Cancer vaccines represent a promising approach within immunotherapies. These vaccines are tailored to target tumor-specific antigens, thereby offering a precision approach to cancer treatment. The key principles in developing therapeutic cancer vaccines include identifying appropriate vaccine targets and selecting effective vaccine delivery platforms. These delivery platforms are diverse and have evolved to enhance the immune response. This review explores live cancer vaccines and the biological entities involved. Live cancer vaccines leverage the use of various biological entities to stimulate an immune response. These biological entities including bacterial, yeast-based and viral vectors, have unique properties that can be harnessed to target and destroy cancer cells while eliciting a robust immune response. Clinical trials of cancer vaccines are investigating standalone and combination treatment strategies in the prophylactic, adjuvant, and palliative settings. This review offers insights into the current oncologic vaccine landscape and potential future development.

To evaluate the role of preoperative neutrophils to lymphocytes ratio (NLR) as a predictor for the response to BCG in patients with non-muscle invasive bladder cancer (NMIBC).

Nighty six patients with NMIBC were prospectively included in our study. Our study population was classified into two groups, based on pre-operative (NLR) either ⩽ or > 3. After receiving BCG, patients were followed up for 3 years to evaluate the correlation between BCG failure and (NLR).

Nighty two patients were evaluated at the end of our study. The NLR > 3 group of patients showed a higher age and T stage compared to the NLR ⩽ 3 group with a significant difference. BCG failure was reported to be higher in the NLR > 3 group with a failure rate of 66.7% compared to 28.3% in the other group (p-value < 0.001). Time to failure in NLR > 3 group compared to NLR ⩽ 3 group was 10.44 ± 4.3 and 15 ± 3.9 months respectively with a (p-value = 0.002). Univariate and multivariate logistic regression revealed that the most significant predictors of BCG failure were NLR > 3, Initial T stage, and age respectively.

BCG response is highly affected by the NLR, with a higher failure rate with NLR > 3.

Studies on the relationship of cigarette smoking with the risks of recurrence and progression of non-muscle-invasive bladder cancer (NMIBC) are inconsistent and prospective data are scarce. Therefore, we aimed to assess the association of smoking behavior with risks of NMIBC recurrence and progression. We used data of the prospective multi-center cohort study UroLife, including 1495 patients with NMIBC who reported information on smoking at 6 weeks post-diagnosis (baseline; reflecting present and pre-diagnosis). This included smoking status (also based on reporting 3 months post-diagnosis), intensity, duration, pack years, and time since smoking cessation, if applicable. Hazard ratios and 95% confidence intervals (CIs) for risks of first recurrence, multiple recurrences, and progression were computed using multivariable proportional hazards regression models. During a total median follow-up period of 4.6 years, 517 patients developed ≥1 recurrence and 163 had progression. Higher versus lowest categories of smoking intensities and pack years up to baseline were significantly associated with a higher risk of first recurrence. No significant linear associations were found, except for smoking intensity among BCG-treated patients (per 10 cigarettes/day increase: HR 1.23, 95%CI 1.02, 1.48). No associations for smoking status, duration, and time since cessation were observed. Analyses of multiple recurrence risk showed comparable results. Regarding progression risk, no consistent associations were found. In conclusion, heavier smoking was associated with higher recurrence risk, particularly among BCG-treated patients. This may be attributable to persistent damage through its carcinogenic compounds. Given the mixed results across different exposures, the effect of smoking behavior on NMIBC prognosis remains unclear.

MR urography (MRU) is an imaging technique that provides comprehensive evaluation of the kidneys, pelvicalyceal system, ureters, and urinary bladder. Although CT urography (CTU) remains the first-line imaging modality for the urinary tract, incremental improvements in MRU have allowed simultaneous imaging of the kidneys, collecting system, and urinary bladder with superior contrast resolution and tissue characterization, equivalent visualization of the upper tracts, and similar specificity for detection of noncalculous diseases of the collecting system compared with that of CTU. MRU has evolved into an alternative to CTU in the broader patient population and a first-line examination in specific patient populations for which CTU is less preferred. This subgroup includes pediatric patients, pregnant patients, patients needing recurring studies, and patients with poor renal function or severe allergies to iodinated contrast material. The most common techniques encompassing a conventional MRU examination include static-fluid T2-weighted imaging and gadolinium-enhanced urothelial and excretory phase imaging. The addition of dynamic contrast-enhanced MRI and diffusion-weighted imaging results in multiparametric MRU that increases diagnostic accuracy. Newer techniques, such as parallel imaging, compressed sensing, radial k-space sampling, and deep learning-based image reconstruction, can shorten examination times and improve image quality and patient compliance. Successful MRU interpretation relies on technique optimization, knowledge of various urinary tract pathologic conditions, and familiarity with different sequences, potential interpretive pitfalls, and artifacts. ©RSNA, 2025 Supplemental material is available for this article.

