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Advances in Management of Bladder Cancer
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Advances in Management of Bladder Cancer

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Nephrology & Urology".

Deadline for manuscript submissions: closed (30 September 2021) | Viewed by 18031

Special Issue Editor

Prof. Marco Racioppi

E-Mail Website
Guest Editor
Department of Urology, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy
Interests: urologic oncology; bladder cancer; bladder cancer diagnosis; endoscopic surgery; oncological surgery; reconstructive surgery; radical cystectomy; orthotopic neobladder

Special Issue Information

Dear Colleagues,

Bladder cancer incidence is increasing worldwide. At present, 75% of cases are nonmuscle-invasive bladder cancer (NMIBC) and the rest are muscle-invasive (MIBC), which can also be a progression of the first kind. For this reason, the high prevalence in the population makes bladder cancer an important economic burden for health systems.

New advancements are required in the diagnostic setting in order to increase early diagnosis and to reduce the number of invasive procedures: Recent identification of target and potential biomarkers based on genomic sequencing analyses will be useful, also for predicting the response of novel therapeutic strategies.

High-risk NMIBC represents a clinical challenge, where gold standard treatment with BCG could fail with recurrence up to 55% and progression up to 20%. A better molecular characterization of the disease is required to define tailored protocols and to introduce new targeted therapies for NMIBC and also for MIBC. For the latter, new surgical techniques and different peri-operative protocols testing the role of PD-1/PD-L1 immune checkpoint inhibitors to combine systemic chemo-immunotherapy are under investigation with the aim of improving prognosis and reducing the impact of radical cystectomy on quality of life, moving forward personalized treatments.

This Special Issue will focus on improvements and criticisms regarding new advances in bladder cancer management.

Prof. Marco Racioppi
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 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. Journal of Clinical Medicine 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 2600 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

  • Bladder cancer
  • Diagnosis
  • Non-urothelial bladder cancer
  • Biomarkers
  • BCG
  • Endoscopic resection
  • Istopathology
  • Radical cystectomy
  • Chemo-Immunotherapy
  • Targeted therapy

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Published Papers (7 papers)

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Editorial

Jump to: Research, Review

3 pages, 153 KiB  
Editorial
Advances in Management of Bladder Cancer
by Marco Racioppi
J. Clin. Med. 2022, 11(1), 203; https://doi.org/10.3390/jcm11010203 - 30 Dec 2021
Cited by 7 | Viewed by 1532
Abstract
Bladder cancer (BC) is a complex disease with the following presentations, which are completely different from one another: non-muscle-infiltrating bladder cancer (NMIBC) and muscle-infiltrating bladder cancer (MIBC) [...] Full article
(This article belongs to the Special Issue Advances in Management of Bladder Cancer)

