Muscle-invasive bladder cancer (MIBC) is an aggressive urological malignancy characterized by a profoundly immunosuppressive tumor microenvironment (TME) driven by dysregulated oncogenic metabolism. The oxidoreductase NAD(P)H:quinone oxidoreductase 1 (NQO1) stabilizes the core metabolic regulator hypoxia-inducible factor 1α (HIF-1α), which further transcriptionally activates the homeobox transcription factor SIX1, forming a coordinated NQO1/HIF-1α/SIX1 signaling axis that drives metabolic reprogramming and immune evasion in MIBC, yet targeted therapies disrupting this metabolic-immune nexus remain clinically unavailable. Here, we developed a biomimetic macrophage membrane-cloaked nanoplatform (MMP@siN/NC) for targeted co-delivery of NQO1-targeting siRNA (siNQO1) and the SIX1 small-molecule inhibitor NCGC, with a PEG-PDLLA/DOTAP hybrid core enabling prolonged systemic circulation, enhanced tumor targeting, efficient cellular internalization, facilitated endosomal escape, and synergistic drug release. In vitro, MMP@siN/NC exerted robust cytotoxicity against MIBC cells, induced potent immunogenic cell death (ICD), and suppressed aerobic glycolysis and tricarboxylic acid (TCA) cycle flux via axis blockade, which further promoted dendritic cell maturation, M1 macrophage polarization, and tumor-specific T-cell priming. In vivo, MMP@siN/NC potently inhibited tumor growth, elicited a systemic abscopal effect, and established durable anti-tumor immune memory in subcutaneous MIBC models, with strong synergistic efficacy in combination with anti-CTLA-4 (αCTLA4) immune checkpoint blockade. Critically, in a clinically relevant orthotopic MIBC model, the nanosystem exhibited excellent tumor accumulation, significant therapeutic efficacy, prolonged survival, and a favorable safety profile. Collectively, this work validated the NQO1/HIF-1α/SIX1 axis as a targetable metabolic-immune driver in MIBC, and presented a translatable nanotherapeutic strategy to simultaneously disrupt tumor metabolism and reactivate anti-tumor immunity for MIBC treatment.

OBJECTIVE:To compare intrarenal pelvic pressure profiles and clinical outcomes between the leg-split-free lateral decubitus position and the conventional lithotomy position during flexible ureteroscopy with a negative-pressure aspiration sheath. METHODS:A prospective study was conducted at Peking University People' s Hospital among patients undergoing unilateral flexible ureteroscopy with a negative-pressure aspiration sheath from January 2024 to December 2025. Participants were allocated into two groups according to surgical positioning: Leg-split-free lateral decubitus group and conventional lithotomy group. An intelligent, pressure- and temperature-controlled flexible ureteroscopy system was employed to continuously monitor intrapelvic pressure and temperature throughout the procedure. The incidence, duration, and clinical implications of intrapelvic hypertension were compared between the two groups. RESULTS:A total of 40 patients were enrolled, 20 in each group. No statistically significant differences were observed between the groups in baseline characteristics, including gender, age, stone diameter, stone number, stone location, or degree of hydronephrosis (all P>0.05). Intraoperative analysis revealed that the duration of intrapelvic hypertension was significantly shorter in the leg-split-free lateral decubitus group than in the lithotomy group [25.0 (0.0, 31.8) s vs. 115.0 (79.8, 176.0) s, P < 0.01]; similarly, the duration of elevated intrapelvic temperature was also significantly reduced [3.0 (2.0, 9.8) s vs. 18.5(16.0, 24.5) s, P < 0.01]. Postoperative follow-up showed no cases of fever in the leg-split-free lateral decubitus group, whereas two patients in the lithotomy group developed fever; however, this difference in febrile complication rate did not reach statistical significance (P=0.15). All the patients underwent computed tomography three months postoperatively to assess stone-free status. The results indicated that the stone-free rate in the leg-split-free lateral decubitus position group was significantly higher than that in the lithotomy position group (P=0.04). CONCLUSION:This prospective exploratory study suggests that compared with the lithotomy position, the leg-free lateral decubitus position may be more conducive to maintaining lower intrapelvic pressure and temperature during the operation and is associated with a higher stone clearance rate postoperatively. However, these findings still need to be verified by large-sample, multi-center, randomized controlled trials.

