Search Results (160)

Partial cystectomy is a surgical bladder-sparing option for selected patients with muscle-invasive bladder cancer (MIBC), urachal adenocarcinoma and diverticular bladder tumors. Partial cystectomy hold several advantages. It allows for definite pathology and accurate staging while avoiding side effects from radiation therapy and preserves the option for salvage radical therapy (radical cystectomy or radical radiotherapy). Patients should have a CT urogram, prostatic urethral biopsy and mapping biopsies or blue light cystoscopy to rule out multifocal disease or CIS. Small solitary MIBC patients without carcinoma in situ in an area of the bladder where resection can be performed with negative margin would be the ideal candidates for partial cystectomy. Neoadjuvant systemic therapy is recommended for patients undergoing partial cystectomy. Partial cystectomy can be performed either by open or robotic approaches. When compared to radical cystectomy, partial cystectomy affords a lower complication rate and length of stay and better quality of life. Recurrence-free survival, cancer-specific survival and overall survival at 5 years is 39–67%, 62–84% and 45–70%, respectively. Following partial cystectomy, patients should have three monthly cystoscopy and urinary cytology for the first 24 months followed by 6-monthly cystoscopy for year 3 and 4 and then yearly for life. Cross-sectional imaging should be performed every 3–6 months for the first 2–3 years and then annually for 5 years. Full article

Background and Objectives: Urothelial bladder carcinoma includes a spectrum of malignant lesions with heterogeneous molecular, biological, and clinical features and a variable risk of progression from non-muscle-invasive bladder cancer (NMIBC) to muscle-invasive disease (MIBC) and ultimately to metastatic urothelial carcinoma (mUC). Sarcopenia, a condition secondary to a catabolic state, is characterized by progressive loss of skeletal muscle mass and function and is highly prevalent across all stages of bladder cancer. This review aims to synthesize current evidence regarding the clinical impact of sarcopenia and its dynamic changes throughout the disease course. Materials and Methods: A narrative literature review was conducted using PubMed, Scopus, and Cochrane databases, incorporating the most relevant published sources. Search terms included “bladder carcinoma”, “sarcopenia”, “body composition”, “NMIBC”, and “MIBC”. Case reports and congress abstracts were excluded. Results: In NMIBC treated with intravesical Bacillus Calmette–Guérin (BCG), sarcopenia has been shown to have a negative predictive value in some studies. Among patients receiving neoadjuvant chemotherapy (NAC) for MIBC, sarcopenia has been associated with increased toxicity, dose reductions, and treatment delays. In the context of radical surgery, sarcopenia correlates with increased postoperative mortality and a higher rate of severe complications. In mUC, low muscle mass is a negative prognostic factor regardless of treatment type and is associated with chemotherapy-related hematologic toxicity, although it does not appear to predict immune-related adverse events (irAEs). Conclusions: Sarcopenia is a highly prevalent and clinically relevant phenotype of urothelial bladder cancer patients, impacting prognosis, treatment response, and chemotherapy toxicity. Incorporating sarcopenia with other relevant components of body composition (BC) and systemic inflammatory markers may facilitate the development of more robust risk scores. Current evidence is primarily limited by the retrospective design of most studies. Future prospective research is needed to clarify the prognostic role of sarcopenia and support its integration into routine clinical decision-making. Full article

Muscle-invasive bladder cancer (MIBC) is a biologically aggressive disease with high recurrence rates, despite advances in surgical and systemic therapies. Circulating tumor DNA (ctDNA), a tumor-specific fraction of cell-free DNA, has emerged as a promising non-invasive biomarker for the real-time assessment of tumor burden, treatment response, and minimal residual disease (MRD). This review explores the biological basis, detection technologies, and clinical utility of ctDNA in MIBC, highlighting its role in preoperative risk stratification, postoperative surveillance, and personalized decision-making for adjuvant and systemic therapies. We critically examine current evidence from pivotal trials and ongoing studies that support ctDNA’s prognostic and predictive value. Additionally, we discuss emerging applications, including ctDNA-guided immunotherapy, integration with imaging and molecular data, and potential to inform bladder-sparing strategies. While ctDNA presents technical and logistical challenges, its incorporation into prospective clinical workflows promises to enhance precision oncology and improve outcomes in patients with MIBC. Full article

