Background Guidelines recommend intravesical Bacillus Calmette-Guérin (BCG) as adjuvant therapy for intermediate- and high-risk non-muscle-invasive bladder cancer after transurethral resection. In the event of BCG failure, hyperthermic intravesical chemotherapy (HIVEC) represents a treatment alternative to patients who are surgically inoperable, or decline radical cystectomy. Objective The aim of this study was to evaluate oncological outcomes in patients receiving epirubicin-based HIVEC as a second-line therapeutic approach. Methods Retrospective inclusion of patients from our prospectively maintained, multicenter HIVEC database, who underwent HIVEC due to recurrent or persistent high-grade NMIBC following adequate BCG therapy (BCG failure) between November 2016 and December 2024. Survival was evaluated using Kaplan–Meier analysis and log-rank testing. Associations between clinicopathological factors and oncological outcomes were assessed using Cox regression analysis. Results Sixty-five patients were included. Median follow-up was 38 months (IQR 21–55). Twenty-four patients (36.9%) experienced intravesical recurrence with a median intravesical recurrence-free survival (RFS) of 24 months (IQR 9-45) and 1-/2-year intravesical RFS rates of 77.9% and 64.1%, respectively. Extravesical recurrence was observed in 21 patients (32.3%) with a median extravesical RFS of 22 months (IQR 7-43) and 1-/2-year extravesical RFS rates of 81.3% and 70.9%, respectively. Higher number of recurrences prior to HIVEC were significantly associated with extravesical recurrence in univariate (HR 2.23; 95% CI 1.23-3.87; p=0.019) and multivariate analysis (HR 1.31; 95% CI 1.03-1.67; p=0.027). Conclusions Although limited by the relatively small sample size, Epirubicin-based HIVEC demonstrated promising oncological outcomes indicating its potential value as bladder-preserving treatment option after BCG failure. Prospective controlled studies are warranted to further assess the role of epirubicin-based HIVEC in this setting.
Background Large animal models of bladder cancer are lacking. Objective This study aimed to develop and characterize a transgenic porcine model of bladder cancer (BC) using Oncopigs expressing Cre-inducible KRAS G12D and TP53 R167H mutations. Methods Eleven female Oncopigs underwent tumor induction via three cystoscopic inoculation procedures: Procedure I (N = 3, 1 inoculation/pig), chemical dissolution of the glycosaminoglycan layer with N-Dodecyl-β-d-Maltoside DDM followed by adenoviral Cre-recombinase (AdCre) instillation; Procedure II (N = 4, 3 inoculation/pig), mechanical mucosal denudation followed by AdCre instillation; and Procedure III (N = 4, 3 inoculation/pig), cystoscopy-guided submucosal injection of AdCre. Animals were clinically monitored throughout follow-up (14–28 days). Tumor development was assessed on cystoscopy and ultrasonography, and pathologically, immunohistochemically (IHC), and genomically characterized. Results All pigs remained clinically healthy. Tumors developed at 59% (16/27) of inoculation sites: nine (33%) were neoplastic and seven (26%) were inflammatory. Procedure I achieved 100% neoplastic tumors and produced both non-muscle invasive (71%) and muscle-invasive (29%) tumors. Procedure II achieved 50% neoplastic tumors, all of which were muscle invasive (100%). Procedure III generated only inflammatory tumors. Histologically, neoplastic tumors were pathologically interpreted as urothelial cell carcinomas with sarcomatoid differentiation, with IHC confirming the presence of both epithelioid and sarcomatoid features with abundant mixed leukocytic infiltrates. Genomic analyses verified Cre-induced alterations alongside other mutations seen in human BC. Conclusions We herein demonstrate an efficient and reproducible method for developing autochthonous neoplastic bladder tumors in Oncopigs that resemble human bladder cancer of varying stages. This large animal model facilitates the evaluation of novel surgical and intravesical therapies in BC.