OBJECTIVE:To investigate the association between preoperative nutritional indicators and survival outcomes in patients with upper tract urothelial carcinoma (UTUC) undergoing radical nephroureterectomy (RNU), and to compare the predictive performance of different nutritional scoring systems. METHODS:A retrospective analysis was conducted on UTUC patients who underwent RNU. Nutritional scores [geriatric nutritional risk index (GNRI), prognostic nutritional index (PNI), controlling nutritional status (CONUT), triglycerides-total cholesterol-body weight index (TCBI)] were calculated. Variables with P < 0.10 in univariable Cox regression were entered into multivariable analysis using backward stepwise selection based on the Akaike Information Criterion (AIC) to identify independent predictors and construct a nomogram. Kaplan-Meier curves with log-rank tests and time-dependent ROC curves were applied for survival analysis. A two-sided P < 0.05 was considered statistically significant. RESULTS:A total of 481 UTUC patients were included. Multivariable analysis identified pathological T3/T4 stage, N1/N2 stage, high World Health Organization/International Society of Urological Pathology (WHO/ISUP) grade, estimated glomerular filtration rate (eGFR), blood transfusion, ureteral management, GNRI, and PNI as independent predictors of overall survival (OS) (P < 0.05). Independent predictors of cancer-specific survival (CSS) included pathological T2-T4 stage, N1/N2 stage, laparoscopic surgical approach, blood transfusion, GNRI, and PNI (P < 0.05). The nomogram constructed based on these independent predictors demonstrated good calibration. Patients with GNRI < 98 or PNI < 52 had significantly shorter OS and CSS (Log-rank P < 0.05). At the end of 60 months, the area under the curve (AUC) values of GNRI and PNI for predicting OS were 0.623 and 0.632, respectively, and for predicting CSS were 0.632 and 0.645, respectively. Time-dependent ROC analysis showed that both indicators had stable predictive performance for CSS, while their predictive ability for OS showed a mild increasing trend over the follow-up time. CONCLUSION:Preoperative GNRI and PNI are independently associated with OS and CSS in patients with UTUC after RNU, demonstrating stable predictive performance across different follow-up periods.

Introduction: Covered metal ureteral stents (CMUSs) have shown promising results for ureteral stricture. However, 3-year outcomes of CMUSs are lacking. This study aimed to evaluate the 3-year efficacy and safety of CMUSs in the maintenance treatment of refractory ureteral stricture (RUS) and explore risk factors for CMUSs-related complications. Methods: Between August 2018 and July 2021, 321 patients (366 renal ureter units [RUUs]) with RUS who underwent CMUSs implantation surgery were prospectively recruited in this study. A regular 3-year follow-up protocol including serum biochemistry test, abdominal imaging, and ureteral stent syndrome questionnaire was established to analyze ureteral patency and patient's quality of life (QoL). The primary ureteral patency was defined as patent ureters without CMUSs-related complications, while secondary ureteral patency also included those that restored patent after endoscopic interventions. Results: The study included 105 (32.7%) patients with stone-related benign ureteral stricture (BUS), 90 (28.0%) with nonstone-related BUS, 76 (23.7%) with radiation-induced ureteral stricture (RIUS), and 50 (15.6%) with malignant ureteral stricture. There existed significant differences in mean serum creatinine levels and renal pelvis widths before and after CMUSs implantation (all p < 0.001). Patients' QoL significantly improved at postoperative 12 and 36 months (both p < 0.001). CMUSs-related complications occurred in 95 (26.0%) RUUs, including 24 (6.6%) with end-stent ureteral restenosis, 28 (7.7%) with stent migration, 31 (8.5%) with stent encrustation, 7 (1.9%) with infection, and 5 (1.4%) with ureteral fistula. The 3-year primary and secondary ureteral patency rate was 74.0% and 90.4%, respectively. However, among patients with RIUS, the primary and secondary ureteral patency rates were only 54.7% and 77.4%, respectively. Conclusion: CMUSs are effective and safe in the 3-year maintenance treatment of RUS. Patients with CMUSs experience long-term improved QoL. However, patients who underwent radiotherapy are susceptible to developing CMUSs-related complications.