Introduction: Radical cystectomy (RC) is the gold standard for urothelial cT2-4a, N0, M0 muscle-invasive bladder cancer (MIBC). However, bladder-sparing strategies (BSS) such as Trimodality Therapy (TMT) have emerged as alternative treatments for a select group of localized muscle-confined (cT2) urothelial bladder cancers. Accordingly, reliable preoperative staging and a reliable risk factor assessment linked to pathological upstaging play a key role in adequate counselling and patient selection for BSS. Patients and Methods: cT2 MIBC patients undergoing RC at our institution from 2014 to 2024 were reviewed. Preoperative staging modalities, demographics, and tumour and patient characteristics were assessed. Multivariable logistic regression was applied to explore the relative effect of confounders on any pathological upstaging from robot-assisted or open RC specimens. Subgroup analysis according to the local upstaging (>pT2) or nodal dissemination (pN+) was also performed. Results: N = 275 RCs were included (73.5% males, 26.5% females). Upstaging was documented in n = 141 (51%) cases. Of these, n = 125 (45.5%) were upstaged locally (>pT2) and n = 35 (23%) yielded pN+ disease. Preoperative parameters like gender, the number of TURBTs, previous BCG exposure, and concomitant CIS did not significantly influence the risk of any kind of upstaging (p > 0.05). At multivariable analysis, neoadjuvant chemotherapy (NAC) and multi-disciplinary team (MDT) discussion were found protective (odds ratio [OR]: 0.4, 95%CI 0.2–0.7, p = 0.001 and OR: 0.51, 95%CI 0.2–0.9, p = 0.01). Preoperative FDG-PET assessment yielded higher risk for later pN upstaging (OR: 1.8, 95%CI 1–3, p = 0.05). HG/G3 features at TURBT along with mixed/pure histology variants in RC specimens were the most relevant independent predictors for both any and pT upstaging (OR: 4.3, 95%CI 1–34, p = 0.04 and OR: 2.3, 95%CI 1.1–4.6, p = 0.02 for any upstaging and OR: 5.6, 95%CI 1.3–36, p = 0.02 and OR: 2.5, 95%CI 1.3–5, p = 0.01 for pT upstaging, respectively). Conclusions: In this study, over half of the patients undergoing RC for cT2 were upstaged at the final pathology. Therefore, adequate counselling and examining the non-conventional criteria for prognosis is mandatory in the contemporary era of bladder-preservation strategies. Full article

Background: Desmocollin3, a transmembrane protein, is expressed in the basal/suprabasal layer of normal stratified epithelium. DSC3 gene expression is described in muscle-invasive bladder cancer (MIBC). DSC3-protein-expressing recurrent non-muscle-invasive bladder cancer (NMIBC) had a durable response to CADI-03, a DSC3-specific active immunotherapy. Methods: We evaluated DSC3 protein expression and its correlation with tumor-infiltrating immune cells in bladder cancer. DSC3 gene expression and its correlation with 208 immune encoding genes, treatment outcome, and survival were evaluated using the “ARRAYEXPRESS” and “TCGA” datasets. Immune genes were grouped as tumor-controlling immune genes (TCIGs) and tumor-promoting immune genes (TPIGs) as per their functions. Results & conclusions: NMIBC had higher DSC3 expression compared to MIBC. More immune genes were correlated with DSC3 in MIBC (21) compared to NMIBC (11). Amongst the TCIGs, six in NMIBC and one in MIBC had a negative correlation while two in NMIBC and nine in MIBC had a positive correlation with DSC3. Amongst the TPIGs, nine in NMIBC and five in MIBC had a negative correlation. Seven TPIGs had a positive correlation with DSC3 in MIBC and none in NMIBC. Of the T cell exhaustion markers, none were correlated with DSC3 in MIBC. Among NMIBC, CTLA4 and TIGIT were the only markers of exhaustion that demonstrated a negative correlation with DSC3. DSC3 expression was also higher in p53 mutant compared to wild p53, non-papillary MIBC compared to papillary MIBC, and in basal, squamous molecular subtype compared to luminal MIBC. MIBC with lower DSC3 expression had better outcomes (response, survival) compared to those with higher DSC3 expression. Full article

