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Time for a Paradigm Shift in Non-muscle Invasive Bladder Cancer

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

Deadline for manuscript submissions: closed (15 May 2022) | Viewed by 8563

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Special Issue Editor

Prof. Dr. Jørgen Bjerggaard Jensen

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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,

Non-Muscle Invasive Bladder Cancer (NMIBC) is a vary 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 is treated by radical cystectomy. However, despite this variety of treatment modalities that have optimized slightly over the last few decades, a recurrence rate of more than 50% of all patients highlights the urgent need for a more optimal treatment up front. Moreover, piecemeal TURBT in NMIBC that violates normal oncological principles and life-long follow-up regimens based on traditional pathology risk stratification in a disease where biomarkers have been studied for decades calls for a change.

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

Prof. Jørgen Bjerggaard Jensen
Guest Editor

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Keywords

non-muscle invasive bladder cancer
treatment
instillation
follow-up

Published Papers (3 papers)

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Research

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11 pages, 1404 KiB

Open AccessArticle

Compared Efficacy of Adjuvant Intravesical BCG-TICE vs. BCG-RIVM for High-Risk Non-Muscle Invasive Bladder Cancer (NMIBC): A Propensity Score Matched Analysis

by Francesco Del Giudice, Rocco Simone Flammia, Benjamin I. Chung, Marco Moschini, Benjamin Pradere, Andrea Mari, Francesco Soria, Simone Albisinni, Wojciech Krajewski, Tomasz Szydełko, Ekaterina Laukhtina, David D’Andrea, Andrea Gallioli, Laura S. Mertens, Martina Maggi, Alessandro Sciarra, Stefano Salciccia, Matteo Ferro, Carlo Maria Scornajenghi, Vincenzo Asero, Susanna Cattarino, Mario De Angelis, Giovanni E. Cacciamani, Riccardo Autorino, Savio Domenico Pandolfo, Ugo Giovanni Falagario, Nicola D’Altilia, Vito Mancini, Marco Chirico, Francesco Cinelli, Carlo Bettocchi, Luigi Cormio, Giuseppe Carrieri, Ettore De Berardinis, Gian Maria Busetto and on behalf of European Association of Urology (EAU)—Young Academic Urologists (YAU) Urothelial Cancer Working Party Show full author list Hide full author list

Cancers 2022, 14(4), 887; https://doi.org/10.3390/cancers14040887 - 10 Feb 2022

Cited by 12 | Viewed by 2982

Abstract

Background: Intravesical immunotherapy with bacillus Calmette–Guerin (BCG) is the standard therapy for high-risk non-muscle invasive bladder cancer (NMIBC). The superiority of any BCG strain over another could not be demonstrated yet. Methods: Patients with NMIBCs underwent adjuvant induction ± maintenance schedule of intravesical immunotherapy with either BCG TICE or RIVM at two high-volume tertiary institutions. Only BCG-naïve patients and those treated with the same strain over the course of follow-up were included. One-to-one (1:1) propensity score matching (PSM) between the two cohorts was utilized to adjust for baseline demographic and tumor characteristics imbalances. Kaplan–Meier estimates and multivariable Cox regression models according to high-risk NMIBC prognostic factors were implemented to address survival differences between the strains. Sub-group analysis modeling of the influence of routine secondary resection (re-TUR) in the setting of the sole maintenance adjuvant schedule for the two strains was further performed. Results: 852 Ta-T1 NMIBCs (n = 719, 84.4% on TICE; n = 133, 15.6% on RIVM) with a median of 53 (24–77) months of follow-up were reviewed. After PSM, no differences at 5-years RFS, PFS, and CSS at both Kaplan–Meier and Cox regression analyses were detected for the whole cohort. In the sub-group setting of full adherence to European/American Urology Guidelines (EAU/NCCN), BCG TICE demonstrated longer 5-years RFS compared to RIVM (68% vs. 43%, p = 0.008; HR: 0.45 95% CI 0.25–0.81). Conclusion: When routinely performing re-TUR followed by a maintenance BCG schedule, TICE was superior to RIVM for RFS outcomes. However, no significant differences were detected for PFS and CSS, respectively. Full article

(This article belongs to the Special Issue Time for a Paradigm Shift in Non-muscle Invasive Bladder Cancer)

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17 pages, 3190 KiB

Open AccessArticle

DNA Methylome Changes of Muscle- and Neuronal-Related Processes Precede Bladder Cancer Invasiveness

by Maria Bošković, Blanka Roje, Felicia Fei-Lei Chung, Andrea Gelemanović, Vincent Cahais, Cyrille Cuenin, Rita Khoueiry, Katarina Vilović, Zdenko Herceg and Janoš Terzić

