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Search Results (2,140)

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18 pages, 1890 KiB  
Systematic Review
Diagnostic Performance and Interobserver Agreement of the Vesical Imaging–Reporting and Data System (VI-RADS) in Bladder Cancer Staging: A Systematic Review
by Alexandru Nesiu, Dorin Novacescu, Silviu Latcu, Razvan Bardan, Alin Cumpanas, Flavia Zara, Victor Buciu, Radu Caprariu, Talida Georgiana Cut and Ademir Horia Stana
Medicina 2025, 61(3), 469; https://doi.org/10.3390/medicina61030469 - 7 Mar 2025
Viewed by 187
Abstract
Background and Objectives: The Vesical Imaging–Reporting and Data System (VI-RADS) represents a standardized approach for interpreting multiparametric magnetic resonance imaging (mp-MRI) in bladder cancer (BC) evaluation. This systematic review aimed to assess the VI-RADS’ diagnostic performance and interobserver agreement in distinguishing muscle-invasive [...] Read more.
Background and Objectives: The Vesical Imaging–Reporting and Data System (VI-RADS) represents a standardized approach for interpreting multiparametric magnetic resonance imaging (mp-MRI) in bladder cancer (BC) evaluation. This systematic review aimed to assess the VI-RADS’ diagnostic performance and interobserver agreement in distinguishing muscle-invasive from non-muscle-invasive BC, a crucial differentiation for treatment planning. Materials and Methods: A systematic literature search was conducted through PubMed, Google Scholar, and Web of Science, over an initial five-year time span, from VI-RADS’ inception (May 2018) to November 2023. Studies reporting VI-RADS’ diagnostic performance with histopathological confirmation and interobserver agreement data were included. The diagnostic accuracy was assessed using sensitivity and specificity, while interobserver agreement was evaluated using Cohen’s κ coefficient. Results: Nine studies comprising 1249 participants met the inclusion criteria. Using a VI-RADS score cutoff of ≥3, the pooled sensitivity and specificity for detecting muscle invasion were 88.2% and 80.6%, respectively. Interobserver agreement showed excellent consistency with a mean κ value of 0.82. Individual study sensitivities ranged from 74.1% to 94.6%, while specificities varied from 43.9% to 96.5%. Conclusions: VI-RADS demonstrates high diagnostic accuracy and excellent interobserver agreement in BC staging, supporting its role as a reliable non-invasive diagnostic tool. However, it should be used as a complementary tool to, not a replacement for, histopathological confirmation. Moreover, the variability in specificity suggests the need for standardized training and interpretation protocols. Clinical correlation and adequate reader experience are essential for optimal implementation. Future integration with pathological data may further enhance its predictive value. Full article
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<p>Flow diagram of search algorithm.</p>
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<p>Multiparametric magnetic resonance imaging of the pelvis, at initial presentation of a bladder tumor case, scored as VI-RADS 4, on a 1.5-Tesla machine: (<b>A</b>) post-contrast fat-saturated axial T1-weighted sequence; (<b>B</b>) axial T2-weighted sequence; (<b>C</b>) diffusion-weighted imaging (DWI), axial sequence; (<b>D</b>) apparent diffusion coefficient (ADC) axial map. The mean ADC value for this tumor was 0.85 × 10<sup>−3</sup> mm<sup>2</sup>/s.</p>
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<p>Multiparametric magnetic resonance imaging of the pelvis, at initial presentation of a bladder tumor case, with an indwelling Foley catheter, scored as VI-RADS 5, on a 1.5-Tesla machine: (<b>A</b>) axial T2-weighted sequence; (<b>B</b>) sagittal T2-weighted sequence; (<b>C</b>) diffusion-weighted imaging (DWI), axial sequence; (<b>D</b>) apparent diffusion coefficient (ADC) axial map. The mean ADC value for this tumor was 0.82 × 10<sup>−3</sup> mm<sup>2</sup>/s.</p>
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12 pages, 245 KiB  
Review
Technical Modifications Employed in RARP to Improve Early Continence Recovery: A Literature Review
by Ernesto Di Mauro, Roberto La Rocca, Francesco Di Bello, Ugo Amicuzi, Pasquale Reccia, Luigi De Luca, Francesco Paolo Calace, Michelangelo Olivetta, Gennaro Mattiello, Pietro Saldutto, Pierluigi Russo, Lorenzo Romano, Lorenzo Spirito, Carmine Sciorio, Biagio Barone, Felice Crocetto, Francesco Mastrangelo, Giuseppe Celentano, Antonio Tufano, Luigi Napolitano and Vincenzo Maria Altieriadd Show full author list remove Hide full author list
Life 2025, 15(3), 415; https://doi.org/10.3390/life15030415 - 7 Mar 2025
Viewed by 77
Abstract
Prostate cancer presents a substantial challenge, necessitating a delicate balance between effective treatment and preserving the overall quality of life for men, while robot-assisted radical prostatectomy (RARP) stands as the premier surgical approach, with a negligible rate of patients who remained incontinent. This [...] Read more.
Prostate cancer presents a substantial challenge, necessitating a delicate balance between effective treatment and preserving the overall quality of life for men, while robot-assisted radical prostatectomy (RARP) stands as the premier surgical approach, with a negligible rate of patients who remained incontinent. This review explores various technical modifications employed in RARP to improve early continence recovery, offering a summary of their implementation and potential benefits. Techniques like bladder neck preservation, subapical urethral dissection, and nerve-sparing approaches are critically discussed, highlighting their role in minimizing continence issues and ensuring a better post-operative experience for patients with prostate cancer. Full article
(This article belongs to the Special Issue Prostate Cancer: 3rd Edition)
21 pages, 5495 KiB  
Article
Repurposing ProTAME for Bladder Cancer: A Combined Therapeutic Approach Targeting Cell Migration and MMP Regulation
by Ihsan Nalkiran and Hatice Sevim Nalkiran
Biology 2025, 14(3), 263; https://doi.org/10.3390/biology14030263 - 5 Mar 2025
Viewed by 189
Abstract
Bladder cancer, the fourth most common cancer type among men, remains a therapeutic challenge due to its heterogeneity and frequent development of chemoresistance. Cisplatin-based chemotherapy, often combined with gemcitabine, is the standard treatment, yet resistance and off-target effects in non-cancerous tissues limit its [...] Read more.