Bladder cancer, especially muscle-invasive bladder cancer (MIBC), poses significant treatment challenges due to its aggressive nature and poor prognosis, often necessitating cisplatin-based chemotherapy. While cisplatin effectively reduces tumor burden, its nephrotoxic effects, specifically cisplatin-induced acute kidney injury (AKI), limit its clinical use. This study investigates SH3YL1 as a potential biomarker for bladder cancer progression and AKI. Plasma and urine SH3YL1 levels were measured in bladder cancer patients undergoing cisplatin treatment, showing elevated baseline levels compared to controls, suggesting a link with bladder cancer pathology rather than cisplatin-induced AKI. Functional network and Gene Ontology (GO) enrichment analyses identified SH3YL1’s interactions with NADPH oxidase pathways, particularly NOX family genes, and highlighted its roles in cell adhesion, migration, and cytoskeletal organization—processes critical for tumor invasiveness. Notably, SH3YL1 and NOX4 expression were significantly higher in MIBC than in non-muscle-invasive bladder cancer (NMIBC), with a strong correlation between SH3YL1 and NOX4 (r = 0.62) in MIBC, suggesting a subtype-specific interaction. Kaplan–Meier survival analysis using The Cancer Genome Atlas bladder cancer (TCGA-BLCA) data further demonstrated that low SH3YL1 expression is significantly associated with poor overall and disease-specific survival in MIBC patients, reinforcing its role as a prognostic biomarker. In conclusion, SH3YL1 is a promising biomarker for identifying the invasive characteristics of MIBC and predicting patient outcomes. These findings underscore the importance of SH3YL1–NOX4 pathways in MIBC and suggest the need for further research into targeted biomarkers for bladder cancer progression and cisplatin-induced AKI to improve patient outcomes in high-risk cases. Full article

Background/Objectives: Delta-radiomics involves analyzing feature variations at different acquisition time-points. This study aimed to assess the utility of delta-radiomics feature analysis applied to contrast-enhanced (CE) and non-contrast-enhanced (NE) T1-weighted images (WI) in predicting the therapeutic response to chemoradiotherapy (CRT) in patients diagnosed with muscle-invasive bladder cancer (MIBC). Methods: Forty-three patients with non-metastatic MIBC (cT2–4N0M0) who underwent partial or radical cystectomy after induction CRT were, retrospectively, reviewed. Pathological complete response (pCR) to CRT was defined as the absence of residual viable tumor cells in the cystectomy specimen. Identical volumes of interest corresponding to the index bladder cancer lesions on CE- and NE-T1WI on pre-therapeutic 1.5-T MRI were collaboratively delineated by one radiologist and one urologist. Texture analysis was performed using “LIFEx” software. The subtraction of radiological features between CE- and NE-T1WI yielded 112 delta-radiomics features, which were utilized in multiple machine-learning algorithms to construct optimal predictive models for CRT responsiveness. Additionally, the predictive performance of the radiomics model constructed using CE-T1WI alone was assessed. Results: Twenty-one patients (49%) achieved pCR. The best-performing delta-radiomics model, employing the “Extreme Gradient Boosting” algorithm, yielded an area under the receiver operating characteristic curve (AUC) of 0.85 (95% confidence interval [CI]: 0.75–0.95), utilizing four signal intensity-based delta-radiomics features. This outperformed the best model derived from CE-T1WI alone (AUC: 0.63, 95% CI: 0.50–0.75), which incorporated two morphological features and one signal intensity-based radiomics feature. Conclusions: Delta-radiomics analysis applied to pre-therapeutic CE- and NE-MRI demonstrated promising predictive ability for CRT responsiveness prior to treatment initiation. Full article