Background Urothelial bladder cancer exhibits marked molecular and clinical heterogeneity. While genomic and transcriptomic profiling of muscle-invasive bladder cancer (MIBC) has revealed recurrent alterations with therapeutic and prognostic relevance, limited access to molecular testing constrains clinical use. Computed tomography (CT), routinely performed for staging and surveillance, may serve as a noninvasive adjunct for tumor biology. Radiomics, the quantitative extraction of imaging features, offers a means to associate imaging phenotypes with molecular characteristics. Methods Genomic data for The Cancer Genome Atlas were integrated with CT images from the Cancer Imaging Archive for 89 patients with biopsy-proven MIBC. An in-house radiomics pipeline extracted 488 texture metrics characterizing the brightness distribution, pixel relationships, and spatial patterns of segmented tumors. Three classifiers - Random Forest, Extreme Gradient Boosting, and Elastic Net - were trained to predict DNA mutations, tumor mutational burden (TMB), and mRNA expression. Model performance was evaluated using 10-fold cross-validation. Results Among 15 recurrent mutations, EP300, FGFR3, and ARID1A were predicted most reliably (AUCs = 0.77, 0.76, 0.75). Models identified high-TMB tumors (AUC = 0.61), poor-prognosis transcriptomic signatures (AUC = 0.73, 0.65), expression of key cell cycle (CKDKN1A, AUC = 0.78) and apoptotic (CASP3, AUC = 0.71) genes, and discriminated the luminal infiltrated molecular subtype from other variants (AUC = 0.69). Conclusion Our study demonstrates that CT-derived radiomics features can capture biologically and clinically relevant information in muscle-invasive bladder cancer. These findings support the potential utility of radiomics as a noninvasive, scalable adjunct to genomic profiling in MIBC.
Non-muscle invasive bladder cancer (NMIBC) is a biologically and clinically heterogeneous disease, accounting for approximately 75% of bladder cancer cases. Over the past decade, multiple RNA-based molecular classification systems for NMIBC have been proposed, demonstrating associations with tumor stage, grade, prognosis, and treatment response. However, unlike muscle-invasive bladder cancer, a unified consensus classification for NMIBC is lacking, limiting clinical translation and cross-study comparability. To address this gap, the first NMIBC Consensus Classification Meeting was convened in November 2024 at Erasmus University Medical Center, bringing together 13 international experts from seven countries representing major NMIBC molecular classification efforts. This report summarizes the discussions, comparative evaluation of existing classification systems, and the agreed strategy towards developing a consensus molecular model. The meeting focused on harmonizing heterogeneous transcriptomic datasets, integrating RNA sequencing and microarray platforms, and assessing the applicability of classification models across tumor stages (Ta/T1) and grades. Key features, strengths, and limitations of the Lund Taxonomy, Leeds, Birmingham, UROMOL, and Rotterdam (BCG response) subtypes were critically examined. Building on prior experience from the muscle-invasive bladder cancer consensus, participants agreed on a centroid-based clustering framework using rigorously defined core samples to derive stable consensus subtypes and a single-sample classifier with associated probability scores. A large, curated dataset encompassing approximately 2500 NMIBC samples from published cohorts will facilitate model development and validation. The resulting consensus classification aims to improve biological understanding, facilitate reproducibility across studies, and enable future evaluation of prognostic and therapeutic relevance, including response to intravesical BCG therapy.
Background Concomitant carcinoma in situ (CIS) with high-grade papillary urothelial carcinoma impacts patient risk stratification and treatment. However, on identification of a high-grade papillary lesion, pathologists may be disinclined to search for possible CIS. Several newer agents for bacillus Calmette-Guérin–unresponsive non–muscle-invasive bladder cancer (NMIBC) are indicated specifically for patients with CIS ± papillary tumors; hence failure to detect/report CIS may limit treatment options. Objective To assess CIS frequency in patients with high-grade Ta/T1 NMIBC. Methods In this retrospective cohort study, transurethral resection of bladder tumor biopsy specimens with an accompanying diagnosis of high-grade papillary NMIBC without CIS were identified in the PathNet database (2023–2024) and re-reviewed by a single pathologist for the presence of concomitant CIS. Results In total, 316 cases of high-grade papillary urothelial carcinoma (254 Ta, 62 T1 disease) were identified for re-review. Mean patient age was 73 (range 27–93) years; 81.0% of patients were male. On re-review, CIS was identified in 80 cases (25.3%, 95% CI 20.8%–30.4%). CIS frequency was higher in T1 disease (19/62 cases [30.6%]) vs Ta disease (61/254 cases [24.0%]). Among the 8 pathologists who performed the initial review, CIS-positivity rates in their individual biopsy samples varied from 15.0% (6/40) to 66.7% (2/3). Conclusion This study suggests that ∼25% of patients with high-grade papillary urothelial carcinoma may have unreported CIS. Close communication between the urologist and pathologist is crucial in ensuring specific exclusion of CIS in all bladder specimens, since a diagnosis of concomitant CIS may impact patient management.