Bladder cancer, the fourth most common cancer type among men, remains a therapeutic challenge due to its heterogeneity and frequent development of chemoresistance. Cisplatin-based chemotherapy, often combined with gemcitabine, is the standard treatment, yet resistance and off-target effects in non-cancerous tissues limit its efficacy. This study evaluated the effects of cisplatin, gemcitabine, and the APC/C inhibitor proTAME, both individually and in combination, on cell migration and MMP2/MMP9 expression in RT4 bladder cancer and ARPE-19 normal epithelial cells. Molecular docking analyses were conducted to investigate the interactions of these compounds with MMP2 and MMP9. IC20 values for gemcitabine, cisplatin, and proTAME were applied in scratch-wound healing and quantitative real-time PCR (qRT-PCR) assays. Docking results predicted that proTAME may interact favorably with MMP2 (−9.2 kcal/mol) and MMP9 (−8.7 kcal/mol), showing high computational binding affinities and potential key hydrogen bonds; however, these interactions require further experimental validation. Scratch-wound healing and qRT-PCR assays demonstrated that proTAME-containing combinations were associated with reduced cell migration and decreased MMP2 and MMP9 expression in RT4 cells. Cisplatin combined with proTAME showed the most pronounced reduction in MMP expression and cell migration, with proTAME alone also exhibiting notable inhibitory effects. In ARPE-19 cells, gemcitabine and cisplatin upregulated MMP2 and MMP9 expression, suggesting a potential stress response, whereas proTAME mitigated this effect. These differential effects show the importance of tumor-specific responses in RT4 cells, where proTAME shows promise in enhancing the efficacy of chemotherapy by modulating MMP-related pathways involved in tumor migration and invasion. In conclusion, this study highlights the potential of proTAME as a repurposed agent in bladder cancer treatment due to its association with reduced cell migration and MMP downregulation. While these in vitro and in silico findings suggest a promising role for proTAME in combination therapies, further validation in advanced preclinical models is necessary to assess its therapeutic applicability and safety. Full article
(This article belongs to the Special Issue Cancer and Signalling: Targeting Cellular Pathways)
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<p>The structures of the therapeutic agents and ligands used in the molecular docking study are shown. (<b>a</b>) represents the 2D structure of proTAME. (<b>b</b>) illustrates gemcitabine, while (<b>c</b>) shows cisplatin. (<b>d</b>) presents the small-molecule ligand I52, and (<b>e</b>) depicts the 2D structure of the small-molecule ligand NFH. The chemical structures used in this figure were downloaded and modified from the PubChem database, <a href="https://pubchem.ncbi.nlm.nih.gov" target="_blank">https://pubchem.ncbi.nlm.nih.gov</a> (accessed on 9 October 2024).</p>
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<p>Molecular docking interactions of proTAME, gemcitabine, cisplatin, and I52 with MMP2. (<b>a</b>,<b>b</b>) ProTAME–MMP2: 3D visualization (<b>a</b>) demonstrates stable positioning of proTAME within the active site of MMP2, supported by interactions with key residues, as detailed in the 2D interaction map (<b>b</b>). (<b>c</b>,<b>d</b>) Gemcitabine–MMP2: 3D visualization (<b>c</b>) shows gemcitabine effectively bound to active site of MMP2, with the 2D interaction map (<b>d</b>) outlining residue-specific interactions. (<b>e</b>,<b>f</b>) Cisplatin–MMP2: 3D visualization (<b>e</b>) illustrates the positioning of cisplatin within the active site of MMP2, with the 2D interaction map (<b>f</b>) displaying key stabilizing interactions. (<b>g</b>,<b>h</b>) I52–MMP2: 3D visualization (<b>g</b>) highlights strong binding of I52 to the active site of MMP2, with the 2D interaction map (<b>h</b>) summarizing its stabilizing interactions. This figure highlights the varying binding affinities and interaction networks of these ligands within the active site of MMP2.</p>
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<p>Molecular docking interactions of proTAME, gemcitabine, cisplatin, and NFH with MMP9. (<b>a</b>,<b>b</b>) ProTAME–MMP9: 3D visualization (<b>a</b>) demonstrates the stable binding of proTAME within the active site of MMP9, supported by interactions with surrounding residues. The 2D interaction map (<b>b</b>) highlights key stabilizing interactions, including hydrogen bonds and other forces. (<b>c</b>,<b>d</b>) Gemcitabine–MMP9: 3D visualization (<b>c</b>) shows the effective positioning of gemcitabine within the active site of MMP9, with the 2D interaction map (<b>d</b>) displaying residue-specific interactions contributing to binding. (<b>e</b>,<b>f</b>) Cisplatin–MMP9: 3D visualization (<b>e</b>) illustrates binding of cisplatin to the active site of MMP9, stabilized by multiple interactions as shown in the 2D interaction map (<b>f</b>). (<b>g</b>,<b>h</b>) NFH–MMP9: 3D visualization (<b>g</b>) highlights the positioning of NFH and interactions within the active site of MMP9, with the 2D interaction map (<b>h</b>) summarizing key hydrogen bonds and stabilizing forces. This figure emphasizes the varying binding affinities and interaction networks of these ligands with MMP9.</p>
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<p>Inhibition of cell migration in ARPE-19 and RT4 cells by cisplatin, gemcitabine, and proTAME treatments in scratch-wound healing assay. (<b>a</b>,<b>d</b>) The images of scratch-wound healing assays performed on ARPE-19 (<b>a</b>) and RT4 (<b>d</b>) cells at 0, 24, and 48 h post-treatment. The cells were treated with DMSO control, cisplatin, gemcitabine, proTAME, or combinations of cisplatin+proTAME, gemcitabine+proTAME, gemcitabine+cisplatin, and gemcitabine+cisplatin+proTAME. Images represent one of three independent replicates (<span class="html-italic">n</span> = 3), with three technical replicates per condition. Images were captured using an inverted microscope at 4× magnification. (<b>b</b>,<b>e</b>) Quantification of the scratch-wound area (µm<sup>2</sup>) over time for ARPE-19 (<b>b</b>) and RT4 (<b>e</b>) cells, with measurements taken at 0, 24, and 48 h. The data show the reduction in scratch area across different treatment groups, indicating varying degrees of cell migration inhibition. (<b>c</b>,<b>f</b>) The percentage of the scratch-wound area remaining at 48 h relative to the initial wound size (0 h) for ARPE-19 (<b>c</b>) and RT4 (<b>f</b>) cells.</p>