Background/Objectives: The aim of this study was to identify response prediction and prognostic biomarkers in muscle-invasive bladder cancer (MIBC) patients undergoing neoadjuvant chemotherapy (NAC). Methods: A retrospective multicentre study including 191 patients with MIBC who received NAC previous to radical cystectomy (RC) between 1996 and 2013. Gene expression patterns were analysed in 34 samples from transurethral resection of the bladder (TURB) using Illumina microarrays. The expression levels of 45 selected differentially expressed genes between responders and non-responders to NAC were validated by quantitative PCR in an independent cohort of 157 patients. Regression analysis was used to identify predictors of downstaging and relapse. A nomogram for predicting downstaging and relapse—including clinicopathological and gene expression variables—was developed. Results: The expression levels of 1352 transcripts differed between responders and non-responders to NAC. A nomogram based on the most predictive clinical variables (age, Tis (in situ), gender, history of NMIBC, and lymphadenopathy) and genes selected following the Akaike information criterion (AIC) (CBTB16, CHMP6, DDX54, CASP8, LOR, and PLEC) was then created. In addition, a three-gene expression prognostic model to predict tumour relapse was generated. This model was able to discriminate between two groups of patients with a significantly different probability of tumour relapse (HR: 2.11; CI: 1.16–3.83, p = 0.01). Conclusions: Our nomogram based on gene expression and clinical data is a useful tool to predict downstaging and tumour relapse after NAC in MIBC patients. Further validation is warranted. Full article

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

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

Background: In salvage cystoprostatectomies (SCPs), rectal injuries can occur at a rate of 1% to 10%. Factors including T3 disease and prior pelvic radiation can lead to complications such as bleeding, recurrent wound infections and the need for colonic diversion. Methods: We present a male patient in his late 70s with a new diagnosis of pT2 muscle-invasive bladder cancer (MIBC). This is on a background of Stage IIB prostate cancer 10 years ago, managed with external beam radiotherapy. He patient had hyaluronic acid (HA) rectal spacer infiltration into the Denonvilliers’ space two weeks prior, for rectal protection. HA rectal spacers are easily identifiable due to their anechoic appearance on ultrasound imaging, making them easily distinguishable when injected into the Denonvilliers’ space intraoperatively. Results: The patient did not experience any symptoms related to rectal injury and had full bowel continence postoperatively. Conclusion: Although approved for use in radiation treatment for prostate cancer, their role in aiding dissection during SCP remains unexplored. We exhibit the use of HA rectal spacers for rectal protection during SCP. Full article

Background/Objectives: Bladder cancer is a significant clinical problem with approximately 500,000 new cases worldwide annually. In approximately 25% of cases, disease is diagnosed at a stage of invasion of the muscle layer of the bladder. The current standard approach in this disease is preoperative chemotherapy followed by radical cystectomy. Dose-dense MVAC (ddMVAC), a two-day chemotherapy regimen, is the reference treatment protocol in this setting. The presented study evaluated the effectiveness and safety of accelerated MVAC (aMVAC) chemotherapy—a one-day regimen given before the resection of the bladder due to muscle-invasive disease. Methods: A retrospective analysis included 119 consecutive patients diagnosed with urothelial muscle-invasive bladder cancer (MIBC) who underwent preoperative chemotherapy with the aMVAC regimen. The planned treatment included 4–6 cycles of preoperative chemotherapy. The analysis of the degree of histopathological response to treatment was based on the three-grade TRG (tumor regression grade) classification. Results: A complete pathological response (TRG1) was observed in 44 patients (36.7%), and a major pathologic response (<ypT2) was achieved in 58 patients (48.7%). A reduction in the cisplatin dose was associated with a statistically significant decrease in the chance of achieving complete pathologic responses (46.1% vs. 10%, RR for TRG1 = 0.69, p = 0.00118). Patients who received at least 4 cycles (compared to ≤3 cycles) of neoadjuvant chemotherapy had a significantly higher chance of achieving a pathological response (partial or complete) to treatment (78.1% vs. 52.2%, RR 0.68, p = 0.0374). Administration of at least five cycles of chemotherapy was associated (compared to four cycles) with a significantly higher likelihood of achieving a complete pathological response (63.2% vs. 33.8%, RR = 1.71, p = 0.0221). The vast majority of adverse events were in grades 1 and 2, according to CTCAE version 5.0. Only five patients experienced grade 3–4 toxicities. The most common adverse event was anemia, which occurred in 66.3% of patients. Conclusions: Our real-world data analysis confirms the activity, safety, and feasibility of the aMVAC regimen as neoadjuvant chemotherapy in patients with urothelial MIBC. Full article