Background:The latest bladder cancer (BC) urine tests based on multiple genomic and/or epigenomic markers detect BC with high sensitivity and specificity. The GALEAS Bladder (GB) gene panel covers several actionable mutations, including in FGFR3. Objective:To modify GB to detect FGFR3 fusions as well as single nucleotide variants and assess its potential as a urine-based companion diagnostic. We also study tissue-urine concordance and associations between FGFR3 genomic alterations and FGFR3 expression. Methods:Probes were added to GB covering the 3'-region of FGFR3. The new panel was used to analyse genomic DNA extracted from 158 frozen primary BCs. Mutation concordance was also analysed in 107 tumour-urine pairs. Associations between FGFR3 mutations and expression were analysed in 608 FFPE BCs with the Decipher Bladder transcriptome assay. Results and limitations:FGFR3-TACC3 fusions were found in 3/3 positive controls and 4/158 frozen BCs. Fusions were also detectable in genomic DNA from FFPE tumour and urine cell pellet DNA. All fusions were corroborated by PCR and Sanger sequencing. FGFR3 mutation status in urine was 94.4% concordant (95% CI 87.7-97.7%); GB detected mutations in urine with 92.1% sensitivity (95% CI 81.7-97.0%) at 97.7% specificity (95% CI 86.5-99.9). All FGFR3 mutations were associated with increased FGFR3 expression. This is a proof-of-principle study, rather than definitive evidence of utility as a companion diagnostic, with the need for fusion detection validation in larger patient cohorts. Conclusions:In addition to BC detection, a modified version of GB demonstrates feasibility for tissue and urine-based detection of FGFR3 fusions.
Background Neoadjuvant chemotherapy followed by radical cystectomy (NACT-RC) is the prevailing standard of care for muscle-invasive bladder cancer (MIBC), but trimodality treatment (TMT) using chemoradiation after transurethral resection of bladder tumor (TURBT) is an effective alternative in select patients. Objective This study examined patterns of care and impact of social determinants of health on the overall survival (OS) using the National Cancer Database (NCDB). Methods Data on patients aged ≥18 years with stage II-IIIA MIBC treated with TMT or NACT-RC during 2014–2021 were analyzed with propensity score matching. Logistic and Cox regression were used to evaluate the association of social determinants of health with patterns of care and OS. Results Among 18,072 cases (mean age 68.3 years), 77.1% received NACT-RC. TMT use increased from 18.4% in 2014 to 27.1% in 2021 (p < 0.001). The odds for receiving NACT-RC were higher for patients with stage IIIA (odds ratio (OR) = 1.21, 95% confidence interval (CI) 1.09-1.34). However, older patients (OR 0.86, 95% CI 0.87-0.88), those treated at comprehensive community cancer programs (OR 0.51, 95% CI: 0.46-0.55), or used Medicaid (OR = 0.48, 95% CI 0.39-0.61) had lower odds for receiving NACT-RC. In propensity score matching analysis, NACT-RC was associated with lower mortality compared to TMT (Hazard ratio (HR) = 0.66, 95% CI:0.59-0.73). Medicaid users receiving NACT-RC had the highest mortality risk (HR = 1.47, 95% CI:1.28-1.68, p interaction =0.001). Conclusion TMT for MIBC has increased in recent years. Selection between NACT-RC and TMT was influenced by age, stage, diagnosis year, comorbidities, travel distance, facility, and insurance type, highlighting disparities in MIBC treatment. Categories Radiation Oncology, Oncology
Enfortumab vedotin with pembrolizumab (EV + pembro) has transformed first-line treatment of advanced urothelial carcinoma (aUC). No prospective data are available evaluating outcomes of different therapies following progression on EV + pembro. Patients who received first-line EV + pembro and had second-line therapy data available were eligible and included. Second-line treatment types were categorized as cisplatin-based therapy, carboplatin-based therapy, EV rechallenge, or other. Outcomes assessed included real-world overall survival (rwOS) and real-world time to next therapy (rwTTNT). Among 15,236 pts with aUC, 757 received first-line EV + pembro, and 118 who went on to second-line therapy and had survival outcomes were included. Second-line treatments were carboplatin-based (35%), cisplatin-based (13%), other regimens (38%), and EV rechallenge (13%). The “Other” category included erdafitinib, trastuzumab deruxtecan, and sacituzumab govitecan. Median rwTTNT ranged from 3–4.7 months for platinum regimens to 8.5 months with EV rechallenge. Median rwOS ranged 7.1–8.5 months for platinum-base therapy or EV rechallenge and 14 months for other regimens. This is the largest real-world study to date evaluating real-world treatment patterns and outcomes with various second-line therapies after progression on first-line EV + pembro in aUC. Median rwOS and rwTTNT were modest across all treatment groups. These findings underscore the limited efficacy of current second-line options in the post EV + pembro setting.