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<p>Effects of cisplatin, gemcitabine, and proTAME on MMP2 and MMP9 gene expression in ARPE-19 and RT4 cells. (<b>a</b>) MMP2 gene expression fold change in ARPE-19 and RT4 cells following treatment with cisplatin, gemcitabine, proTAME, and their combinations. (<b>b</b>) MMP2 gene expression heat map visualization. (<b>c</b>) MMP9 gene expression fold change in ARPE-19 and RT4 cells under the same treatment conditions as (<b>a</b>). (<b>d</b>) MMP9 gene expression heat map visualization. Gene expression levels were normalized to GAPDH, and fold changes were calculated using the 2<sup>−ΔΔCt</sup> method. The data are presented as fold change relative to the ARPE-19 untreated control, with statistical comparisons conducted against the untreated control for cisplatin-, gemcitabine-, and cisplatin+gemcitabine-treated groups. Statistical significance is indicated as follows: ns: non-significant, *: <span class="html-italic">p</span> &lt; 0.05, **: <span class="html-italic">p</span> &lt; 0.01, ***: <span class="html-italic">p</span> &lt; 0.001. Statistical analyses were performed for proTAME, cisplatin+proTAME, gemcitabine+proTAME, and gemcitabine+cisplatin+proTAME groups compared to DMSO control. The statistical significance is indicated as follows: ns (bold): non-significant, §: <span class="html-italic">p</span> &lt; 0.05, §§: <span class="html-italic">p</span> &lt; 0.01, §§§: <span class="html-italic">p</span> &lt; 0.001. The statistical significance of RT4 untreated control was compared to ARPE-19 untreated control. All experiments were performed with three independent biological replicates, each consisting of three technical replicates, and data are presented as mean ± standard deviation (SD) from three independent experiments.</p>
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10 pages, 1269 KiB  
Article
The Impact of the Localization of Metastasis in Bladder Cancer Patients with Recurrence After Cystectomy
by Mads Aamand, Simone Buchardt Brandt, Rikke Vilsbøll Milling and Jørgen Bjerggaard Jensen
Cancers 2025, 17(5), 867; https://doi.org/10.3390/cancers17050867 - 3 Mar 2025
Viewed by 203
Abstract
Background/Objectives: The aim of this study is to assess the prognostic implications of metastatic anatomical location in patients with recurrent bladder cancer (BC) after cystectomy. Methods: The study is a retrospective cohort study. All data were collected from a clinical database from Aarhus [...] Read more.
Background/Objectives: The aim of this study is to assess the prognostic implications of metastatic anatomical location in patients with recurrent bladder cancer (BC) after cystectomy. Methods: The study is a retrospective cohort study. All data were collected from a clinical database from Aarhus University Hospital. Kaplan–Meier curves were used to analyse survival probabilities. Crude and adjusted Cox regression was used to calculate the hazard ratios (HRs) for overall mortality between different locations of metastases and the number of metastases. Results: In total, 180/664 (27.1%) patients who underwent radical cystectomy as a treatment of BC in the time period from 2015 to 2021 ultimately developed recurrent disease. The median follow-up period was 433 days (Q1: 256, Q3; 847). In a crude analysis for overall mortality, patients with both lymph node and distant organ metastasis had a worse prognosis than patients with lymph node metastasis only (HR = 2.25 (95% CI: 1.36–3.75, p = 0.002)). In the adjusted analysis, patients with ≥2 metastatic sites had higher hazard than patients with only a single site of recurrence (HR = 1.63 (95% CI: 1.15–2.33, p = 0.01)). Patients with organ metastasis had higher hazard ratios than patients with lymph node metastases and local recurrence only (HR = 1.74 (95% CI: 1.07–2.84, p = 0.026)). When analysing patients with single metastasis, there was a statistically significant difference in overall survival probability in the following groups: lymph node metastasis, other organ metastases, bone metastasis (p = 0.04). Conclusions: This study shows potentially clinically relevant associations between the anatomical location of metastases and patients’ prognosis. Furthermore, we were able to demonstrate an association between a higher number of metastatic sites and a worse prognosis. Full article
(This article belongs to the Section Cancer Metastasis)
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<p>Kaplan–Meier curves. Survival probability as a function of time measured in days. (<b>a</b>) Groups divided in single metastasis and ≥2 metastases. (<b>b</b>) Groups divided in Lnn: “Only lymph node metastases”, Lnn + Dis: “Lymph node and distant organ metastases”, Only Dis: “Only distant organ metastases”. (<b>c</b>–<b>e</b>) Groups divided in “Lnn + local”: “Lymph node and local recurrence”, “Other met”: “Other organ metastases” and lung, bone, and liver, respectively—both as single and combined with other organ metastases.</p>
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<p>Kaplan–Meier plots on single metastasis analysis. (<b>a</b>) Compares survival probability in the following groups: “Lymph node metastasis”, “Other organ metastases”, “Lung metastasis”. (<b>b</b>) Compares survival probability in the following groups: “Lymph node metastasis”, “Other organ metastases”, “Bone metastasis”.</p>
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11 pages, 490 KiB  
Article
Patient-Reported Urinary Symptom Progression After Bacillus Calmette–Guerin Therapy for Bladder Cancer
by Zorawar Singh, Ananth Punyala, Christina Sze, Naeem Bhojani, Kevin C. Zorn, Dean Elterman and Bilal Chughtai
Uro 2025, 5(1), 4; https://doi.org/10.3390/uro5010004 - 28 Feb 2025
Viewed by 205
Abstract
Background/Objectives: Lower urinary tract symptoms (LUTs) are commonly reported complications of intravesical Bacillus Calmette–Guerin (BCG) instillation for non-muscle invasive bladder cancer; however, there is limited characterization of the severity of the symptoms. We aim to explore the progression of LUTs with BCG treatment [...] Read more.