Research

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14 pages, 1665 KiB  
Article
Improved Non-Invasive Diagnosis of Bladder Cancer with an Electronic Nose: A Large Pilot Study
by PierFrancesco Bassi, Luca Di Gianfrancesco, Luigi Salmaso, Mauro Ragonese, Giuseppe Palermo, Emilio Sacco, Rosa Arboretti Giancristofaro, Riccardo Ceccato and Marco Racioppi
J. Clin. Med. 2021, 10(21), 4984; https://doi.org/10.3390/jcm10214984 - 27 Oct 2021
Cited by 13 | Viewed by 2242
Abstract
Background: Bladder cancer (BCa) emits specific volatile organic compounds (VOCs) in the urine headspace that can be detected by an electronic nose. The diagnostic performance of an electronic nose in detecting BCa was investigated in a pilot study. Methods: A prospective, single-center, controlled, [...] Read more.
Background: Bladder cancer (BCa) emits specific volatile organic compounds (VOCs) in the urine headspace that can be detected by an electronic nose. The diagnostic performance of an electronic nose in detecting BCa was investigated in a pilot study. Methods: A prospective, single-center, controlled, non-randomized, phase 2 study was carried out on 198 consecutive subjects (102 with proven BCa, 96 controls). Urine samples were evaluated with an electronic nose provided with 32 volatile gas analyzer sensors. The tests were repeated at least two times per sample. Accuracy, sensitivity, specificity, and variability were evaluated using mainly the non-parametric combination method, permutation tests, and discriminant analysis classification. Results: Statistically significant differences between BCa patients and controls were reported by 28 (87.5%) of the 32 sensors. The overall discriminatory power, sensitivity, and specificity were 78.8%, 74.1%, and 76%, respectively; 13/96 (13.5%) controls and 29/102 (28.4%) BCa patients were misclassified as false positive and false negative, respectively. Where the most efficient sensors were selected, the sensitivity and specificity increased up to 91.1% (72.5–100) and 89.1% (81–95.8), respectively. None of the tumor characteristics represented independent predictors of device responsiveness. Conclusions: The electronic nose might represent a potentially reliable, quick, accurate, and cost-effective tool for non-invasive BCa diagnosis. Full article
(This article belongs to the Special Issue Advances in Management of Bladder Cancer)
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10 pages, 992 KiB  
Article
The Influence of Lymph Node Count on Oncological Outcome of Radical Cystectomy in Chemotherapy Pre-Treated and Chemotherapy-Naïve Patients with Muscle Invasive Bladder Cancer
by Artur Lemiński, Krystian Kaczmarek, Wojciech Michalski, Bartosz Małkiewicz, Katarzyna Kotfis and Marcin Słojewski
J. Clin. Med. 2021, 10(21), 4923; https://doi.org/10.3390/jcm10214923 - 25 Oct 2021
Cited by 9 | Viewed by 2430
Abstract
Radical cystectomy (RC) with pelvic lymph node dissection (PLND) remains the mainstay of treatment for muscle-invasive bladder cancer (MIBC). The extent of PLND and number of removed lymph nodes (LNs) have been associated with improved staging and survival outcomes in several series of [...] Read more.
Radical cystectomy (RC) with pelvic lymph node dissection (PLND) remains the mainstay of treatment for muscle-invasive bladder cancer (MIBC). The extent of PLND and number of removed lymph nodes (LNs) have been associated with improved staging and survival outcomes in several series of RC patients. Neoadjuvant chemotherapy (NAC) has become standard of care for cisplatin-eligible patients qualified to RC, yet few studies on PLND stratified cases according to the receipt of NAC. We aimed to address this issue and reevaluate the prognostic value of PLND nodal yields in series of patients who underwent RC on the verge of the NAC era. This single-center, retrospective, clinical follow-up study enrolled 439 consecutive patients, out of whom 83 received NAC. We analyzed survival outcome of RC according to the number of removed nodes between NAC and non-NAC subgroups. We found PLND thresholds of 10 and 15 LNs prognostically meaningful in our study cohort, and this association was particularly pronounced in the non-NAC subgroup. Higher numbers of LNs provided a 25% reduction in risk of all-cause mortality and correspondingly correlated with up to a 14% increase in 3-year overall survival. The receipt of NAC diminished the benefit of adequate PLND, as the number of retrieved LNs was not associated with survival in the NAC-RC cohort. Given the limitations of our study, additional research is needed to verify these findings. Full article
(This article belongs to the Special Issue Advances in Management of Bladder Cancer)
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10 pages, 8581 KiB  
Article
Intravesical Prostatic Protrusion and Prognosis of Non-Muscle Invasive Bladder Cancer: Analysis of Long-Term Data over 5 Years with Machine-Learning Algorithms
by Junghoon Lee, Min Soo Choo, Sangjun Yoo, Min Chul Cho, Hwancheol Son and Hyeon Jeong
J. Clin. Med. 2021, 10(18), 4263; https://doi.org/10.3390/jcm10184263 - 20 Sep 2021
Cited by 5 | Viewed by 2925
Abstract
We aim to investigate the significance of intravesical prostate protrusion (IPP) on the prognosis of non-muscle invasive bladder cancer (NMIBC) after the transurethral resection of bladder tumors (TURBT). For newly diagnosed NMIBC, we retrospectively analyzed the association between prognosis and IPP for at [...] Read more.
We aim to investigate the significance of intravesical prostate protrusion (IPP) on the prognosis of non-muscle invasive bladder cancer (NMIBC) after the transurethral resection of bladder tumors (TURBT). For newly diagnosed NMIBC, we retrospectively analyzed the association between prognosis and IPP for at least a 5-year follow-up. A degree of IPP over 5 mm in a preoperative CT scan was classified as severe. The primary endpoint was recurrence-free survival, and the secondary endpoint was progression-free survival. The machine learning (ML) algorithm of a support vector machine was used for predictive model development. Of a total of 122 patients, ultimately, severe IPP was observed in 33 patients (27.0%). IPP correlated positively with age, BPH, recurrence, and prognosis. Severe IPP was significantly higher in the recurrence group and reduced in the recurrence-free survival group (p = 0.038, p = 0.032). Severe IPP independently increased the risk of intravesical recurrence by 2.6 times. The addition of IPP to the known oncological risk factors in the prediction model using the ML algorithm improved the predictability of cancer recurrence by approximately 6%, to 0.803. IPP was analyzed as a potential independent risk factor for NMIBC recurrence and progression after TURBT. This anatomical feature of the prostate could affect the recurrence of bladder tumors. Full article