En bloc resection of bladder tumor (ERBT) has been introduced to enhance the quality of resection of bladder cancer. This review aims to compare the perioperative and oncological outcomes of ERBT and conventional transurethral resection of bladder tumor (cTURBT).

A literature search was conducted using the PubMed/Medline, Embase, and Web of Science databases to identify randomized controlled trials published until May 2024. The primary outcomes were the risk of recurrence and progression. The secondary outcomes were detrusor muscle (DM) presence, muscularis mucosae (MM) detectability, bladder perforation and obturator nerve reflex rates, operative time, length of catheterization and hospitalization, and residual tumor at repeat transurethral resection of bladder tumor (reTURBT).

Seventeen studies met our inclusion criteria. No statistically significant difference was observed in 12-mo recurrence (risk ratio [RR] 0.81, 95% confidence interval [CI]: 0.65-1.02; p = 0.08), 24-mo recurrence (RR 1.02, 95% CI: 0.85-1.22; p = 0.8), and 12-mo progression (RR 0.68, 95% CI: 0.05-10.14; p = 0.8) rates. ERBT was significantly associated with a higher DM presence (RR 1.10, 95% CI: 1.01-1.20; p = 0.02), while no statistically significant difference emerged in the residual tumor at reTURBT and MM detectability (all p > 0.05). ERBT was significantly associated with a lower risk of bladder perforation (p = 0.002) and obturator nerve reflex (p < 0.001). Finally, ERBT was significantly associated with longer operative time, lower catheterization time, and lower length of hospital stay. The main limitation was heterogeneity among the included studies.

ERBT is safer due to fewer intraoperative events, but there was no significant difference in oncological outcomes compared with cTURBT. Higher DM detection with ERBT enhances initial disease stratification, potentially improving clinical decision-making and care delivery.

En bloc resection of bladder tumors is associated with lower intraoperative complications than and superior histopathological information to the conventional resection technique. However, the absence of a difference in oncological outcomes underscores the influence of factors such as tumor characteristics, surgeon expertise, and postoperative care on subsequent events.

Bacillus Calmette-Guérin (BCG) reduces disease recurrence and progression in intermediate- and high-risk non-muscle-invasive bladder cancer (NMIBC). BCG-associated adverse events during instillations are common, leading to treatment cessation. Prophylactic use of quinolones in conjunction with BCG instillations is one approach for reducing BCG-associated adverse events. Our aim was to delineate the clinical impact of quinolone prophylaxis (QP) in patients receiving adjuvant BCG instillations for NMIBC.

In October 2024, a systematic search of MEDLINE, Embase, and the Cochrane Central Register of controlled trials was performed. Prospective and retrospective studies reporting comparative outcomes for patients with and without QP during BCG instillations were included. Outcomes were reported in a binary fashion. Random-effects meta-analysis using the weighted mean difference was conducted. Primary outcomes for pooled analyses included BCG-associated toxicities, the completion rate for BCG induction, the likelihood of antituberculosis treatment, and disease recurrence and progression at 12 mo.

The systematic review included five studies. Four randomised controlled trials were included in the meta-analysis, and one nonrandomised study was also included in the narrative review. The studies involved 445 patients, of whom 194 received QP + BCG and 251 received BCG alone. QP use was associated with lower incidence of class ≥2 (40.8% vs 54.7%; relative risk [RR] 0.79, 95% confidence interval [CI] 0.67-0.94; p = 0.006), and class ≥3 BCG-associated toxicities (25.3% vs 36.4%; RR 0.70, 95% CI 0.50-0.98; p = 0.04) and a higher completion rate for BCG induction (83.0% vs 70.6%; RR 1.16, 95% CI 1.01-1.34; p = 0.04). The 12-mo recurrence rates (14.7% vs 19.4%; RR 0.76, 95% CI 0.46-1.27; p = 0.3) and progression rates (4.5% vs 6.4%; RR 0.86, 95% CI 0.09-8.25; p = 0.9) did not significantly differ for QP + BCG versus BCG alone.