Background/Objectives: Lower urinary tract symptoms (LUTs) are commonly reported complications of intravesical Bacillus Calmette–Guerin (BCG) instillation for non-muscle invasive bladder cancer; however, there is limited characterization of the severity of the symptoms. We aim to explore the progression of LUTs with BCG treatment for bladder cancer. Methods: Patients were given the Overactive Bladder Questionnaire Short Form (OAB-q SF) to complete prior to their weekly BCG instillation during their primary six-week induction course. Mean symptom scores were compared for weeks 2 through 6 to baseline scores (week 1) utilizing two-sample tests. Subgroup analysis was conducted to identify cohorts at increased risk for urinary symptom progression. Simple linear regression was performed to determine the change in mean symptom scores over time. Results: A total of 60 patients completed the full six-week induction course and completed the required questionaries. Intravesical BCG administration was associated with no significant change in scores across either the symptom bothers or HFQL surveys, which were taken independently or in aggregate. No statistically significant differences in symptom scores were found between subgroups created based on demographic variables, tumor characteristics, or clinical presentation. Conclusions: Although intravesical BCG may cause acute urinary symptoms, it does not seem to impact a patient’s baseline urinary symptom profile. This is important when counseling patients about the perceived chronic urinary symptom risk associated with BCG treatment. Full article
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<p>Mean symptom score (BCG q Overall, BCG q Symptom Bother, and BCG HFQL) during induction BCG with associated table highlighting regression equations and 95% CI/<span class="html-italic">p</span>-values. * BCG: Bacillus Calmette–Guerin ** HFQL: health-related quality of life.</p>
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11 pages, 1093 KiB  
Article
Urothelial Bladder Carcinoma in Young and Elderly Patients: Pathological Insights and Age-Related Variations
by Andrada-Claudia Tătar, Andrada Loghin, Adela Nechifor-Boilă, Andrada Raicea, Maria-Cătălina Popelea, Călin Chibelean, Raul-Dumitru Gherasim and Angela Borda
Cancers 2025, 17(5), 845; https://doi.org/10.3390/cancers17050845 - 28 Feb 2025
Viewed by 215
Abstract
Background/Objectives: UBC demonstrates a relatively low prevalence in patients under 50 years old. Our study aimed to compare the pathological characteristics of UBC in young and elderly patients and to assess the age-related variations in these characteristics. Methods: This retrospective study from January [...] Read more.
Background/Objectives: UBC demonstrates a relatively low prevalence in patients under 50 years old. Our study aimed to compare the pathological characteristics of UBC in young and elderly patients and to assess the age-related variations in these characteristics. Methods: This retrospective study from January 2018 to December 2022 encompassed 762 patients with an initial diagnosis of UBC. To evaluate the pathological characteristics of UBC in young patients, compared to elderly patients, we divided our cohort using a cut-off age of 50 years. Additionally, to evaluate the age-dependent variations in these characteristics, we further stratified our patients into three age groups (≤50, 51–70, and >70 years old). Results: Of the 762 patients included in our study, 37 (4.86%) were young (≤50 years old), with a median age of 44 and a M:F ratio of 3.11:1. Conventional UC was the most common histology (86.5%). Regarding tumour grade, we noticed a higher prevalence of PUNLMP (10.8% versus 2.3%) and LGPUC (45.9% versus 37.1%) and a lower prevalence of HGPUC (43.2% versus 60%) and CIS (0% versus 0.6%) in young patients (p = 0.008). In this group, the pTa stage revealed a higher prevalence (64.9% versus 46.8%), while pT1 and pT2 showed a lower prevalence (32.1% versus 18.9% and 20.6% versus 16.2%) (p = 0.179). All results remained consistent when the cohort was stratified into three age groups, showing age-related variations (p = 0.001 and p = 0.089, respectively). Conclusions: In young patients, UBC tends to be of a lower grade and stage compared to elderly patients, and these characteristics demonstrate a gradual age-related stratification. Full article
(This article belongs to the Special Issue Histopathology of Urological Cancers)
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<p>PRISMA-like flow chart for patients’ inclusion and exclusion criteria. TURBT: transurethral resection of the bladder tumour.</p>
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<p>Pathological characteristics in young versus elderly patients. (<b>A</b>) Tumour grade. (<b>B</b>) Tumour stage.</p>
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<p>Pathological characteristics in the three age groups. (<b>A</b>) Tumour grade. (<b>B</b>) Tumour stage.</p>
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20 pages, 441 KiB  
Review
A Personalized, Risk-Based Approach to Active Surveillance for Prostate Cancer with Takeaways from Broader Oncology Practices: A Mixed Methods Review
by Jeroen J. Lodder, Sebastiaan Remmers, Roderick C. N. van den Bergh, Arnoud W. Postema, Pim J. van Leeuwen and Monique J. Roobol
J. Pers. Med. 2025, 15(3), 84; https://doi.org/10.3390/jpm15030084 - 25 Feb 2025
Viewed by 316
Abstract
Background/Objectives: To summarize the current state of knowledge regarding personalized, risk-based approaches in active surveillance (AS) for prostate cancer (PCa) and to explore the lessons learned from AS practices in other types of cancer. Methods: This mixed methods review combined a [...] Read more.