(This article belongs to the Special Issue Advances in Management of Bladder Cancer)
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14 pages, 2635 KiB  
Article
Expression of ADAM Proteases in Bladder Cancer Patients with BCG Failure: A Pilot Study
by Renate Pichler, Andrea Katharina Lindner, Georg Schäfer, Gennadi Tulchiner, Nina Staudacher, Martin Mayr, Eva Comperat, Jacob J. Orme, Gert Schachtner and Martin Thurnher
J. Clin. Med. 2021, 10(4), 764; https://doi.org/10.3390/jcm10040764 - 14 Feb 2021
Cited by 5 | Viewed by 2773
Abstract
Although Bacillus Calmette Guérin (BCG) remains a mainstay of adjuvant treatment in high-risk, non-muscle-invasive bladder cancer, BCG failure occurs in up to 40% of patients, with radical cystectomy (RC) as the inevitable therapeutic consequence. Current data suggest that PD-L1 immunosuppressive signaling is responsible [...] Read more.
Although Bacillus Calmette Guérin (BCG) remains a mainstay of adjuvant treatment in high-risk, non-muscle-invasive bladder cancer, BCG failure occurs in up to 40% of patients, with radical cystectomy (RC) as the inevitable therapeutic consequence. Current data suggest that PD-L1 immunosuppressive signaling is responsible for BCG failure, supporting the therapeutic rationale of combining checkpoint inhibitors with BCG. To address the immune cascade in 19 RC specimens obtained after BCG failure, we applied a small immunohistochemical (IHC) panel consisting of selected markers (PD-L1, GATA-3, a disintegrin and metalloproteinase (ADAM) proteases, IL-10/IL-10R). A modified quick score was used for IHC semi-quantification of these markers in tumor cells (TC) and immune cells (IC) within two different regions: muscle-invasive bladder cancer (MIBC) and primary/concurrent carcinoma in situ (CIS). Contrary to expectation, PD-L1 was consistently low, irrespective of tumor region and cell type. Intriguingly, expression of ADAM17, which has been reported to release membrane-bound PD-L1, was high in both tumor regions and cell types. Moreover, expression of GATA3, IL-10, and IL-10R was also increased, indicative of a generally immunosuppressive tumor microenvironment in BCG failure. ADAM10 expression was associated with advanced tumor disease at RC. Our findings raise the possibility that ADAM proteases may cleave PD-L1 from the surface of bladder TC and possibly also from IC. Therefore, IHC assessment of PD-L1 expression seems to be insufficient and should be supplemented by ADAM10/17 in patients with BCG failure. Full article
(This article belongs to the Special Issue Advances in Management of Bladder Cancer)
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13 pages, 1216 KiB  
Article
Comparison of a Significant Decline in the Glomerular Filtration Rate between Ileal Conduit and Ileal Neobladder Urinary Diversions after Radical Cystectomy: A Propensity Score-Matched Analysis
by Jihion Yu, Bumsik Hong, Jun-Young Park, Yongsoo Lee, Jai-Hyun Hwang, Yu-Gyeong Kong and Young-Kug Kim
J. Clin. Med. 2020, 9(7), 2236; https://doi.org/10.3390/jcm9072236 - 14 Jul 2020
Cited by 13 | Viewed by 3128
Abstract
Urinary diversion after radical cystectomy is associated with a risk of renal function impairment. A significant decline in the glomerular filtration rate (GFR) (i.e., a ≥30% decline in baseline GFR after 12 months) is associated with long-term renal function impairment. We compared the [...] Read more.
Urinary diversion after radical cystectomy is associated with a risk of renal function impairment. A significant decline in the glomerular filtration rate (GFR) (i.e., a ≥30% decline in baseline GFR after 12 months) is associated with long-term renal function impairment. We compared the significant GFR decline between ileal conduit and ileal neobladder urinary diversions 12 months after radical cystectomy. We retrospectively included radical cystectomy patients. Propensity score-matched analysis was performed. The primary outcome was the incidence of a significant GFR decline in ileal conduit urinary diversion (ileal conduit group) and ileal neobladder urinary diversion (ileal neobladder group) 12 months after radical cystectomy. The secondary outcomes were the change of GFR and the incidence of end-stage renal disease (ESRD) in the two groups. After propensity score matching, the ileal conduit and neobladder groups had 117 patients each. The incidence of a significant GFR decline was not significantly different between ileal conduit and ileal neobladder groups (12.0% vs. 13.7%, p = 0.845). The change of GFR and ESRD incidence were not significantly different between the two groups (−8.4% vs. −9.7%, p = 0.480; 4.3% vs. 5.1%, p > 0.999, respectively). These results can provide important information on appropriate selection of the urinary diversion type in radical cystectomy. Full article
(This article belongs to the Special Issue Advances in Management of Bladder Cancer)
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Review

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8 pages, 199 KiB  
Review
Quality of Life in Female Patients Following Ileal Neobladder and Ileal Conduit: Where Are We?
by Salvatore Siracusano, Agustina Zaka, Federico Romantini, Antonio Benito Porcaro, Carlo Vicentini and Cristina Lonardi
J. Clin. Med. 2021, 10(14), 3042; https://doi.org/10.3390/jcm10143042 - 8 Jul 2021
Cited by 9 | Viewed by 1930
Abstract
Women undergoing a radical cystectomy (RC) followed by a urinary diversion (UD) for bladder cancer (BC), experience a substantial reduction in health-related quality of life (HRQOL). At present, studies comparing long-term QOL outcomes for different UD methods in female patients are lacking. We [...] Read more.
Women undergoing a radical cystectomy (RC) followed by a urinary diversion (UD) for bladder cancer (BC), experience a substantial reduction in health-related quality of life (HRQOL). At present, studies comparing long-term QOL outcomes for different UD methods in female patients are lacking. We summarize the current state of the QoL assessment in female patients after an RC. Full article
(This article belongs to the Special Issue Advances in Management of Bladder Cancer)
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