OBJECTIVE:To examine the prognostic differences between metachronous and synchronous sporadic bilateral renal cell carcinoma (BRCC). METHODS:This cohort study was conducted in the Surveillance, Epidemiology, and End Results database among patients diagnosed with BRCC between 2004 and 2021. Patients were categorized into synchronous and metachronous groups (synchronous tumors occurred within 6 months of the first RCC diagnosis, while metachronous tumors occurred more than 6 months after the first RCC diagnosis). The propensity score matching (PSM) approach was employed to compare these two groups. Cox's regression analysis evaluated cancer-specific survival (CSS) and overall survival (OS). Interaction, sensitivity, and subgroup analyses were also performed to test the results' robustness. RESULTS:A total of 4694 patients with BRCC were included, with 2710 (57.7%) in the synchronous group and 1984 (42.3%) in the metachronous group. After applying PSM, patient characteristics between the two groups were well balanced. Over a median follow-up of 85 months (interquartile range: 43-132 months), significant differences were noted between the synchronous and metachronous groups in both CSS [hazard ratio (HR) = 2.661, 95% confidence interval (CI): 1.987-3.564, P < 0.001] and OS (HR = 2.481, 95% CI: 2.060-2.988, P < 0.001). Stratified Cox regression accounting for matched pairs indicated poorer CSS (HR = 3.170, 95% CI: 2.081-4.828, P < 0.001) and OS (HR = 2.631, 95% CI: 2.116-3.270, P < 0.001) in the synchronous group. The robustness of these results was supported by multivariate competing risk regression, as well as interaction, sensitivity, and subgroup analyses. CONCLUSIONS:Synchronous BRCC was associated with poorer survival than the metachronous group. These findings may offer important insights for managing patients with BRCC.

Bladder cancer (BCa) is relatively common in patients diagnosed with upper tract urothelial carcinoma (UTUC); however, the impact of BCa history on UTUC prognoses after radical nephroureterectomy (RNU) is unclear. This retrospective, multicenter cohort study aimed to assess this relationship and improve clinical decision making. We conducted a comprehensive analysis of propensity score-matched (PSM) data from two Chinese centers and the Surveillance, Epidemiology, and End Results (SEER) database. Patients were categorized into three groups: BCa-UTUC (defined as patients with a BCa history or BCa occurring within 3 months following RNU); UTUC-BCa (defined as patients who had BCa for 3 months or more following RNU); or solely UTUC (defined as patients with no BCa). Kaplan–Meier analysis and log-rank tests were used to compare survival differences, and Cox’s regression analysis was used to identify risk factors associated with overall survival (OS) and cancer-specific survival (CSS). Overall, 7249 cases were included (1010 from China, 6239 from the SEER database). PSM ensured well-balanced baseline characteristics. In the Chinese cohort, BCa-UTUC cases had significantly poorer CSS than solely UTUC (hazard ratio [HR] 2.334, 95

The purpose of this study was to find out the impact of lymph node dissection (LND) on the prognosis of patients undergoing cystectomy for non-muscle invasive bladder cancer (NMIBC) and determine the minimum number of lymph nodes (LNs) for resection. Patients with NMIBC undergoing cystectomy between 2004 and 2015 were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. Propensity score matching and multivariate Cox regression analyses were performed to mitigate the influence of selection bias and control for potential confounding variables. Of 1950 patients with NMIBC, 1353 underwent LND, of which 58 (4.2