Background Sarcopenia is increasingly recognized as an imaging-based prognostic factor in various cancers, but its gender-specific radiological indicators in bladder cancer patients undergoing radical cystectomy are not well defined. Objective The aim of this study was to identify the radiological sarcopenia parameters that can be used to predict overall survival(OS) in patients who underwent radical cystectomy(RC). Methods The data of a total of 183 patients who underwent RC for urothelial bladder cancer and had an abdominal computed tomography(CT) scan within three months prior to surgery, were retrospectively analyzed. Skeletal muscle areas at the L3 vertebral level and average Hounsfield unit(HU) measurements were extracted from the CT images.Based on these measurements, five sarcopenia-related parameters [skeletal muscle index (SMI) type 1, SMI type 2, psoas muscle index(PMI) type 1, PMI type 2, and skeletal muscle density(SMD)] were calculated and investigated their prognostic effect on OS using uni- and multi-variable Cox regression analysis. Results The median follow-up period was 22 months(IQR: 10–50).In univariate Cox regression analysis, significant factors affecting overall survival in men included age, pT stage, pN stage, SMI type 1, SMI type 2, and PMI type 2(p < 0.05).In women, significant factors included pT stage, pN stage, and only SMD(p < 0.05).Among radiologic sarcopenia markers, multivariate Cox regression models indicated that significance of the SMI type 1, the SMI type 2 and the PMI type 2 remained as prognostic factors for overall survival in men(p < 0.05). In women, only SMD remained significant(p = 0.018). Conclusions Our analysis highlighted that gender-specific radiological sarcopenic parameters impact on OS among patients undergoing RC.SMI type 1, SMI type 2, and PMI type 2 for male and only SMD for female were prognosticators in patients undergoing RC.
Background:Radical cystectomy (RC) with urinary diversion remains the standard of care for muscle invasive bladder cancer. While metabolic acidosis (MA) after RC is common, the relationship between MA, post-operative complications, and the impact of bicarbonate supplementation remains unclear. Objective:To review the role of bicarbonate therapy for MA following RC. Methods:We performed a comprehensive systematic review according to Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines analyzing MA after RC. We included randomized controlled trials and cohort studies that reported metabolic acidosis complications and studies that utilized bicarbonate therapy peri-operatively. Our primary outcome was metabolic acidosis or role of metabolic acidosis as it relates to bicarbonate therapy or post-operative complications. Results:Twenty-nine studies were identified to investigate MA in the setting of postoperative complication rates or the role of bicarbonate treatment in peri-operative pathways. 19 studies evaluated the incidence of MA without intervention, 5 studies supplemented bicarbonate therapy for patients meeting specific criteria, and 5 studies utilized a standardized postoperative bicarbonate therapy regimen. The incidence of post-operative metabolic acidosis ranged from 1-86% after continent urinary diversion and 1-27% after ileal conduit urinary diversion. Post-operative renal function, diabetes, and older age were factors associated with metabolic acidosis. There was lack of uniformity, indications, or consistent outcomes for utilizing postoperative bicarbonate therapy. Conclusion:There is little uniformity regarding the role of supplemental bicarbonate therapy and its impact on post-operative complications following urinary diversion. Future studies are needed to better evaluate the role MA plays in peri-operative RC pathways.