The use of QP with adjuvant BCG for NMIBC mitigated debilitating BCG-associated toxicities and improved the completion rate for BCG induction therapy.

Recent years have seen the use of photodynamic technologies concerning the detection and therapy of bladder cancer (BC) due to their rapid development and well-established therapeutic impact. However, a thorough analysis and bibliometric assessment of photodynamic technologies publishing trends in BC has not been completed yet.

Retrieving bibliographies from the Web of Science Core Collection limited the publication date to December 31, 2023, from January 1, 2004. We used VOSviewer (Version 1.6.19) and CiteSpace (Version 6.4 R1) for both statistical and visualization analysis.

We selected a total of 870 documents for analysis. The yearly publication findings show notable upward patterns over the last two decades. The Kochi Medical School in Japan was the most productive school, while the USA was the most productive nation. Japanese researcher Inoue Keiji published the highest number of photodynamic -related articles in BC. The most quoted and prolific journals were the Photodynamic Therapy and Photodiagnosis. According to the keyword analysis, the terms "cystoscopy," "carcinoma in situ," "drug delivery," "follow-up," "hexaminolevulinate," and "impact" are all relatively recent and hot field.

Our investigation produced a bibliometric outcome for the field, potentially opening up new research opportunities. We suggest that future research concentrate on in-situ carcinoma identification, photosensitizer invention, medication delivery enhancement, and photodynamic technology follow-up in BC.

Bladder cancer is one of the most common human malignancies worldwide. Aberrant activation of signal transducer and activator of transcription 3 (STAT3) is crucial to driving malignant progression and predicting poor prognosis of multiple human cancers, including bladder cancer, making STAT3 a promising target of cancer therapeutics. Cryptotanshinone (CTS) is an anticancer ingredient of Danshen ( Salvia miltiorrhiza ), a top-graded Chinese medicinal herb. However, whether CTS targets STAT3 to exert its cytotoxic effect on human bladder cancer remains unknown. Herein, we demonstrated that CTS is cytotoxic to multiple human urinary bladder transitional cell carcinoma (TCC) cell lines while sparing normal human urothelial cells. CTS provoked apoptosis-dependent bladder TCC cytotoxicity, as apoptosis blockage by z-VAD-fmk markedly rescued the clonogenicity of CTS-treated cells. Besides, CTS was found to suppress constitutive and interleukin 6-inducible activation of STAT3, evidenced by the downregulation of STAT3 tyrosine 705 phosphorylation and BCL2, a recognized STAT3 transcriptional target. Notably, ectopic expression of a dominant-active STAT3 mutant (STAT3-C) or BCL-2 alleviated CTS-induced apoptosis and clonogenicity inhibition, thus confirming STAT3 blockade as a pivotal mechanism of CTS's cytotoxic action on bladder TCC cells. Lastly, immunoblotting revealed that CTS lowered the levels of active JAK2, an upstream kinase that mediates STAT3 tyrosine 705 phosphorylation. Altogether, we conclude that the blockade of the JAK2/STAT3/BCL-2 antiapoptotic signaling axis is a vital mechanism whereby CTS provokes bladder cancer cytotoxicity. The current evidence implicates CTS's potential to be translated into a bladder cancer therapeutic agent.

Bladder cancer (BC) is one of the most common malignant tumors of the urinary system, and has a high recurrence rate and treatment resistance. Recent results indicate that mitochondrial metabolism influences the therapeutic outcomes of BC. Mitochondria-targeted photosensitizer (PS) is a promising anticancer therapeutic approach that may overcome the limitations of conventional BC treatments. Herein, two mitochondria-targeted iridium(III) PSs, Ir-Mito1 and Ir-Mito2, have been designed for BC treatment. Mechanically, Ir-Mito2 induced a decrease in mitochondrial membrane potential via white light activation, further triggering a reduction of the B-cell lymphoma 2 protein (Bcl-2)/Bcl-associated X protein (Bax) ratio and increment of cleaved caspase3. Meanwhile, the reduction of glutathione, deactivation of glutathione peroxidase 4 (GPX4), increase of acyl-CoA synthetase long chain family member 4 (ACSL4), and accumulation of lipid peroxide resulted in synergistically activating of ferroptosis and apoptosis. The results demonstrated that Ir-Mito2 exhibited excellent antitumor efficacy with superior biosafety in vivo. This work on light-activated and mitochondrial-targeted PS provides an innovative therapeutic platform for BC.