Objective:Many studies have stressed the necessity of repeat transurethral resection (reTURB) following the initial conventional transurethral resection of the bladder for non-muscle invasive bladder cancer (NMIBC) patients. However, there have been few studies focusing on the role of reTURB after en bloc resection of bladder tumor (ERBT) for NMIBC by far. This study aimed to evaluate whether reTURB can be avoided after ERBT. Materials and methods:We conducted research in PubMed, Web of Science, EMBASE, and the Cochrane Library up to November 14, 2024, to identify studies on the reTURB after initial ERBT. For data conversion and the combined calculation of the incidence rate, we utilized R software (R Foundation for Statistical Computing, Vienna, Austria) and Cochrane Review Manager 5.4 (The Cochrane Collaboration, London, UK) along with the double arcsine method. This systematic review protocol was registered at the International Prospective Register of Systematic Reviews (PROSPERO) under number 1082989. Results:A total of 17 studies involving 1051 participants were included. The rates of residual tumor and tumor upstaging detected by reTURB or cystoscopy after ERBT were 9% (95% confidence interval (CI) = 4%-16%) and 0% (95% CI = 0%-1%). No statistically significant positive effect of reTURB after initial ERBT was exhibited in recurrence-free survival (RFS), tumor recurrence, and progression. The pooled hazard ratios of 1-year and 5-year RFS were 0.77 (95% CI = 0.41-1.44, p = 0.41) and 0.83 (95% CI = 0.58-1.20, p = 0.33). The pooled odds ratio of progression and recurrence were 1.13 (95% CI = 0.53-2.41, p = 0.75) and 0.78 (95% CI = 0.53-1.16, p = 0.23). Conclusion:ERBT can successfully regulate the rate of tumor upstaging and residual tumor to an acceptable level. For patients with NMIBC, subsequent reTURB may not be required following the initial ERBT.

To enhance urothelial carcinoma (UC) prognosis, clinicians combine surgery with intraoperative (ICT), neoadjuvant (NACT), or adjuvant chemotherapy (ACT); however, studies on their individual and combined effects vary. Furthermore, studies on the combined use of ACT and NACT are scarce. This study aimed to assess the impact of these chemotherapy regimens on UC prognosis, particularly the effectiveness of ACT + NACT, using the Surveillance, Epidemiology, and End Results (SEER) database. We analyzed 45,211 UC cases from 2019 to 2021, focusing on renal, ureter, bladder, prostate, and urethra UC. Cox model-adjusted survival curves and multivariable Cox regression were performed using SPSS and R software. Compared with ACT, NACT alone did not significantly impact survival (hazard ratio [HR] 0.834, 95

Bladder cancer remains a significant clinical challenge, necessitating the development of innovative therapeutic strategies. Recent advancements have highlighted the potential of reactive oxygen species (ROS)-responsive drug delivery systems in cancer therapy. In this study, we introduce a novel treatment approach utilizing a ROS-responsive camptothecin (CPT) prodrug encapsulated within a chitosan nanocarrier, named CACPT. Cinnamaldehyde (CA), acting as a ROS generator, forms thioketal bonds with CPT to create a prodrug that responds selectively to the elevated ROS levels within the tumor microenvironment. Upon exposure to high ROS conditions, these thioketal bonds are cleaved, resulting in the simultaneous release of CPT and CA. The liberated CA further enhances ROS production, establishing a positive feedback loop that amplifies the therapeutic effect. The use of amphiphilic chitosan nanocarriers enhances the retention and penetration of the prodrug within bladder tissue, optimizing its therapeutic potential. Our experimental findings demonstrate that this self-enhanced ROS-responsive release promotes increased cellular uptake and significantly enhances the anticancer efficacy of CACPT. These results position CACPT as a promising candidate for intravesical therapy in bladder cancer, potentially overcoming current limitations in treatment options. The innovative combination of ROS-responsive mechanisms and chitosan nanocarriers represents a paradigm shift in bladder cancer therapeutics, offering a multifaceted approach with substantial promise for clinical translation.