Background Gene polymorphisms can lead to differential production of inflammatory proteins associated with cancer development. Prior explorations of the association of single nucleotide polymorphisms (SNPs) of monocyte chemoattractant protein (MCP-1/CCL2) and its receptor, CCR2, to bladder cancer, yielded conflicting findings.Objective To analyze the distributions of the polymorphisms CCL2 rs1024611 and CCR2 rs1799864 between healthy controls and bladder cancer patients to determine if they are associated with bladder cancer risk in a cohort of Hispanic White and non-Hispanic White men.Methods DNA was isolated from blood obtained from healthy male controls (CCL2 n = 447; CCR2 n = 612) and from male bladder cancer patients (CCL2 n = 233; CCR2 n = 227). The CCL2 rs1024611 SNP and CCR2 rs1799864 SNP were genotyped using the TaqMan methodology. Multivariable logistic regression was used to determine associations between SNP genotypes and bladder cancer in Hispanic and non-Hispanic White men.Results There were no significant differences in the genotype frequencies for either the CCL2 or CCR2 SNP and bladder cancer risk was equivalent regardless of CCL2 (NHW AA vs AG/GG, p = 0.7232; H AA vs. AG/GG, p = 0.5187) or CCR2 genotype (NHW AA vs GG/GG, p = 0.6826; H GG vs. AA/AG, p = 0.2425).Conclusion Prior studies have shown conflicting results regarding the association between bladder cancer risk and the CCL2 rs1024611 and CCR2 rs1799864 polymorphisms. We were unable to validate significant findings regarding any relationship between these polymorphism distributions across individuals with or without bladder cancer in a cohort of non-Hispanic White and Hispanic White men, suggesting no role of CCL2/CCR2 polymorphisms in bladder cancer.
Background:Metastasis-directed therapy (MDT) for oligometastatic cancer is utilized for genitourinary malignancies including prostate and kidney cancers. Clinical research on MDT for urothelial carcinoma (UC) remains sparse, especially as systemic therapy advances have improved outcomes. Objective:We investigated the role of MDT, specifically radiotherapy, for patients with oligometastatic bladder or upper-tract UC. Methods:Data were collated on patients with metastatic UC with 5 or fewer metastatic sites undergoing MDT with ablative radiotherapy with or without preceding systemic therapy during January 2016 to July 2024. Endpoints were progression-free survival (PFS), and overall survival (OS). Cox proportional hazards analysis was conducted to determine the covariates associated with these endpoints. Results:Fifty-two patients were included. Most were men (67%). Median age was 68 years (interquartile range, 62-78). Most had bladder primary tumors (79%). Patients had a median of 1 metastatic site. Most received ≥2 lines of systemic therapy before MDT (60%), whereas 8% received no systemic therapy before MDT. MDT was delivered to all metastases in 71% of cases, whereas the remaining cases (29%) had MDT delivered to select sites. Median follow-up from the diagnosis of metastasis was 32 months (interquartile range, 23-42). Median PFS and OS were 19 months (95% CI, 15-24) and 42 months (95% CI, 24-60), respectively. Conclusions:MDT may serve as an effective adjunct to systemic therapy to improve outcomes of oligometastatic and oligoprogressive UC.
Introduction:Radical cystectomy or trimodal therapy are treatment options for non-metastatic bladder cancer. However, there is limited evidence guiding post-treatment follow-up regimens, resulting in variations in care. Objective:A Swiss consensus meeting aimed to identify gaps in follow-up strategies and subsequently tailoring follow-up protocols after curative treatment for bladder cancer. Methods:A consensus meeting including participants from urology, oncology, radiation oncology, neuro-urology, international advisors, and patient representatives was held. 19 pre-formulated questions addressing follow-up duration, frequency, and modalities after radical cystectomy or trimodal therapy for bladder cancer were discussed and voted by participants. Results:42 experts from 22 institutions participated in the meeting. Agreement was reached on several important elements of oncological and functional follow-up like risk-adapted follow-up and regular usage of patient reported outcome measures (PROMs) and 3 novel personalized follow-up schedules were suggested, balancing oncological surveillance, and monitoring functional complications. Conclusion:We agreed on 3 newly developed Swiss follow up schedules for patients with bladder cancer who underwent cystectomy or trimodal therapy with curative intent; these protocols include stage-specific recommendations for type and timing of investigations to detect relapse combined with balanced measures to monitor functional complications such as PROMS and specific clinical examinations. These protocols will be evaluated in a prospective national multicentric cohort study.