Background/Objectives: To summarize the current state of knowledge regarding personalized, risk-based approaches in active surveillance (AS) for prostate cancer (PCa) and to explore the lessons learned from AS practices in other types of cancer. Methods: This mixed methods review combined a systematic review and a narrative review. The systematic review was conducted according to the Preferred Reporting Items for Systematic rviews and Meta-Analyses (PRISMA) guidelines, with searches performed in the Medline, Embase, Web of Science, Cochrane Central Register of Controlled Trials, and Google Scholar databases. Only studies evaluating personalized, risk-based AS programs for PCa were included. The narrative review focused on AS approaches in other solid tumors (thyroid, breast, kidney, and bladder cancer) to contextualize the findings and highlight lessons learned. Results: After screening 3137 articles, 9 were suitable for inclusion, describing the following four unique risk-based AS tools: PRIAS, Johns Hopkins, Canary PASS, and STRATCANS. These models were developed using data from men with low-risk (Grade Group 1) disease, with little to no magnetic resonance imaging (MRI) data. They used patient information such as (repeated) prostate-specific antigen (PSA) measurements and biopsy results to predict the risk of upgrading at the next biopsy or at radical prostatectomy, or to assign a patient to a pre-defined risk category with a corresponding pre-defined follow-up (FU) regimen. Performance was moderate across models, with the area under the curve/concordance index values ranging from 0.58 to 0.85 and calibration was generally good. The PRIAS, Canary PASS, and STRATCANS models demonstrated the benefits of less burdensome biopsies, clinic visits, and MRIs during FU when used, compared to current one-size-fits-all practices. Although little is known about risk-based AS in thyroid, breast, kidney, and bladder cancer, learning from their current practices could further refine patient selection, streamline monitoring protocols, and address adoption barriers, improving AS’s overall effectiveness in PCa management. Conclusions: Personalized, risk-based AS models allow for a reduction in the FU burden for men at low risk of progression while maintaining sensitive FU visits for those at higher risk. The comparatively limited evidence and practice of risk-based AS in other cancer types highlight the advanced state of AS in PCa. Full article
(This article belongs to the Section Methodology, Drug and Device Discovery)
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<p>PRISMA flowchart of the review search.</p>
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15 pages, 2510 KiB  
Article
Silver Dimolybdate Nanorods: In Vitro Anticancer Activity Against Breast and Prostate Tumors and In Vivo Pharmacological Insights
by João Victor Barbosa Moura, Natália Cristina Gomes-da-Silva, Luciana Magalhães Rebêlo Alencar, Wellington Castro Ferreira, Cleânio da Luz Lima and Ralph Santos-Oliveira
Pharmaceutics 2025, 17(3), 298; https://doi.org/10.3390/pharmaceutics17030298 - 24 Feb 2025
Viewed by 262
Abstract
Background: The development of nanostructured materials for cancer therapy has garnered significant interest due to their unique physicochemical properties, including enhanced surface area and tunable electronic structures, which can facilitate targeted drug delivery and oxidative stress modulation. This study investigates the anticancer [...] Read more.
Background: The development of nanostructured materials for cancer therapy has garnered significant interest due to their unique physicochemical properties, including enhanced surface area and tunable electronic structures, which can facilitate targeted drug delivery and oxidative stress modulation. This study investigates the anticancer potential of monoclinic silver dimolybdate nanorods (m-Ag₂Mo₂O₇) against aggressive breast (MDA-MB-231) and prostate (PC-3) cancer cells and explores their in vivo pharmacokinetic behavior. Methods: m-Ag₂Mo₂O₇ nanorods were synthesized via a hydrothermal method and characterized using XRD, SEM, Raman, and FTIR spectroscopy. In vitro cytotoxicity was evaluated using MTT assays on MDA-MB-231 and PC-3 cell lines across concentrations ranging from 1.56 to 100 µg/mL. In vivo biodistribution and radiopharmacokinetics were assessed using technetium-99m-labeled nanorods in male Swiss rats, with gamma counting employed for tissue uptake analysis and pharmacokinetic parameter determination. Results: m-Ag₂Mo₂O₇ nanorods exhibited a modest cytotoxic effect on MDA-MB-231 cells, with 50 µg/mL reducing cell viability by 23.5% (p < 0.05), while no significant cytotoxicity was observed in PC-3 cells. In vivo studies revealed predominant accumulation in the stomach, liver, spleen, and bladder, indicating reticuloendothelial system uptake and renal clearance. Pharmacokinetic analysis showed a rapid systemic clearance (half-life ~6.76 h) and a low volume of distribution (0.0786 L), suggesting primary retention in circulation with minimal off-target diffusion. Conclusions: While m-Ag₂Mo₂O₇ nanorods display limited standalone cytotoxicity, their ability to induce oxidative stress and favorable pharmacokinetic profile support their potential as adjuvant agents in cancer therapy, particularly for chemoresistant breast cancers. Further studies are warranted to elucidate their molecular mechanisms, optimize combinatorial treatment strategies, and assess long-term safety in preclinical models. Full article
(This article belongs to the Special Issue Recent Advances in Nanotechnology Therapeutics)
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<p>(<b>a</b>) X-ray diffraction pattern of m-Ag<sub>2</sub>Mo<sub>2</sub>O<sub>7</sub> nanorods obtained by hydrothermal synthesis. (<b>b</b>) Representation of the crystal structure of the m-Ag<sub>2</sub>Mo<sub>2</sub>O<sub>7</sub> crystal (Mo—Green, Ag—Silver, and O—Red atoms), showing the [MoO<sub>6</sub>] clusters connected by oxygen atoms forming distorted/deformed octahedrons. (<b>c</b>) Low- and (<b>d</b>) high-magnification SEM images of m-Ag<sub>2</sub>Mo<sub>2</sub>O<sub>7</sub> nanorods.</p>
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<p>(<b>a</b>) Raman and (<b>b</b>) FTIR spectra of m-Ag<sub>2</sub>Mo<sub>2</sub>O<sub>7</sub> nanorods. Inset: Magnification of the spectral region of 550–100 cm<sup>−1</sup> where the Raman modes have low intensity.</p>
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<p>(<b>A</b>) MDA-MB-231 and PC-3: cell viability after treatment with different concentrations of m-Ag<sub>2</sub>Mo<sub>2</sub>O<sub>7</sub> nanorods using a human breast cancer cell line and a prostate tissue derived from a human, respectively. The results are expressed as the percentage of total cell viability (spectrophotometric readings at 450 nm) in the culture medium after the addition of a 1 mg/mL MTT solution (positive response). The height of the histogram bar is the mean ± SEM of three independent experiments. MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide. (<b>B</b>) The representative images of the key concentrations of m-Ag<sub>2</sub>Mo<sub>2</sub>O<sub>7</sub> (control; 100 μg/mL; 50 μg/mL; and 1.5 μg/mL) obtained from an inverted light microscope with a 10× objective lens. Scale bar: 20 μm. * means statically different.</p>
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<p>Biodistribution assay showing the tissue accumulation of m-Ag<sub>2</sub>Mo<sub>2</sub>O<sub>7</sub>.</p>
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<p>The main pharmacokinetic data derived from temporal reconstruction based on serial blood sampling. ** mean statically different.</p>
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11 pages, 1303 KiB  
Review
Serum Tumor Markers for Muscle-Invasive Bladder Cancer in Clinical Practice: A Narrative Review
by Chirag Doshi, Mazyar Zahir, Anosh Dadabhoy, Domenique Escobar, Leilei Xia and Siamak Daneshmand
Cancers 2025, 17(5), 728; https://doi.org/10.3390/cancers17050728 - 21 Feb 2025
Viewed by 313
Abstract
In recent decades, serum tumor markers (STMs) have emerged as valuable adjuncts in early cancer detection and post-treatment surveillance. STMs are inexpensive, minimally invasive, and readily accessible tools that can be used to diagnose cancers, monitor patients’ responses to treatment, and even detect [...] Read more.