The prognostic biomarkers, or metabolites, have gained relevance due to their significance in predicting clinical and therapeutic outcomes and guiding informed therapy options. This systematic review and meta-analysis aimed to evaluate the prognostic significance of metabolites in non-muscle-invasive bladder cancer (NMIBC) through an array of literature. The PubMed, Web of Science, Embase, and Cochrane Library databases were comprehensively searched for eligible studies published between January 2010 and August 2022, using related keywords and MeSH terms. Two reviewers performed the extraction process, and a third reviewer settled possible controversies. The New Castle Ottawa scale (NOS) was used to determine the quality of selected studies. Pooled hazard ratios (H.R.s) with 95% confidence intervals (C.I.s) were calculated to establish the relationship of metabolites with NMIBC outcomes (recurrence-free survival (RFS), progression-free survival (PFS), and overall survival (O.S.) to establish their prognostic roles. A total of 15 studies, with a sample size of 5491, were included and analyzed in this study. Various metabolites were found to be correlated with the outcomes of the study: PFS (pooled HR, 4.48; 95% CI, 1.70-11.80, p = 0.002), RFS (pooled HR, 2.85; 95% CI, 1.91-4.26; p = 0.00001), and OS (HR, 1.78; 95% CI, 1.07-2.98; p = 0.03). Pretreatment metabolites or markers in NMIBC patients had a relationship with recurrence prediction and disease outcomes in bladder cancer. Therefore, metabolites may equally serve as a critical, independent prognostic predictor for NMIBC patients. This could be considered in most related clinical decisions in bladder cancer.

Patients with high-risk non-muscle-invasive bladder cancer (NMIBC) receive bacillus Calmette-Guérin (BCG) instillations to reduce the risk of progression. For patients with very high-risk NMIBC, immediate radical cystectomy may be considered, as patients who experience disease progression despite BCG treatment have a worse prognosis. However, guideline-recommended stratification for the risk of progression is based on data from patients who were not exposed to BCG. We evaluated the risk of progression in a contemporary cohort of patients with primary high-grade/grade 3 (HG/G3) T1 NMIBC (n = 1268) who received at least one BCG instillation and underwent at least one cystoscopic evaluation. The primary endpoint was the 1-yr risk of progression for all patients and for the subgroup that received adequate BCG, defined as at least five induction instillations and at least two instillations provided as a second BCG course within 6 mo. Progression was defined as detrusor muscle invasion or lymph node or distant metastasis. The 1-yr risk of progression was 6.5% (95% confidence interval [CI] 5.2-8.0) for patients with primary HG/G3 T1 NMIBC who started BCG treatment, and 4.6% (95% CI 3.3-6.4) 1 yr after the first instillation of the second BCG course for patients who received adequate BCG (n = 746). In conclusion, the contemporary risk of progression for patients with HG/G3 T1 NMIBC who receive BCG appears to be low, especially for patients who receive adequate BCG treatment. PATIENT SUMMARY: Our study shows that for patients with a high-grade bladder tumor who received in-bladder BCG (bacillus Calmette-Guérin), the risk of disease progression was 6.5% at 1 yr after their first BCG instillation. For patients who continued with BCG maintenance treatments, the risk of progression was 4.6% after the first BCG maintenance instillation.

Despite currently used intravesical therapies in non-muscle-invasive bladder cancer (NMIBC), the rate of intravesical recurrence remains very high. We aimed to evaluate the effectiveness of adding nonintravesical interventions to standard intravesical therapies to prevent intravesical recurrence. In April 2024, 3 databases were queried for prospective studies evaluating nonintravesical interventions in addition to standard intravesical therapies for NMIBC (CRD42024490988). The primary outcome was intravesical recurrence-free survival (iRFS). Standard pairwise meta-analyses were performed using hazard ratios (HR) and 95% confidence intervals (95% CI) with a random-effects model. We identified 18 eligible studies (14 RCTs and 4 prospective trials) comprising 4,593 NMIBC patients, which investigated pharmacological interventions (eg, selenium, vitamins, Lactobacillus casei, celecoxib, metformin, mistletoe lectin) and lifestyle modifications (diet). The addition of Lactobacillus casei significantly improved iRFS (HR: 0.50; 95% CI: 0.34-0.73; P < .001). A high western diet pattern significantly worsened iRFS (HR:1.48, 95%CI:1.06-2.06, P = .03). The other nonintravesical interventions were not associated with iRFS. Our comprehensive review of the published literature highlights the need for further research into the efficacy of nonvesical interventions for NMIBC. While Lactobacillus was shown to improve iRFS in 2 RCTs, additional high-quality randomized studies are required to evaluate the effectiveness of other interventions.