To evaluate the effects of surgical interventions on individuals diagnosed with bladder neuroendocrine carcinoma (BNEC). Data were gathered from the Surveillance, Epidemiology, and End Results (SEER) database for this retrospective analysis. No-surgery procedures included TURBT, cryotherapy, excisional biopsy, or partial cystectomy. Surgery was categorized as cystectomy, radical cystectomy, or a more complex surgical intervention, such as exenteration. A propensity score overlap weight (PSOW) analysis was performed to adjust statistical influences between the two groups. Prognostic factors related to cancer-specific survival (CSS) and overall survival (OS) were assessed using Cox proportional hazard regression. A total of 2,442 participants were divided into two groups: no-surgery group (n = 1860) and surgery group (n = 582). Individuals in the no-surgery cohort showed a preference for radiation therapy (29.5

Background: Immune checkpoint blockade (ICB) has emerged as a promising therapy for both resectable urothelial carcinoma (UC) patients preparing for radical surgery and unresectable UC patients, whereas the objective response rate of ICB remains unsatisfactory due to various factors. Antibiotic (ATB) use can influence intratumoral bacteria, which may further reduce ICB efficacy. The study aims to evaluate the effects of ATB use on prognosis and response in UC patients undergoing ICB, and explore potential molecular mechanisms of ATBs and intratumoral bacteria impacting UC immune microenvironment. Materials and Methods: Pooled analyses, synthesizing evidence from 3496 UC patients with ICB treatment, were conducted. In addition, single-cell RNA and single-cell microbiome data were analyzed based on eight UC samples and 63 185 single cells. Bulk RNA sequencing and clinical data from a single-arm, multicenter, atezolizumab-treated, phase 2 trial, IMvigor210, were used for validation. Results: ATB use exhibited worse overall survival (HR=1.46, 95% CI=[1.20-1.77], P<0.001 and lower objective response (OR=0.43, 95% CI=[0.27-0.68], P<0.001 in UC patients receiving ICB. Single-cell transcriptome and single-cell microbiome analyses identified the presence of intratumoral bacteria was obviously related to elevated antibacterial immune functions; and antibacterial immunity was positively correlated to antitumor immunity in UC immune microenvironment. Intratumoral bacteria could up-regulate CD74-MIF/COPA signaling of immune cells and activation of CD74-MIF/COPA mediated the promotion of T cell antitumor function induced by antibacterial immune cells. UC patients with higher CD74-MIF/COPA signaling carried better overall survival (HR=1.60, 95% CI=[1.19-2.15], P=0.002) in immunotherapy cohort. Conclusion: ATB use reduces overall survival and objective response to ICB in UC patients. Antibacterial immune cell functions induced by intracellular bacteria in the UC microenvironment might up-regulate the function of antitumor T immune cells via activating CD74-MIF/COPA, whereas ATB could inhibit the above process through killing intracellular bacteria and result in poorer clinical benefit of ICB. The use of ATB should be considered carefully during the neoadjuvant immunotherapy period for resectable UC patients preparing for radical surgery and during the immunotherapy period for unresectable UC patients.

