Cancers

Research

16 pages, 3428 KiB

Open AccessArticle

Development of Traceable Mouse Models of Advanced and Metastatic Bladder Cancer

by Emma Desponds, Konstantina Kioseoglou, Hana Zdimerova, Marco Ongaro, Grégory Verdeil and Marine M. Leblond

Cancers 2024, 16(12), 2245; https://doi.org/10.3390/cancers16122245 - 17 Jun 2024

Viewed by 1125

Abstract

Bladder cancer (BC) is the fourth most common cancer in men, with a poor patient prognosis for advanced disease. The poor survival of patients with muscle-invasive bladder cancer (MIBC) and metastatic status emphasizes the urgent need to develop new therapies. Lacking in the [...] Read more.

Bladder cancer (BC) is the fourth most common cancer in men, with a poor patient prognosis for advanced disease. The poor survival of patients with muscle-invasive bladder cancer (MIBC) and metastatic status emphasizes the urgent need to develop new therapies. Lacking in the field of BC is the availability of relevant advanced BC mouse models, especially metastatic ones, that accurately recapitulate the complexities of human pathology to test and study new therapeutic strategies. Addressing this need, we developed a traceable mouse model of BC that expresses tumor-associated antigens within the context of advanced muscle-invasive BC. This novel system was achieved through the deletion of the tp53 and pten genes, alongside the incorporation of the fusion construct of Firefly luciferase (Luc) and the SIYRYYGL (SIY) T-cell antigen. We validate that the presence of the transgene did not impact on the development of the tumors while allowing us to measure tumor progression by bioluminescence. We show that the transgene did not influence the composition of the immune tumor microenvironment. More importantly, we report that this model was unresponsive to anti-PD-1 treatment, as in the majority of patients with BC. We also develop a new model based on the orthotopic injection of BC clonal cell lines derived from our first model. We demonstrate that this new model invades the muscle layer and has a metastasis development rate of 83%. The advantage of this model is that we can visualize tumor growth and metastasis development in vivo. These mouse models’ characteristics, displaying many similarities with the human pathology, provide a valuable tool for tracking tumor progression, metastasis spread in vivo, and treatment resistance, as well as exploring fundamental and translational aspects of BC biology. This work contributes to the improvement in the landscape of mouse models of advanced BC for testing new therapeutic strategies. Full article

(This article belongs to the Special Issue New Insights into Urologic Oncology)

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11 pages, 571 KiB

Open AccessArticle

Low Alanine Aminotransferase as a Marker for Sarcopenia and Frailty, Is Associated with Decreased Survival of Bladder Cancer Patients and Survivors—A Retrospective Data Analysis of 3075 Patients

by Menachem Laufer, Maxim Perelman, Gad Segal, Michal Sarfaty and Edward Itelman

Cancers 2024, 16(1), 174; https://doi.org/10.3390/cancers16010174 - 29 Dec 2023

Cited by 3 | Viewed by 1319

Abstract

Background. Sarcopenia is characterized by the loss of muscle mass and function and is associated with frailty, a syndrome linked to an increased likelihood of falls, fractures, and physical disability. Both frailty and sarcopenia are recognized as markers for shortened survival in a [...] Read more.

Background. Sarcopenia is characterized by the loss of muscle mass and function and is associated with frailty, a syndrome linked to an increased likelihood of falls, fractures, and physical disability. Both frailty and sarcopenia are recognized as markers for shortened survival in a number of medical conditions and in cancer patient populations. Low alanine aminotransferase (ALT) values, representing low muscle mass (sarcopenia), may be associated with increased frailty and subsequently shortened survival in cancer patients. In the current study, we aimed to assess the potential relationship between low ALT and shorter survival in bladder cancer patients and survivors. Patients and Methods. This was a retrospective analysis of bladder cancer patients and survivors, both in and outpatients. We defined patients with sarcopenia as those presenting with ALT < 17 IU/L. Results. A total of 5769 bladder cancer patients’ records were identified. After the exclusion of patients with no available ALT values or ALT levels above the upper normal limit, the final study cohort included 3075 patients (mean age 73.2 ± 12 years), of whom 80% were men and 1362 (53% had ALT ≤ 17 IU/L. The mean ALT value of patients within the low ALT group was 11.44 IU/L, while the mean value in the higher ALT level group was 24.32 IU/L (p < 0.001). Patients in the lower ALT group were older (74.7 vs. 71.4 years; p < 0.001), had lower BMI (25.8 vs. 27; p < 0.001), and their hemoglobin values were lower (11.7 vs. 12.6 g/dL; p < 0.001). In a univariate analysis, low ALT levels were associated with a 45% increase in mortality (95% CI 1.31–1.60, p < 0.001). In a multivariate model controlling for age, kidney function, and hemoglobin, low ALT levels were still associated with 22% increased mortality. Conclusions. Low ALT values, indicative of sarcopenia and frailty, are associated with decreased survival of bladder cancer patients and survivors and could potentially be applied for optimizing individual treatment decisions. Full article