Background: Immunotherapy is gaining great relevance in both non-muscle-invasive bladder cancer (NMIBC), with the use of bacille Calmette–Guerin (BCG), and in muscle-invasive BC (MIBC) with anti-checkpoint therapies blocking PD-1/PD-L1, CTLA-4/CD80-CD86, and, more recently, NKG2A/HLA-E interactions. Biomarkers are necessary to optimize the use of these therapies. Methods: We evaluated killer-cell immunoglobulin-like receptors (KIRs) and HLA-I genotyping and the expression of NK cell receptors in circulating T and NK lymphocytes at diagnosis in 325 consecutive BC patients (151 treated with BCG and 174 treated with other therapies), as well as in 648 patients with other cancers and 973 healthy donors as controls. The proliferation and production of cytokines and cytotoxicity were evaluated in peripheral blood mononuclear cells, stimulated in vitro with anti-CD3/CD28 or BCG, from selected patients based on HLA-B −21M/T dimorphism (NKG2A ligands). Results: The HLA-B −21M/T genotype showed opposing results in BC patients treated with BCG or other therapies. The MM genotype, compared to MT and TT, was associated with a longer 75th-percentile overall survival (not reached vs. 68.0 ± 13.7 and 52.0 ± 8.3 months, p = 0.034) in BCG, but a shorter (8.0 ± 2.4 vs. 21.0 ± 3.4 and 19.0 ± 4.9 months, p = 0.131) survival in other treatments. The HLA-B −21M/T genotype was an independent predictive parameter of the progression-free survival (HR = 2.08, p = 0.01) and the OS (HR = 2.059, p = 0.039) of BC patients treated with BCG, together with age and tumor histopathologic characteristics. The MM genotype was associated with higher counts of circulating CD56^bright, fewer KIR2DL1/L2⁺ NK cells, and lower NKG2A expression, but not with differential in vitro NK cell functionality. Conclusions: The HLA-B −21M/T is independently associated with BC patient outcomes and can help to optimize the use of new immunotherapies in these patients. Full article

Gender differences in prevalence, tumor invasiveness, response to treatment, and clinical outcomes exist in different types of cancer. The aim of this article is to summarize the sex disparities in bladder cancer diagnosis and treatment and try to suggest areas for improvement. Although men are at a higher risk of developing bladder tumors, women tend to be diagnosed with more advanced stages at diagnosis and are more likely to present with upfront muscle-invasive disease. Non-urothelial histological subtypes are more frequently reported in women. Regarding non-muscle-invasive bladder cancer (NMIBC), several studies have shown that women have a higher risk of disease recurrence after treatment with Bacillus Calmette–Guerin, due to different immunogenicities. In localized muscle-invasive bladder cancer (MIBC), neoadjuvant chemotherapy and cystectomy are less likely to be performed on women and sexual-sparing procedures with neobladder diversion are rarely offered. Finally, women appear to have a poorer prognosis than men, potentially due to the sex-associated intrinsic features of hosts and tumors that may drive differential therapeutic responses, particularly to immune-based therapies. Women are also more likely to develop severe adverse events related to systemic therapies and are underrepresented in randomized studies, leading to a gap between the real world and trials. In conclusion, studies investigating the role of sex and gender are urgently needed to improve the management of urothelial carcinoma. Full article

Bladder cancer (BC) currently ranks as the 9th most common cancer worldwide. It is characterised by very high rates of recurrence and metastasis. Most cases of BC are of urothelial origin, and due to its ability to penetrate muscle tissue, BC is divided into non-muscle-invasive BC (NMIBC) and muscle-invasive BC (MIBC). The current diagnosis of BC is still based primarily on invasive cystoscopy, which is an expensive and invasive method that carries a risk of various complications. Urine sediment cytology is often used as a complementary test, the biggest drawback of which is its very low sensitivity concerning the detection of BC at early stages, which is crucial for prompt implementation of appropriate treatment. Therefore, there is a great need to develop innovative diagnostic techniques that would enable early detection and accurate prognosis of BC. Great potential in this regard is shown by epigenetic changes, which are often possible to observe long before the onset of clinical symptoms of the disease. In addition, these changes can be detected in readily available biological material, such as urine or blood, indicating the possibility of constructing non-invasive diagnostic tests. Over the past few years, many studies have emerged using epigenetic alterations as novel diagnostic and prognostic biomarkers of BC. This review provides an update on promising diagnostic biomarkers for the detection and prognosis of BC based on epigenetic changes such as DNA methylation and expression levels of selected non-coding RNAs (ncRNAs), taking into account the latest literature data. Full article