Background: Cisplatin-based combination chemotherapy alone is currently considered the standard of care for patients with metastatic upper tract urothelial carcinoma (mUTUC). However, less research has been done on the efficacy of other combinations. In this study, we explored the role of cytoreductive surgery in patients with mUTUC receiving different types of systemic therapy. Methods: Data from 9,436 anonymized records were abstracted from the Surveillance, Epidemiology, and End Results (SEER) database between 2008-2018. Of these, 508 individuals received systemic therapy subsequent to being diagnosed with mUTUC. These patients had all been treated with systemic therapies such as chemotherapy and/or radiotherapy. Patients were stratified into either a non-surgical or surgical group based on cytoreductive surgery status before systemic therapeutics commenced. Kaplan-Meier curves were used to compare overall survival (OS) and cancer-specific survival (CSS). Cox's proportional hazard models were then used to analyze prognostic factors related to OS and CSS. Results: Of the 508 cases, 36.8% (n=187) had received cytoreductive surgery with systemic treatments. The remaining 63.2% (n=321) received either chemotherapy and/or radiotherapy alone. Kaplan-Meier curves showed that 11.6% had 3-year OS [95% confidential interval (CI): 7.1-17.3] for cytoreductive surgery with systemic treatment and 4.9% (95% CI: 2.7-8.0) for systemic treatment alone (P=0.001). The 3-year CSS was 14.9% for cytoreductive surgery plus systemic treatment (95% CI: 9.4-21.7%) and 6.0% (95% CI: 3.4-9.8%) for systemic treatments alone (P=0.003). Under multivariate regression analysis, primary ureter site OS had a hazard ratio (HR) of 0.74 (95% CI: 0.58-0.95, P=0.02) and a CSS HR of 0.72 (95% CI: 0.56-0.94, P=0.01). The cytoreductive surgery OS HR was 0.79 (95% CI: 0.65-0.95, P=0.02) and the CSS HR was 0.75 (95% CI: 0.61-0.92, P=0.006). Additionally, chemotherapy had an OS HR of 0.46 (95% CI: 0.33-0.0.65, P<0.001) and a CSS HR of 0.44 (95% CI: 0.31-0.63, P<0.001). Bones and liver metastases were also indicative of poorer prognosis. Validation was conducted through subgroup analysis which suggested cytoreductive surgery was effective only for patients who received chemotherapy or combined chemo-radiotherapy but not for radiotherapy alone. Conclusions: Cytoreductive surgery provided significantly increased OS and CSS for mUTUC patients who received chemotherapy or combined chemo-radiotherapy in this study. In addition, the primary tumor and metastatic sites were shown to be related to improved patient survival although this was a small and relatively homogeneous cohort of study, sample therefore, further research is required.

Postoperative radiotherapy currently stands as the cornerstone of glioblastoma (GBM) treatment. Nevertheless, low-dose radiotherapy has been proven ineffective for GBM, due to hypoxia in the GBM microenvironment, which renders the resistance to radiation-induced cell death. Moreover, the overexpression of the PLK1 gene in glioma cells enhances GBM proliferation, invasion, metastasis, and resistance to radiation. This study introduced a hybrid membrane-camouflaged biomimetic lipid nanosensitizer (CNL@miPA), which efficiently encapsulated gold nanoclusters (PA) and miR-593-5p by a chimeric membrane derived from lipids, cancer cells, and natural killer cells. CNL@miPA exhibited exceptional blood-brain barrier and tumor tissue penetration, effectively ameliorating hypoxia and synergizing with radiotherapy. By enabling prolonged miRNA circulation in the bloodstream and achieving high enrichment at the tumor site, CNL@miPA significantly suppressed tumor growth in combination treatment, thereby significantly extending the survival period of treated mice. Overall, the developed biomimetic nanosensitizer represented an efficient and multifunctional targeted delivery system, offering a novel strategy for gene-radiotherapy of GBM.

The hypoxic nature of pancreatic cancer, one of the most lethal malignancies worldwide, significantly impedes the effectiveness of chemoradiotherapy. Although the development of oxygen carriers and hypoxic sensitizers has shown promise in overcoming tumor hypoxia. The heterogeneity of hypoxia—primarily caused by limited oxygen penetration—has posed challenges. In this study, we designed a hypoxia-responsive nano-sensitizer by co-loading tirapazamine (TPZ), KP372-1, and MK-2206 in a metronidazole-modified polymeric vesicle. This nano-sensitizer relies on efficient endogenous NAD(P)H quinone oxidoreductase 1-mediated redox cycling induced by KP372-1, continuously consuming periphery oxygen and achieving evenly distributed hypoxia. Consequently, the normalized tumor microenvironment facilitates the self-amplified release and activation of TPZ without requiring deep penetration. The activated TPZ and metronidazole further sensitize radiotherapy, significantly reducing the radiation dose needed for extensive cell damage. Additionally, the coloaded MK-2206 complements inhibition of therapeutic resistance caused by Akt activation, synergistically enhancing the hypoxic chemoradiotherapy. This successful hypoxia normalization strategy not only overcomes hypoxia resistance in pancreatic cancer but also provides a potential universal approach to sensitize hypoxic tumor chemoradiotherapy by reshaping the hypoxic distribution.