(This article belongs to the Special Issue New Insights into Urologic Oncology)

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Review

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14 pages, 1363 KiB

Open AccessReview

Striving for Equity: Examining Health Disparities in Urologic Oncology

by Dhruv Puri, Kshitij Pandit, Noah Choi, Brent S. Rose, Rana R. McKay and Aditya Bagrodia

Cancers 2024, 16(21), 3559; https://doi.org/10.3390/cancers16213559 - 22 Oct 2024

Viewed by 527

Abstract

Health disparities in urologic oncology, particularly in prostate, bladder, kidney, and testicular cancers, significantly impact patient outcomes across different demographic groups. This narrative review aims to investigate the extent and drivers of these disparities, focusing on the influence of race, socioeconomic status, and [...] Read more.

Health disparities in urologic oncology, particularly in prostate, bladder, kidney, and testicular cancers, significantly impact patient outcomes across different demographic groups. This narrative review aims to investigate the extent and drivers of these disparities, focusing on the influence of race, socioeconomic status, and geographic location on diagnosis, treatment, and survival outcomes. We conducted a comprehensive review of the existing literature and analyzed data from national cancer databases to identify patterns of inequity. Our findings reveal that minority populations, individuals with lower socioeconomic status, and those residing in underserved areas are less likely to receive timely and guideline-based care, leading to worse outcomes. This review underscores the urgent need for targeted interventions, including policy reforms, health system restructuring, enhanced community outreach, and increased funding for disparity-focused research, to ensure equitable access to high-quality oncologic care. Addressing these disparities is crucial for improving cancer outcomes and achieving health equity in urologic oncology. Full article

(This article belongs to the Special Issue New Insights into Urologic Oncology)

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18 pages, 1058 KiB

Open AccessReview

Developmental Therapeutics in Metastatic Prostate Cancer: New Targets and New Strategies

by Jingsong Zhang and Juskaran S. Chadha

Cancers 2024, 16(17), 3098; https://doi.org/10.3390/cancers16173098 - 6 Sep 2024

Viewed by 1386

Abstract

There is an unmet need to develop new treatments for metastatic prostate cancer. With the development of targeted radioligand therapies, bispecific T cell engagers, antibody–drug conjugates and chimeric antigen receptor T cell (CAR T) therapies, tumor-associated cell surface antigens have emerged as new [...] Read more.

There is an unmet need to develop new treatments for metastatic prostate cancer. With the development of targeted radioligand therapies, bispecific T cell engagers, antibody–drug conjugates and chimeric antigen receptor T cell (CAR T) therapies, tumor-associated cell surface antigens have emerged as new therapeutic targets in metastatic prostate cancer. Ongoing and completed clinical trials targeting prostate-specific membrane antigen (PSMA), six transmembrane epithelial antigens of the prostate 1 (STEAP1), kallikrein-related peptidase 2 (KLK2), prostate stem cell antigen (PSCA), and delta-like protein 3 (DLL3) in metastatic prostate cancer were reviewed. Strategies for sequential or combinational therapy were discussed. Full article

(This article belongs to the Special Issue New Insights into Urologic Oncology)

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13 pages, 302 KiB

Open AccessReview

Is There an Opportunity to De-Escalate Treatments in Selected Patients with Metastatic Hormone-Sensitive Prostate Cancer?

by María Antonia Gómez-Aparicio, Fernando López-Campos, David Buchser, Antonio Lazo, Patricia Willisch, Abrahams Ocanto, Paul Sargos, Mohamed Shelan and Felipe Couñago

Cancers 2024, 16(13), 2331; https://doi.org/10.3390/cancers16132331 - 26 Jun 2024

Viewed by 2380

Abstract

The treatment landscape for metastatic hormone-sensitive prostate cancer continues to evolve, with systemic treatment being the mainstay of current treatment. Prognostic and predictive factors such as tumour volume and disease presentation have been studied to assess responses to different treatments. Intensification and de-escalation [...] Read more.