Bladder carcinoma (BC) is a common type of cancer. Approximately 20% of BC patients have non-muscle invasive bladder cancer (NMIBC). Despite adequate BCG treatment, recurrence occurs in approximately 40% of the patients. There is no adequate prognostic marker for recurrence in a group of patients. Forkhead box P3 (FOXP3) is a regulatory T cell marker that sometimes exhibits anti-tumoral effects and can be used as a tumor marker. T-cell immunoglobulin and mucin domain 3 (TIM-3) is an immune checkpoint inhibitor of T cells. Tertiary lymphoid structures (TLS) increase malignancy and inflammation in non-lymphoid organs. Therefore, we aimed to evaluate the prognostic value of FOXP3, TIM-3, and TLS in patients with NMIBC.

Patients with pathologically confirmed NMIBC were included in this study. Stromal and intraepithelial cells were evaluated separately using immunohistochemistry, and FOXP3, TIM-3, TLS, FOXP3/TLS, and TIM-3/TLS were calculated and noted. The cutoff value was determined using ROC analysis. Recurrence-free survival (RFS) and overall survival (OS) were evaluated using univariate and multivariate Cox proportional hazard analyses.

The study included ninety-six patients. FOXP3/TLS high group had a better RFS than FOXP3/TLS low group (P = 0.001; HR, 0.079; 95% CI, 0.019-0.337). This was also significant in the multivariate analysis (P = 0.018; HR, 0.125; 95% CI, 0.022-0.705). In the group receiving BCG, FOXP3/TLS, FOXP3-TLS, TIM-3-TLS and TIM-3/TLS elevation were lower in patients with relapse than in patients without relapse and were statistically significant. Combined TIM-3 and FOXP3 elevation was found to be good prognostic regardless of whether it was found in intraepithelial, stromal or TLS.

FOXP3/TLS elevation is a good prognostic and predictive marker in all non-muscle invasive bladder cancer cases and in the subgroup receiving BCG. Elevation of FOXP3-TLS, TIM-3-TLS, and TIM-3/TLS is associated with longer RFS in patients receiving BCG. Combined TIM-3 and FOXP3 elevation is indicative of a low recurrence rate in NMIBC.

Sequential intravesical gemcitabine/docetaxel (Gem/Doce) is a potential alternative to bacillus Calmette-Guérin (BCG) for treating non-muscle-invasive bladder cancer (NMIBC). Intermediate-risk NMIBC group (IR-NMIBC) includes both low-grade (LG) and high-grade tumors (HG). This study investigates the response of HG and LG IR-NMIBC to Gem/Doce compared to BCG therapy.

We included patients with IR-NMIBC who received either BCG or Gem/Doce between 2013 and 2023. Maintenance regimens were administered to patients without recurrence after induction for 1 year. Follow-up cystoscopies were performed per American Urological Association (AUA) guidelines. Kaplan-Meier and Cox regression analyses were performed to evaluate recurrence-free survival (RFS) and progression-free survival (PFS).

Among 505 NMIBC patients, 150 were IR-NMIBC: 115 with HG tumors (69 received BCG, 46 received Gem/Doce) and 35 with LG tumors (14 received BCG, 21 received Gem/Doce).With a median follow-up time of 31 months (Interquartile Range [IQR] 13-54), The overall 2-year any-grade RFS was 55%. For HG and LG groups, the 2-year any-grade RFS was 58% and 35% (P = 0.009), respectively. High-grade RFS at 2 years was 75% for HG and 94% for LG (P = 0.065). The 2-year PFS was similar between groups, at 96% for both HG and LG (P = 0.39). In HG patients, 2-year high-grade RFS was higher with BCG than Gem/Doce (81% vs. 59%, P = 0.008). In LG patients, 2-year any-grade and high-grade RFS were comparable between BCG and Gem/Doce (P = 0.067 and P = 0.37, respectively).

Our findings suggest that BCG may offer a superior benefit in terms of high-grade RFS for HG IR-NMIBC compared to Gem/Doce, while LG tumors respond similarly to both treatments. This emphasizes the role of risk stratification in treatment selection. Prospective studies are needed to validate these findings and refine treatment strategies.