In recent decades, serum tumor markers (STMs) have emerged as valuable adjuncts in early cancer detection and post-treatment surveillance. STMs are inexpensive, minimally invasive, and readily accessible tools that can be used to diagnose cancers, monitor patients’ responses to treatment, and even detect recurrence without imposing additional burdens on patients. Emerging evidence has demonstrated the reliability of STMs in the prognostication of bladder cancer (BC). However, their potential role extends beyond prognostication. This review intends to provide a multidimensional picture of STM applications in muscle-invasive bladder cancer (MIBC). In addition, we supplement this review with real-life clinical experiences from our institution to further illustrate the clinical feasibility of STMs in MIBC. Full article
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<p>Patient 1’s treatment course with Serum Tumor Markers. Note: STM values have been adjusted to fit within a graphical space. STM values were adjusted by dividing by their values by their respective upper limit of normal (CA 19-9: 37 U/mL; CA-125: 35 U/mL; CEA: 3 U/mL). As a result, any value greater than 1 is representative of an abnormal lab finding.</p>
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<p>Patient 2’s treatment course with Serum Tumor Markers. Note: STM values have been adjusted to fit within a graphical space. STM values were adjusted by dividing by their values by their respective upper limit of normal (CA 19-9: 37 U/mL; CA-125: 35 U/mL; CEA: 3 U/mL). As a result, any value greater than 1 is representative of an abnormal lab finding.</p>
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<p>Patient 3’s treatment course with Serum Tumor Markers. Note: STM values have been adjusted to fit within a graphical space. STM values were adjusted by dividing by their values by their respective upper limit of normal (CA 19-9: 37 U/mL; CA-125: 35 U/mL; CEA: 3 U/mL). As a result, any value greater than 1 is representative of an abnormal lab finding.</p>
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10 pages, 219 KiB  
Study Protocol
Evaluation of Reminder App for Optimization of Bladder Filling Status During Hypo-Fractionated Irradiation for Prostate Cancer: Protocol of REFILL-PAC-HYPO Trial
by Dirk Rades, Jan-Dirk Küter, Michael von Staden, Ahmed Al-Salool, Christian Ziemann, Stefan Janssen, Julia Koeck, Justus Domschikowski, Charlotte Kristiansen, Christine Vestergård Madsen, Marciana N. Duma, Tobias Bartscht, Jon Cacicedo and Florian Cremers
Clin. Pract. 2025, 15(3), 40; https://doi.org/10.3390/clinpract15030040 - 20 Feb 2025
Viewed by 206
Abstract
Background/Objectives: During radiotherapy for prostate cancer, the risk of radiation cystitis is increased if the volume of the bladder is small. According to previous studies, it is important that bladder volumes are ≥200 mL. Drinking protocols may be helpful in this context. Adherence [...] Read more.
Background/Objectives: During radiotherapy for prostate cancer, the risk of radiation cystitis is increased if the volume of the bladder is small. According to previous studies, it is important that bladder volumes are ≥200 mL. Drinking protocols may be helpful in this context. Adherence to such protocols can be challenging, and may be improved by an app reminding patients before each session of radiotherapy to drink a certain amount of water. Our prospective phase 2 trial (REFILL-PAC-HYPO, NCT06784115) evaluates the impact of a reminder app on bladder filling in prostate cancer patients treated with hypo-fractionated radiotherapy. Methods: Twenty-seven patients need to be recruited for the REFILL-PAC-HYPO trial. Radiotherapy, preferably with volumetric-modulated arc therapy, uses hypo-fractionation with 20 × 3.0 Gy over four weeks. An app reminds patients to drink water (300 mL) 45 min before each session of hypo-fractionated irradiation. On the last day of their treatment, patients are asked about their satisfaction with the app. In the case of a dissatisfaction rate of >20%, the app requires modifications. If this rate is >40%, the app is considered not useful. Additionally, patients are asked about the impact of their participation in the trial and using the app on their general attitude towards health technology. Furthermore, the phase 2 cohort is compared to a historical control group treated with hypo-fractionated radiotherapy during recent years but not supported by an app. The REFILL-PAC-HYPO trial will contribute to identifying the potential value of a reminder app for bladder filling during hypo-fractionated radiotherapy for prostate cancer. Full article
15 pages, 1252 KiB  
Article
Perioperative Intensive Smoking Cessation Intervention Among Smokers Who Underwent Transurethral Resection of Bladder Tumor (TURBT) in Two Different Settings: A Randomized Controlled Trial
by Line N. Lydom, Susanne V. Lauridsen, Mie S. Liljendahl, Anne V. Schmedes, Ulla N. Joensen and Hanne Tønnesen
Cancers 2025, 17(4), 713; https://doi.org/10.3390/cancers17040713 - 19 Feb 2025
Viewed by 357
Abstract
Background/Objective: Smoking is an individual risk factor for bladder cancer. Many patients are still smoking at the time of their diagnosis, yet few trials have examined smoking cessation interventions (SCIs) in relation to transurethral resection of the bladder tumor (TURBT). This study therefore [...] Read more.