Despite extensive investigations, urosepsis remains a life-threatening and high-mortality illness. The absence of widely acknowledged animal models for urosepsis prompted this investigation with the objective of formulating a replicable murine model. Eighty-four adult male C57BL/6J mice were arbitrarily distributed into three cohorts based on the concentration of the Escherichia coli (E. coli) solution administered into the renal pelvis: Sham, Low-grade sepsis (1.0 × 108 cfu/mL), and High-grade sepsis (1.0 × 109 cfu/mL). By fabricating a glass needle with a 100 μm outer diameter, bacterial leakage during renal pelvic injection was minimized. After the ureteral ligation, the mice were injected with this needle into the right renal pelvis (normal saline or E. coli solution, 1 ml/kg). Ten days post after E. coli injection, the mortality rates for the Low-grade sepsis and High-grade sepsis groups stood at 30 % and 100 %, respectively. Post-successful modeling, mice in the urosepsis cohort exhibited a noteworthy reduction in activity, body temperature, and white blood cell count within a 2-h timeframe. At the 24-h mark post-modeling, mice afflicted with urosepsis displayed compromised coagulation functionality. Concurrently, multiple organ dysfunction was confirmed as evidenced by markedly elevated levels of inflammatory factors (IL-6 and TNF-α) in four distinct organs (heart, lung, liver, and kidney). This study confirmed the feasibility of establishing a standardized mouse model of urosepsis by ureteral ligation and E. coli injection into the renal pelvis. A primary drawback of this model resides in the mice's diminished blood volume, rendering continuous blood extraction at multiple intervals challenging.

OBJECTIVE:To assess prognostic differences between primary and progressive muscle-invasive bladder cancer (MIBC) following radical cystectomy. MATERIAL AND METHODS:The Surveillance, Epidemiology, and End Results (SEER) database was used to abstract MIBC data following radical cystectomy from 2000 to 2019. Patients were classified as either 'Primary' MIBC (defined as the presentation of muscle-invasive disease at initial diagnosis) or 'Progressive' MIBC (defined as a non-muscle invasive disease that later progressed to MIBC). Baseline characteristics for the two groups were balanced using a propensity score overlap weight (PSOW) technique. Survival differences between the two groups were analyzed using Kaplan-Meier's plots and log-rank tests. Cox's proportional hazard regression was used to assess risk factors associated with overall survival (OS) and cancer-specific survival (CSS). RESULTS:Six thousand six hundred thirty-two MIBC patients were identified in the SEER database. Among them, 83.3% ( n =5658) were considered primary MIBC patients, and 16.7% ( n =974) were categorized as progressive MIBC patients. Distribution of baseline covariates, including age, sex, race, T stage, N stage, tumour grade, marital status, and chemotherapy, were well-balanced after PSOWs were applied. After stable PSOW adjustments, Kaplan-Meier survival analysis showed that the CSS for progressive MIBC [hazard ratio (HR)=1.25, 95% confidence interval (CI): 1.12-1.38, P <0.001) was poorer than the primary MIBC group. However, the difference in OS (HR=1.08, 95% CI: 0.99-1.18) was not significant ( P =0.073). Multivariate analysis also suggested that patients with progressive MIBC have significantly poorer CSS (HR=1.24, 95% CI: 1.19-1.38, P <0.001) but not OS (HR=1.08, 95% CI: 0.99-1.18, P =0.089). CONCLUSION:CSS for progressive MIBC patients appears worse than for those with primary MIBC. This highlights the need to direct more resources for this patient population and particularly for high-risk cases of non-MIBC, where timely radical surgery will improve patients prognoses.