Despite remarkable advancements in therapeutic strategies, a considerable proportion of patients with bladder cancer (BC) still experience disease progression and unfavorable prognosis. The heterogeneity and biological functions of tumor endothelial cells (ECs) during BC progression remain poorly understood. We collected scRNA-seq data from BC samples and identified two EC subpopulations through hierarchical clustering analysis. The activity of signaling pathways in distinct EC subpopulations was assessed utilizing AUCell analysis. Gene regulatory networks (GRN) were constructed and analyzed for different EC subpopulations using the pySCENIC algorithm. Additionally, we investigated the association between the abundance of EC subpopulations and both clinical prognosis and immune cell infiltration. The biological effects of ESM1 protein on BC cells were further validated through EdU and Transwell assays. We analyzed 7,519 CD45-negative single cells from BC tissues and discerned two distinct EC subpopulations. The two subpopulations were characterized by high expression of ESM1 (S1 ECs) and CXCL2 (S2 ECs), respectively. In S1 ECs, we observed significant activation of signaling pathways involved in tumor promotion, including angiogenesis and cell proliferation. Additionally, our GRN analysis uncovered notable differences in transcription factor activity between S1 and S2 ECs. Moreover, ESM1 protein promoted proliferation and migration of BC cells. Patients with higher abundance of the S1 EC subpopulation exhibited more unfavorable clinical outcomes and increased infiltration of inhibitory immune cells. Our findings elucidate the transcriptional profiles and biological roles of the high ESM1-expression endothelial cell subpopulation in BC. This subpopulation is associated with poor prognosis and immunosuppressive tumor microenvironment. Accordingly, targeting endothelial cells with high ESM1 expression may offer a novel therapeutic strategy for patients with BC.

To comprehensively evaluate the efficacy of different energy sources used for en-bloc transurethral resection of bladder tumors (ERBT) on perioperative outcomes.

This sub-analysis derived from a prospective randomized study that enrolled patients undergoing ERBT vs conventional transurethral resection of the bladder (cTURB) from January 2019 to January 2022 (NCT03718754). Endpoints were pathological specimen quality and perioperative outcomes after either monopolar (m-ERBT) or bipolar (b-ERBT) or laser (l-ERBT) ERBT.

237 bladder tumors resected in 188 patients included in the analyses: 29 (12.2%) m-ERBT, 136 (57.4%) b-ERBT and 72 (30.4%) l-ERBT. Detrusor muscle (DM) was detected in 191 (80.6%) specimens. Per-tumor analysis revealed comparable rate of DM in the specimens obtained via different energy modalities (p = 0.7). Operative time was longer in the l-ERBT cohort compared to m-ERBT and b-ERBT (p = 0.02) and no obturator nerve reflex (ONR) onset was reported. On logistic regression analysis, b-ERBT was associated with negative lateral resection margins (OR 2.81; 95% CI 1.02-7.70; p = 0.04). There was no significant association of the resection technique with perforation and conversion rates (all p > 0.05). Within a median follow up of 22mo (IQR 11-29), a total of 35 (18.6%) patients had a local recurrence. On Cox regression analysis, patients resected with b-ERBT were less likely to have a recurrence (HR 0.34; 95% CI 0.15-0.78; p = 0.01); When adjusting for established confounders, this association was confirmed (HR 0.24; 95% CI 0.10-0.60; p = 0.002).

Different energy sources might achieve comparable perioperative outcomes. Further perspectives involve the assessment of long-term differential oncological outcomes associated with various energy modalities.

To identify risk factors for prostatic urethral involvement (PUI) in bladder cancer and develop an accurate nomogram prediction model. We retrospectively analyzed 295 male patients with bladder urothelial carcinoma undergoing transurethral prostatic biopsy. Risk factors of PUI in bladder cancer were assessed through univariate and multivariate logistic regression analyses. A nomogram model for predicting clinical outcomes was constructed based on the independent risk factors of PUI. The performance of the model was internally validated by 'leave-one-out' cross-validation (LOOCV) and calibration curve. The decision curve analysis (DCA) was applied to evaluate the clinical utility. Further evaluation of PUI and associated risk factors within the context of non-muscle-invasive bladder cancer (NMIBC) were assessed using the same methods. Multivariate analysis revealed that the tumor multiplicity (OR = 2.44, 95% CI 1.17-5.26, P = 0.019), trigonal/neck tumor location (OR = 7.42, 95% CI 4.00-14.24, P < 0.001), high-grade tumor (OR = 5.17, 95% CI 1.52-21.95, P = 0.014), and recurrent carcinoma (OR = 4.39, 95% CI 2.32-8.63, P < 0.001) were identified as independent risk factors for PUI in bladder cancer (all P < 0.05). A final prediction nomogram was established based on these four independent risk factors. After internally validated by LOOCV, the nomogram showed strong discrimination (area under the curve, AUC = 0.8, 95%CI 0.749-0.851) and excellent calibration. DCA further confirmed the model's clinical utility across a wide range of risk thresholds. Subgroup analysis in NMIBC yielded consistent results (AUC = 0.819, 95%CI 0.764-0.874). This nomogram provides a robust tool to stratify PUI risk in bladder cancer, guiding selective prostatic biopsies and personalized management. Integration into clinical workflows may reduce understaging and optimize outcomes. Further external validation is warranted.