The treatment landscape for metastatic hormone-sensitive prostate cancer continues to evolve, with systemic treatment being the mainstay of current treatment. Prognostic and predictive factors such as tumour volume and disease presentation have been studied to assess responses to different treatments. Intensification and de-escalation strategies arouse great interest, so several trials are being developed to further personalize the therapy in these populations. Is there an optimal sequence and a possible option to de-intensify treatment in selected patients with a favourable profile? This and other goals will be the subject of this review. Full article

(This article belongs to the Special Issue New Insights into Urologic Oncology)

14 pages, 1855 KiB

Open AccessReview

Diagnostic Biomarkers in Renal Cell Tumors According to the Latest WHO Classification: A Focus on Selected New Entities

by Francesca Sanguedolce, Roberta Mazzucchelli, Ugo Giovanni Falagario, Angelo Cormio, Magda Zanelli, Andrea Palicelli, Maurizio Zizzo, Albino Eccher, Matteo Brunelli, Andrea Benedetto Galosi, Giuseppe Carrieri and Luigi Cormio

Cancers 2024, 16(10), 1856; https://doi.org/10.3390/cancers16101856 - 13 May 2024

Cited by 1 | Viewed by 1774

Abstract

The fifth edition of the World Health Organization (WHO) classification for urogenital tumors, released in 2022, introduces some novelties in the chapter on renal epithelial tumors compared to the previous 2016 classification. Significant changes include the recognition of new disease entities and adjustments [...] Read more.

The fifth edition of the World Health Organization (WHO) classification for urogenital tumors, released in 2022, introduces some novelties in the chapter on renal epithelial tumors compared to the previous 2016 classification. Significant changes include the recognition of new disease entities and adjustments in the nomenclature for certain pathologies. Notably, each tumor entity now includes minimum essential and desirable criteria for reliable diagnosis. This classification highlights the importance of biological and molecular characterization alongside traditional cytological and architectural features. In this view, immunophenotyping through immunohistochemistry (IHC) plays a crucial role in bridging morphology and genetics. This article aims to present and discuss the role of key immunohistochemical markers that support the diagnosis of new entities recognized in the WHO classification, focusing on critical topics associated with single markers, in the context of specific tumors, such as the clear cell capillary renal cell tumor (CCPRCT), eosinophilic solid and cystic renal cell carcinoma (ESC-RCC), and so-called “other oncocytic tumors”, namely the eosinophilic vacuolated tumor (EVT) and low-grade oncocytic tumor (LOT). Their distinctive characteristics and immunophenotypic profiles, along with insights regarding diagnostic challenges and the differential diagnosis of these tumors, are provided. This state-of-the-art review offers valuable insights in biomarkers associated with novel renal tumors, as well as a tool to implement diagnostic strategies in routine practice. Full article

(This article belongs to the Special Issue New Insights into Urologic Oncology)

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Other

Jump to: Research, Review

37 pages, 5146 KiB

Open AccessSystematic Review

Application of Geographic Information Systems (GIS) in the Study of Prostate Cancer Disparities: A Systematic Review

by Christiane J. El Khoury

Cancers 2024, 16(15), 2715; https://doi.org/10.3390/cancers16152715 - 30 Jul 2024

Viewed by 1101

Abstract

Introduction: PCa is one of the cancers that exhibits the widest disparity gaps. Geographical place of residence has been shown to be associated with healthcare access/utilization and PCa outcomes. Geographical Information Systems (GIS) are widely being utilized for PCa disparities research, however, [...] Read more.