Background/Objective: Smoking is an individual risk factor for bladder cancer. Many patients are still smoking at the time of their diagnosis, yet few trials have examined smoking cessation interventions (SCIs) in relation to transurethral resection of the bladder tumor (TURBT). This study therefore aimed to compare the efficacy of a hospital-based 6-week intensive SCI with standard treatment among this patient group. Methods: A parallel-arm randomized controlled trial was conducted from December 2021 to March 2024 at two university hospital urology departments in Denmark. A total of 38 daily smokers undergoing TURBT were allocated to the hospital-based intensive SCI, including weekly meetings, patient education, motivational support, and complimentary nicotine replacement therapy or the standard treatment with very brief advice and referral to the same intensive SCI at a municipality clinic. The primary outcome was smoking cessation at the end of the intervention, assessed through participant interviews. The secondary outcomes included continuous abstinence at three and six months, quality of life, and frailty. Analyses were performed as intention-to-treat. Results: After six weeks, 37% in the hospital-based group and 6% in the standard group achieved smoking cessation (p = 0.042). At three and six months the quit rates were, 37% and 26% in the hospital-based group, compared to 0% and 0% in the standard group, respectively. No significant differences in quality of life or frailty were found. Conclusions: This trial found that hospital-based intensive SCI increased cessation rates compared to standard treatment. It would be valuable to evaluate the impact on postoperative complications, cancer prognosis, and long-term cessation in a sizeable new study. Full article
(This article belongs to the Section Clinical Research of Cancer)
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<p>Patient trial profile. SCI = smoking cessation intervention.</p>
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<p>Trends in cigarette use at baseline and follow-up time points. Each dashed blue line represents an individual participant’s cigarette consumption, while the solid red line represents the median cigarette use at each time point. (<b>a</b>): Hospital-based group; (<b>b</b>): Standard treatment group. Baseline cigarette use was categorized as: 1–10/day = 5, 11–20/day = 15, and 21–30/day = 25. Missing follow-up values were imputed using the participant’s baseline value.</p>
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16 pages, 1995 KiB  
Article
Liquid Biopsy Based Bladder Cancer Diagnostic by Machine Learning
by Ērika Bitiņa-Barlote, Dmitrijs Bļizņuks, Sanda Siliņa, Mihails Šatcs, Egils Vjaters, Vilnis Lietuvietis, Miki Nakazawa-Miklaševiča, Juris Plonis, Edvīns Miklaševičs, Zanda Daneberga and Jānis Gardovskis
Diagnostics 2025, 15(4), 492; https://doi.org/10.3390/diagnostics15040492 - 18 Feb 2025
Viewed by 373
Abstract
Background/Objectives: The timely diagnostics of bladder cancer is still a challenge in clinical settings. The reliability of conventional testing methods does not reach desirable accuracy and sensitivity, and it has an invasive nature. The present study examines the application of machine learning [...] Read more.
Background/Objectives: The timely diagnostics of bladder cancer is still a challenge in clinical settings. The reliability of conventional testing methods does not reach desirable accuracy and sensitivity, and it has an invasive nature. The present study examines the application of machine learning to improve bladder cancer diagnostics by integrating miRNA expression levels, demographic routine laboratory test results, and clinical data. We proposed that merging these datasets would enhance diagnostic accuracy. Methods: This study combined molecular biology methods for liquid biopsy, routine clinical data, and application of machine learning approach for the acquired data analysis. We evaluated urinary exosome miRNA expression data in combination with patient test results, as well as clinical and demographic data using three machine learning models: Random Forest, SVM, and XGBoost classifiers. Results: Based solely on miRNA data, the SVM model achieved an ROC curve area of 0.75. Patient analysis’ clinical and demographic data obtained ROC curve area of 0.80. Combining both data types enhanced performance, resulting in an F1 score of 0.79 and an ROC of 0.85. The feature importance analysis identified key predictors, including erythrocytes in urine, age, and several miRNAs. Conclusions: Our findings indicate the potential of a multi-modal approach to improve the accuracy of bladder cancer diagnosis in a non-invasive manner. Full article
(This article belongs to the Section Machine Learning and Artificial Intelligence in Diagnostics)
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<p>Flowchart of data analysis. FR—fold regulation; SMV—support vector machine; XGBoost—extreme gradient boosting.</p>
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<p>Areas under curve (AUC) after analysing miRNA levels by Random Forest (<b>A</b>), SMV (<b>B</b>), and XGBoost model (<b>C</b>). Confusion matrix for the Random Forest (<b>D</b>), SMV (<b>E</b>), and XGBoost (<b>F</b>) model trained with differentially expressed miRNAs.</p>
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<p>Areas under curve (AUC) after analysing the clinical data set by Random Forest (<b>A</b>), SMV (<b>B</b>) and XGBoost model (<b>C</b>). Confusion matrix for the Random Forest (<b>D</b>), SMV (<b>E</b>), and XGBoost (<b>F</b>) model trained with a clinical data set.</p>
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<p>Areas under curve (AUC) after analysing miRNA levels and the clinical data set combined by Random Forest (<b>A</b>), SMV (<b>B</b>), and XGBoost model (<b>C</b>). Confusion matrix for the Random Forest (<b>D</b>), SMV (<b>E</b>), and XGBoost (<b>F</b>) model trained with miRNA levels and the clinical data set combined.</p>
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<p>Feature importance analysis in a combined data set by three machine learning models: Random Forest (<b>A</b>), SVM (<b>B</b>), and XGBoost (<b>C</b>). Uri_test_er—eritocituria in dipstick urine analysis; Ur_test_leu—leucocituria in dipstick urine analysis; Ur-test_nitr—positive nitrite test in dipstick urine analysis; Arom_am—exposure to aromatic amines, Onc-farm_hist—oncological history in family; Chronic UCI—chronic urinary tract infection.</p>
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4 pages, 904 KiB  
Correction
Correction: Singh et al. Stat3 Inhibitors TTI-101 and SH5-07 Suppress Bladder Cancer Cell Survival in 3D Tumor Models. Cells 2024, 13, 1463