Cancers 2022, 14(3), 487; https://doi.org/10.3390/cancers14030487 - 19 Jan 2022

Cited by 2 | Viewed by 2509

Abstract

Bladder cancer (BC) is the ninth leading cause of cancer death with one of the highest recurrence rates among all cancers. One of the main risks for BC development is exposure to nitrosamines present in tobacco smoke or in other products. Aberrant epigenetic (DNA methylation) changes accompanied by deregulated gene expression are an important element of cancer pathogenesis. Therefore, we aimed to determine DNA methylation signatures and their impacts on gene expression in mice treated with N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN), a carcinogen similar to compounds found in tobacco smoke. Following BBN administration mice developed non-invasive or invasive bladder cancers. Surprisingly, muscle- and neuronal-related pathways emerged as the most affected in those tumors. Hypo- and hypermethylation changes were present within non-invasive BC, across CpGs mapping to the genes involved in muscle- and neuronal-related pathways, however, methylation differences were not sufficient to affect the expression of the majority of associated genes. Conversely, invasive tumors displayed hypermethylation changes that were linked with alterations in gene expression profiles. Together, these findings indicate that bladder cancer progression could be revealed through methylation profiling at the pre-invasive cancer stage that could assist monitoring of cancer patients and guide novel therapeutic approaches. Full article

(This article belongs to the Special Issue Time for a Paradigm Shift in Non-muscle Invasive Bladder Cancer)

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Other

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25 pages, 2193 KiB

Open AccessSystematic Review

Efficacy of Different Bacillus of Calmette-Guérin (BCG) Strains on Recurrence Rates among Intermediate/High-Risk Non-Muscle Invasive Bladder Cancers (NMIBCs): Single-Arm Study Systematic Review, Cumulative and Network Meta-Analysis

by Francesco Del Giudice, Vincenzo Asero, Eugenio Bologna, Carlo Maria Scornajenghi, Dalila Carino, Virginia Dolci, Pietro Viscuso, Stefano Salciccia, Alessandro Sciarra, David D’Andrea, Benjamin Pradere, Marco Moschini, Andrea Mari, Simone Albisinni, Wojciech Krajewski, Tomasz Szydełko, Bartosz Małkiewicz, Łukasz Nowak, Ekaterina Laukhtina, Andrea Gallioli, Laura S. Mertens, Gautier Marcq, Alessia Cimadamore, Luca Afferi, Francesco Soria, Keiichiro Mori, Karl Heinrich Tully, Renate Pichler, Matteo Ferro, Octavian Sabin Tataru, Riccardo Autorino, Simone Crivellaro, Felice Crocetto, Gian Maria Busetto, Satvir Basran, Michael L. Eisenberg, Benjamin Inbeh Chung and Ettore De Berardinis Show full author list Hide full author list

Cancers 2023, 15(7), 1937; https://doi.org/10.3390/cancers15071937 - 23 Mar 2023

Cited by 5 | Viewed by 2343

Abstract

Background: In an era of Bacillus of Calmette-Guérin (BCG) shortages, the comparative efficacy from different adjuvant intravesical BCG strains in non-muscle invasive bladder cancer (NMIBC) has not been clearly elucidated. We aim to compare, through a systematic review and meta-analysis, the cumulative BC recurrence rates and the best efficacy profile of worldwide available BCG strains over the last forty years. Methods: PubMed, Scopus, Web of Science, Embase, and Cochrane databases were searched from 1982 up to 2022. A meta-analysis of pooled BC recurrence rates was stratified for studies with ≤3-y vs. >3-y recurrence-free survival (RFS) endpoints and the strain of BCG. Sensitivity analysis, sub-group analysis, and meta-regression were implemented to investigate the contribution of moderators to heterogeneity. A random-effect network meta-analysis was performed to compare BCG strains on a multi-treatment level. Results: In total, n = 62 series with n = 15,412 patients in n = 100 study arms and n = 10 different BCG strains were reviewed. BCG Tokyo 172 exhibited the lowest pooled BC recurrence rate among studies with ≤3-y RFS (0.22 (95%CI 0.16–0.28). No clinically relevant difference was noted among strains at >3-y RFS outcomes. Sub-group and meta-regression analyses highlighted the influence of NMIBC risk-group classification and previous intravesical treated categories. Out of the n = 11 studies with n = 7 BCG strains included in the network, BCG RIVM, Tice, and Tokyo 172 presented with the best-predicted probability for efficacy, yet no single strain was significantly superior to another in preventing BC recurrence risk. Conclusion: We did not identify a BCG stain providing a clinically significant lower BC recurrence rate. While these findings might discourage investment in future head-to-head randomized comparison, we were, however, able to highlight some potential enhanced benefits from the genetically different BCG RIVM, Tice, and Tokyo 172. This evidence would support the use of such strains for future BCG trials in NMIBCs. Full article

(This article belongs to the Special Issue Time for a Paradigm Shift in Non-muscle Invasive Bladder Cancer)

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