Introduction: PCa is one of the cancers that exhibits the widest disparity gaps. Geographical place of residence has been shown to be associated with healthcare access/utilization and PCa outcomes. Geographical Information Systems (GIS) are widely being utilized for PCa disparities research, however, inconsistencies in their application exist. This systematic review will summarize GIS application within PCa disparities research, highlight gaps in the literature, and propose alternative approaches. Methods: This paper followed the methods of the Cochrane Collaboration and the criteria set of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Articles published in peer-reviewed journals were searched through the PubMed, Embase, and Web of Science databases until December 2022. The main inclusion criteria were employing a GIS approach and examining a relationship between geographical components and PCa disparities. The main exclusion criteria were studies conducted outside the US and those that were not published in English. Results: A total of 25 articles were included; 23 focused on PCa measures as outcomes: incidence, survival, and mortality, while only 2 examined PCa management. GIS application in PCa disparities research was grouped into three main categories: mapping, processing, and analysis. GIS mapping allowed for the visualization of quantitative, qualitative, and temporal trends of PCa factors. GIS processing was mainly used for geocoding and smoothing of PCa rates. GIS analysis mainly served to evaluate global spatial autocorrelation and distribution of PCa cases, while local cluster identification techniques were mainly employed to identify locations with poorer PCa outcomes, soliciting public health interventions. Discussion: Varied GIS applications and methodologies have been used in researching PCa disparities. Multiple geographical scales were adopted, leading to variations in associations and outcomes. Geocoding quality varied considerably, leading to less robust findings. Limitations in cluster-detection approaches were identified, especially when variations were captured using the Spatial Scan Statistic. GIS approaches utilized in other diseases might be applied within PCa disparities research for more accurate inferences. A novel approach for GIS research in PCa disparities could be focusing more on geospatial disparities in procedure utilization especially when it comes to PCa screening techniques. Conclusions: This systematic review summarized and described the current state and trend of GIS application in PCa disparities research. Although GIS is of crucial importance when it comes to PCa disparities research, future studies should rely on more robust GIS techniques, carefully select the geographical scale studied, and partner with GIS scientists for more accurate inferences. Such interdisciplinary approaches have the potential to bridge the gaps between GIS and cancer prevention and control to further advance cancer equity. Full article

(This article belongs to the Special Issue New Insights into Urologic Oncology)

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16 pages, 2877 KiB

Open AccessSystematic Review

Urine-Based Biomarker Test Uromonitor^® in the Detection and Disease Monitoring of Non-Muscle-Invasive Bladder Cancer—A Systematic Review and Meta-Analysis of Diagnostic Test Performance

by Anton P. Kravchuk, Ingmar Wolff, Christian Gilfrich, Ralph M. Wirtz, Paula Soares, Kay-Patrick Braun, Sabine D. Brookman-May, Lisa Kollitsch, Katharina Hauner, Martin Burchardt, Johannes Bründl, Maximilian Burger and Matthias May

Cancers 2024, 16(4), 753; https://doi.org/10.3390/cancers16040753 - 11 Feb 2024

Cited by 1 | Viewed by 2075

Abstract

Optimal urine-based diagnostic tests (UBDT) minimize unnecessary follow-up cystoscopies in patients with non-muscle-invasive bladder-cancer (NMIBC), while accurately detecting high-grade bladder-cancer without false-negative results. Such UBDTs have not been comprehensively described upon a broad, validated dataset, resulting in cautious guideline recommendations. Uromonitor^®, [...] Read more.

Optimal urine-based diagnostic tests (UBDT) minimize unnecessary follow-up cystoscopies in patients with non-muscle-invasive bladder-cancer (NMIBC), while accurately detecting high-grade bladder-cancer without false-negative results. Such UBDTs have not been comprehensively described upon a broad, validated dataset, resulting in cautious guideline recommendations. Uromonitor^®, a urine-based DNA-assay detecting hotspot alterations in TERT, FGFR3, and KRAS, shows promising initial results. However, a systematic review merging all available data is lacking. Studies investigating the diagnostic performance of Uromonitor^® in NMIBC until November 2023 were identified in PubMed, Embase, Web-of-Science, Cochrane, Scopus, and medRxiv databases. Within aggregated analyses, test performance and area under the curve/AUC were calculated. This project fully implemented the PRISMA statement. Four qualifying studies comprised a total of 1190 urinary tests (bladder-cancer prevalence: 14.9%). Based on comprehensive analyses, sensitivity, specificity, positive-predictive value/PPV, negative-predictive value/NPV, and test accuracy of Uromonitor^® were 80.2%, 96.9%, 82.1%, 96.6%, and 94.5%, respectively, with an AUC of 0.886 (95%-CI: 0.851–0.921). In a meta-analysis of two studies comparing test performance with urinary cytology, Uromonitor^® significantly outperformed urinary cytology in sensitivity, PPV, and test accuracy, while no significant differences were observed for specificity and NPV. This systematic review supports the use of Uromonitor^® considering its favorable diagnostic performance. In a cohort of 1000 patients with a bladder-cancer prevalence of ~15%, this UBDT would avert 825 unnecessary cystoscopies (true-negatives) while missing 30 bladder-cancer cases (false-negatives). Due to currently limited aggregated data from only four studies with heterogeneous quality, confirmatory studies are needed. Full article

(This article belongs to the Special Issue New Insights into Urologic Oncology)

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