by Surya P. Singh, Gopal Pathuri, Adam S. Asch, Chinthalapally V. Rao and Venkateshwar Madka
Cells 2025, 14(4), 299; https://doi.org/10.3390/cells14040299 - 18 Feb 2025
Viewed by 192
Abstract
In the original publication [...] Full article
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<p>Effect of STAT3 inhibitors on proliferation of BCa spheroids. Representative images of spheroids generated using J82 (<b>A</b>), NBT-II (<b>B</b>), and MB49 (<b>C</b>) BCa cell lines. All images were captured at a 10X magnification. Growth curves of spheroid sizes (<b>D</b>). Schematic diagram illustrating treatment of spheroids with STAT3 inhibitors (<b>E</b>). Intracellular ATP content in (<b>I</b>–<b>K</b>) spheroids measured by luminescence on day six (<b>F</b>–<b>H</b>). Treatment with STAT3 inhibitors decreased the BCa spheroids size; bar represents 200 µM diameter (<b>I</b>–<b>K</b>). Spheroids were stained with calcein AM for live cells (green) and EtBr for dead cells (red). Representative images of control vs. treated BCa spheroids (<b>L</b>,<b>M</b>). All experiments were performed in triplicate (<span class="html-italic">n</span> = 3). Values are expressed as the mean ± SEM. Significance is indicated by * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.001, and *** <span class="html-italic">p</span> &lt; 0.0001.</p>
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<p>Effect of STAT3 inhibitors on proliferation of BCa spheroids. Representative images of spheroids generated using J82 (<b>A</b>), NBT-II (<b>B</b>), and MB49 (<b>C</b>) BCa cell lines. All images were captured at a 10X magnification. Growth curves of spheroid sizes (<b>D</b>). Schematic diagram illustrating treatment of spheroids with STAT3 inhibitors (<b>E</b>). Intracellular ATP content in (<b>I</b>–<b>K</b>) spheroids measured by luminescence on day six (<b>F</b>–<b>H</b>). Treatment with STAT3 inhibitors decreased the BCa spheroids size; bar represents 200 µM diameter (<b>I</b>–<b>K</b>). Spheroids were stained with calcein AM for live cells (green) and EtBr for dead cells (red). Representative images of control vs. treated BCa spheroids (<b>L</b>,<b>M</b>). All experiments were performed in triplicate (<span class="html-italic">n</span> = 3). Values are expressed as the mean ± SEM. Significance is indicated by * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.001, and *** <span class="html-italic">p</span> &lt; 0.0001.</p>
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23 pages, 347 KiB  
Conference Report
B2B: Bladder Cancer Summary
by Peter C. Black, Seth P. Lerner, Mihir M. Desai, Badrinath R. Konety, Shilpa Gupta, Amit Joshi, Karima Oualla, Senthil Rajappa, Vineet Talwar, Gagan Prakash and Simon Tanguay
Soc. Int. Urol. J. 2025, 6(1), 18; https://doi.org/10.3390/siuj6010018 - 17 Feb 2025
Viewed by 200
Abstract
The 6th Bench-to-Bedside Uro-Oncology: GU Cancers Triad Meeting, organized in conjunction with the 44th Annual Congress of the Société Internationale d’Urologie, was held on 25 October 2024, in New Delhi, India, and transmitted live on the SIU@U Congress platform [...] Full article
13 pages, 915 KiB  
Article
Risk Factors Predictive of Contralateral Recurrence of Upper Tract Urothelial Carcinoma Include Chronic Kidney Diseases and Postoperative Initiation of Dialysis
by Yi-Ru Wu, Ching-Chia Li, Yung-Shun Juan, Wei-Ming Li, Wen-Jeng Wu and Tsu-Ming Chien
Cancers 2025, 17(4), 664; https://doi.org/10.3390/cancers17040664 - 16 Feb 2025
Viewed by 300
Abstract
Background: The objective of the present study was to evaluate the impact of dialysis on patients with upper tract urothelial carcinoma (UTUC) who are undergoing surgical intervention, as well as to identify predictive factors linked to contralateral recurrence. Methods: A retrospective review was [...] Read more.
Background: The objective of the present study was to evaluate the impact of dialysis on patients with upper tract urothelial carcinoma (UTUC) who are undergoing surgical intervention, as well as to identify predictive factors linked to contralateral recurrence. Methods: A retrospective review was conducted on patients who underwent radical nephroureterectomy (RNU) for non-metastatic UTUC at our institution from 2000 to 2013. The contralateral recurrence rate was calculated using the Kaplan–Meier method, and multivariate logistic regression analysis was employed to examine the relationship between clinicopathological characteristics and contralateral recurrence. Results: A total of 593 patients were included in this analysis, of which 31 (5.8%) experienced metachronous recurrence on the contralateral side. Kaplan–Meier analysis indicated a statistically significant reduction in the contralateral recurrence-free survival rate among female patients (p = 0.040), those with a prior history of bladder cancer (p < 0.001), individuals presenting with multiple tumors (p = 0.011), patients with advanced chronic kidney disease (CKD) (p < 0.001), and those requiring postoperative dialysis (p < 0.001). In contrast, preoperative hemodialysis status did not show a significant correlation with contralateral recurrence (p = 0.08). The multivariate analysis identified a history of bladder cancer (hazard ratio (HR), 3.19; 95% confidence interval (CI), 1.2–8.4; p = 0.018), the necessity for new hemodialysis postoperatively (HR, 5.34; 95% CI, 1.3-25.6; p = 0.034), and advanced CKD (HR, 2.52; 95% CI, 1.4–4.9; p = 0.021) as independent risk factors associated with an increased rate of contralateral recurrence. Conclusions: In conclusion, advanced CKD, a history of bladder cancer, and the initiation of new dialysis following surgery were identified as independent prognostic indicators for contralateral recurrence in patients with initial unilateral UTUC undergoing RNU. It is recommended that patients exhibiting these three adverse characteristics undergo rigorous monitoring of the contralateral upper urinary tract throughout the follow-up period. Full article
(This article belongs to the Special Issue Cancer and Chronic Illness)
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<p>Kaplan-Meier estimates of survival in patients with UTUC based on contralateral recurrence. (<b>A</b>), OS. (<b>B</b>), CSS. (<b>C</b>), BRFS.</p>
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<p>Kaplan–Meier estimates of contralateral survival in patients with UTUC based on (<b>A</b>), gender. (<b>B</b>), bladder cancer history. (<b>C</b>), tumor number. (<b>D</b>), CKD status. (<b>E</b>), postoperative hemodialysis. (<b>F</b>), preoperative hemodialysis.</p>
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