Objectives: There are no unanimous recommendations between urology societies regarding the performance of a urine culture before Bacillus Calmette-Guérin (BCG) instillations. The management of a positive urine culture before each instillation depends on the choice of the urologist. The objective of our study was to collect urine cultures performed before instillations and to study their impact on the risk of associated urinary tract infection (UTI) and on the risk of recurrence of bladder tumors. Patients and Methods: A retrospective analysis of induction BCG files (six instillations per cycle) associated or not with maintenance BCG (three instillations per cycle) was performed between January 2022 and January 2023. A urine culture was systematically carried out a few days before each instillation. In the event of a positive urine culture, the choice of treatment depended on the referring urologist. Demographic data, tumor characteristics, risk factors for UTI, and bacteriological data (date of urine culture, leukocyturia, hematuria, polymicrobial, sterile, and antibiotic therapy given) were collected. Results: Eighty patients were included, all with non-muscle-infiltrating bladder tumors. A total of 812 urine cultures were studied, of which 88 were positive. Among all positive urine cultures, 42 did not receive antibiotics, and yet no febrile UTI was detected. A serious infectious event was reported in two patients including one death, and no risk factor for the occurrence of a positive urine culture could be identified. Bladder tumor recurrence was identified in 17 patients, 3 of whom had positive urine culture treated with antibiotics. Conclusions: Performing urine culture before BCG instillation does not seem necessary. Antibiotic therapy for a positive urine culture could expose to a higher risk of recurrence.

Accurately assessing the prognosis of bladder cancer patients after radical cystectomy has important clinical and research implications. Current models, based on traditional statistical approaches and complex variables, have limited performance. We aimed to develop a machine learning (ML)-based prognostic model to predict 5-year cancer-specific mortality (CSM) in bladder cancer patients undergoing radical cystectomy, and compare its performance with current validated models.

Patients were selected from the Surveillance, Epidemiology, and End Results database and the First Affiliated Hospital of Sun Yat-sen University for model construction and validation. We used univariate and multivariate Cox regression to select variables with independent prognostic significance for inclusion in the model's construction. Six ML algorithms and Cox proportional hazards regression were used to construct prediction models. Concordance index (C-index) and Brier scores were used to compare the discrimination and calibration of these models. The Shapley additive explanation method was used to explain the best-performing model. Finally, we compared this model with three existing prognostic models in urothelial carcinoma patients using C-index, area under the receiver operating characteristic curve (AUC), Brier scores, calibration curves, and decision curve analysis (DCA).

This study included 8,380 patients, with 6,656 in the training set, 1,664 in the internal validation set, and 60 in the external validation set. Eight features were ultimately identified to build models. The Light Gradient Boosting Machine (LightGBM) model showed the best performance in predicting 5-year CSM in bladder cancer patients undergoing radical cystectomy (internal validation: C-index = 0.723, Brier score = 0.191; external validation: C-index = 0.791, Brier score = 0.134). The lymph node density and tumor stage have the most significant impact on the prediction. In comparison with current validated models, our model also demonstrated the best discrimination and calibration (internal validation: C-index = 0.718, AUC = 0.779, Brier score = 0.191; external validation: C-index = 0.789, AUC = 0.884, Brier score = 0.137). Finally, calibration curves and DCA exhibited better predictive performance as well.

We successfully developed an explainable ML model for predicting 5-year CSM after radical cystectomy in bladder cancer patients, and it demonstrated better performance compared to existing models.

Intravesical instillation of bacillus Calmette-Guérin (BCG) is the standard treatment for bladder carcinoma in situ (CIS); however, factors that predict its therapeutic efficacy have not been identified. We focused on immune cells infiltrating within 20 μm of tumor cells and examined factors that predict the efficacy of intravesical BCG treatment.

