and Future Bladder Cancer Landscape)
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Review

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16 pages, 934 KiB  
Review
BCG and Alternative Therapies to BCG Therapy for Non-Muscle-Invasive Bladder Cancer
by Sarah Lidagoster, Reuben Ben-David, Benjamin De Leon and John P. Sfakianos
Curr. Oncol. 2024, 31(2), 1063-1078; https://doi.org/10.3390/curroncol31020079 - 16 Feb 2024
Cited by 3 | Viewed by 4650
Abstract
Bladder cancer is a heterogeneous disease. Treatment decisions are mostly decided based on disease stage (non-muscle invasive or muscle invasive). Patients with muscle-invasive disease will be offered a radical treatment combined with systemic therapy, while in those with non-muscle-invasive disease, an attempt to [...] Read more.
Bladder cancer is a heterogeneous disease. Treatment decisions are mostly decided based on disease stage (non-muscle invasive or muscle invasive). Patients with muscle-invasive disease will be offered a radical treatment combined with systemic therapy, while in those with non-muscle-invasive disease, an attempt to resect the tumor endoscopically will usually be followed by different intravesical instillations. The goal of intravesical therapy is to decrease the recurrence and/or progression of the tumor. In the current landscape of bladder cancer treatment, BCG is given intravesically to induce an inflammatory response and recruit immune cells to attack the malignant cells and induce immune memory. While the response to BCG treatment has changed the course of bladder cancer management and spared many “bladders”, some patients may develop BCG-unresponsive disease, leaving radical surgery as the best choice of curative treatment. As a result, a lot of effort has been put into identifying novel therapies like systemic pembrolizumab and Nadofaragene-Firadenovac to continue sparing bladders if BCG is ineffective. Moreover, recent logistic issues with BCG production caused a worldwide BCG shortage, re-sparking interest in alternative BCG treatments including mitomycin C, sequential gemcitabine with docetaxel, and others. This review encompasses both the historic and current role of BCG in the treatment of non-muscle-invasive bladder cancer, revisiting BCG alternative therapies and reviewing the novel therapeutics that were approved for the BCG-unresponsive stage or are under active investigation. Full article
(This article belongs to the Special Issue Current and Future Bladder Cancer Landscape)
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Other

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8 pages, 254 KiB  
Commentary
Immune Checkpoint Glycoproteins Have Polymorphism: Are Monoclonal Antibodies Too Specific?
by Mehrsa Jalalizadeh, Reza Yadollahvandmiandoab and Leonardo Oliveira Reis
Curr. Oncol. 2023, 30(1), 1267-1274; https://doi.org/10.3390/curroncol30010098 - 16 Jan 2023
Cited by 1 | Viewed by 2362
Abstract
Since the 2018 Nobel prize in medicine was granted to the discovery of immune escape by cancer cells, billions of dollars have been spent on a new form of cancer immunotherapy called immune checkpoint inhibition (ICI). In this treatment modality, monoclonal antibodies (mAbs) [...] Read more.
Since the 2018 Nobel prize in medicine was granted to the discovery of immune escape by cancer cells, billions of dollars have been spent on a new form of cancer immunotherapy called immune checkpoint inhibition (ICI). In this treatment modality, monoclonal antibodies (mAbs) are used to block cell-surface glycoproteins responsible for cancer immune escape. However, only a subset of patients benefit from this treatment. In this commentary, we focus on the polymorphism in the target molecules of these mAbs, namely PD-1, PD-L1 and CTLA4; we explain that using a single mAb from one clone is unlikely to succeed in treating all humans because humans have a genotype and phenotype polymorphism in these molecules. Monoclonal antibodies are highly specific and are capable of recognizing only one epitope (“monospecific”), which makes them ideal for use in laboratory animals because these animals are generationally inbred and genetically identical (isogenic). In humans, however, the encoding genes for PD-1, PD-L1 and CTLA4 have variations (alleles), and the final protein products have phenotype polymorphism. This means that small differences exist in these proteins among individual humans, rendering one mAb too specific to cover all patients. Our suggestion for the next step in advancing this oncotherapy is to focus on methods to tailor the mAb treatment individually for each patient or replace a single clone of mAb with less specific alternatives, e.g., a “cocktail of mAbs”, oligoclonal antibodies or recombinant polyclonal antibodies. Fortunately, there are ongoing clinical trials on oligoclonal antibodies at the moment. Full article
(This article belongs to the Special Issue Current and Future Bladder Cancer Landscape)
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