Background:In vivo modeling is essential to study bladder cancer biology. Orthotopic bladder tumor models involve direct introduction of tumor cells into the bladder of a laboratory animal. Common techniques for orthotopic tumor introduction include transurethral, ultrasound-guided, or surgical approaches. Objective:We systematically collected data from published studies that have utilized orthotopic bladder tumor models in mice or rats to identify trends and outcomes across techniques. We used these data to optimize a surgical orthotopic technique. Methods:A PubMed search was performed to identify articles involving orthotopic implantation of tumor cells into mouse or rat bladders for research purposes. Results were individually reviewed and filtered. All studies reporting preclinical models established via a surgical, transurethral, and/or ultrasound-guided approach were included. Surgical orthotopic tumor implantation experiments were performed and data collected. Results:A total of 254 studies were identified, of which 187 met criteria and were included in the analysis. Data regarding each orthotopic technique was reviewed and trends were identified. Transurethral installation was the most commonly used method but had the lowest tumor take rate. The surgical approach had the highest metastatic rate. These data were used to inform optimization of the surgical orthotopic approach in our laboratory. The study is limited by its retrospective design and heterogeneity of data reporting across studies. Conclusions:Tumor take rates vary across orthotopic implantation techniques. Optimization of a surgical implantation approach is feasible. These findings can inform best practices for orthotopic bladder cancer models.
Background Neighborhood Deprivation (ND) indices serve as indicators of socioeconomic status and are recognized determinant of survival across multiple cancer types. Objective To determine the potential effect of ND on urothelial bladder cancer survival outcomes using a California-specific measure, the Healthy Places Index (HPI). Methods We queried our institutional database for patients who underwent radical cystectomy from 2013 to 2019. Patients were categorized into HPI quartiles based on their residential areas, with Q1 representing the most disadvantaged and Q4 the least disadvantaged. Multivariable logistic regression was used to identify predictors of adverse pathological features. Multivariable cox regression was utilized to evaluate the association of HPI with overall survival (OS) and recurrence free survival (RFS). Results A total of 729 patients were included in our analysis. Belonging to the most disadvantaged quartile (Q1) was associated with higher odds of lymphovascular invasion (HR 1.94, p < 0.001), and extravesical disease (HR 1.87, p < 0.001) at presentation, compared to the least deprived quartile (Q4). Survival analyses showed that worse ND was independently associated with worse OS (Q1 vs Q4: HR: 1.76, 95% CI: 1.18–2.62, p = 0.006) after adjusting for age, extravesical disease, node-positivity, and lymphovascular invasion. OS was positively associated with the education, economic, and transportation subdomains of HPI in univariable analyses. Conclusions Greater ND is associated with adverse pathology on presentation and worse OS following radical cystectomy for UBC. Larger prospective studies are warranted to further assess the influence of social disparities on survival outcomes following RC.
Background: Recently, urinary extracellular vesicles (uEVs) have emerged as promising biomarkers for early diagnosis, prognosis, and treatment monitoring in urothelial carcinoma (UC). uEVs encapsulate nucleic acids, proteins, and other bioactive molecules that reflect the tumor microenvironment, potentially offering a non-invasive approach for real-time cancer assessment. Methodology: A comprehensive literature review was conducted, focusing on recent studies evaluating uEVs in UC, particularly regarding their molecular contents, such as microRNA (miRNA), long non-coding RNAs (lncRNAs), circular RNA (circRNA), messenger RNA (mRNA), and proteins. Studies that assessed the clinical utility of uEVs for diagnosis, prognosis, and individualized treatment guidance in UC were emphasized. Results: Studies have identified a variety of EV-RNAs and EV-proteins as potential diagnostic and prognostic biomarkers, with some showing promise for treatment response. However, challenges in validation, limited cohort sizes, and inconsistent findings have hindered their clinical application. Liquid biopsies using uEVs are advancing UC precision medicine by improving diagnostic accuracy, identifying molecular subtypes, and potentially predicting therapeutic responses. Conclusions: UEVs are promising for UC management, offering a minimally invasive, accessible source of biomarkers for diagnosis, prognosis, and treatment monitoring. Although further research and large-scale validation are needed, the integration of uEVs into clinical practice has the potential to transform UC patient care by providing precise personalized management strategies. Continued advances in EV research and biomarker discovery may ultimately lead to more effective targeted UC therapies.