Formalin-fixed, paraffin-embedded tissue specimens from 82 patients with bladder CIS treated with intravesical BCG were used. Patients who relapsed after BCG treatment were grouped as non-responders, and those who did not were grouped as responders. Tissue sections were immunostained for CD4, CD8, and forkhead box P3 (FOXP3), a marker of regulatory T cells (Tregs). The number of immune cells positive for the above markers present within 20 μm of the lower edge of the basement membrane on which CIS is present was counted and compared between groups.

Both the peritumoral Treg density and Treg+/CD4+ cell ratio were significantly greater in nonresponders than in responders. The patients were divided into high and low groups based on Treg density and Treg+/CD4+ cell ratio cut-off values; recurrence-free survival was significantly longer in the low group than in the high group (p = 0.005 and p < 0.001, respectively).

The Treg density and Treg+/CD4+ cell ratio within 20 μm of bladder CIS may be useful predictors of therapeutic response to BCG.

SUMMARYFor several decades, intravesical Bacillus Calmette-Guérin (iBCG) immunotherapy has been the gold standard adjuvant treatment for high-risk and selected intermediate-risk patients with non-muscle-invasive bladder cancer (NMIBC). In this review, the mechanisms of iBCG immune-mediated anti-cancer activity and resistance are presented. Furthermore, a literature review of short-term and systemic iBCG-related side effects was performed. A high incidence (75.5%) of iBCG-related short-term, self-limiting adverse events was observed, while more severe iBCG-related local/systemic complications (iBCG-rL/SCs) that required medical treatment or hospitalization occurred at a lower rate (2.35%). Disseminated was the most common form of iBCG-rSCs, while two-thirds of the cases were classified as infectious. The implementation of molecular-based techniques resulted in significantly higher diagnostic rates. Anti-tuberculous treatment (ATT) is the mainstay of treatment, while in patients with any iBCG-rL/SC form involving the vasculature, ATT should be combined with surgery. Local and osteoarticular forms have the lowest mortality, but their management necessitates severe and debilitating surgical procedures. The overall iBCG-attributed mortality in patients with iBCG-rL/SC was 7.4%, with disseminated, vascular, and lung involvements exhibiting the highest rates. Given the global shortage of BCG for the last two decades, as well as the paucity of effective options for iBCG-refractory or relapsing NMIBC patients, new therapeutic strategies are being tested with promising early results.

We evaluated the prognostic significance of the Lactate Dehydrogenase-to-Serum Albumin Ratio (LAR), Fibrinogen-to-Albumin Ratio (FAR), and Platelet-to-Lymphocyte Ratio (PLR) in patients with high-grade urothelial carcinoma (HGUC) of the bladder who underwent radical cystectomy (RC). These markers have been reported to be associated with the prognosis of various cancers.

A retrospective analysis was conducted on HGUC patients who underwent RC at Guangxi Medical University Cancer Hospital between January 2013 and June 2021. Optimal cutoff values for LAR, FAR, and PLR were established. Kaplan-Meier survival analysis was used to evaluate survival outcomes, while univariate and multivariable Cox regression analyses identified independent prognostic factors. A nomogram was developed to predict survival, with validation through time-dependent receiver operating characteristic (ROC) curves, calibration plots, and decision curve analysis (DCA).

A total of 180 patients were included, with a follow-up period ranging from 2 to 127 months (49.28 ± 37.87 months). The optimal cutoff values for LAR, PLR, and FAR were 4.46, 139.68, and 0.13, respectively. Multivariable Cox regression identified tumor stage, LAR, PLR, and FAR as independent prognostic factors. Specifically, Stage III (HR = 25.44, 95% CI: 5.20-124.35, p < 0.001) and Stage IV (HR = 11.28, 95% CI: 3.18-40.05, p < 0.001) were independent risk factors for poor survival. A low PLR (HR = 0.45, 95% CI: 0.27-0.76, p = 0.003), low FAR (HR = 0.51, 95% CI: 0.29-0.89, p = 0.018), and low LAR (HR = 0.39, 95% CI: 0.23-0.67, p < 0.001) were independently associated with improved survival. The nomogram demonstrated high accuracy in predicting 1-, 3-, and 5-year overall survival (OS), with area under the curve (AUC) values of 0.866, 0.84, and 0.831, respectively. Further validation confirmed the model's stability and clinical applicability.

LAR, PLR, and FAR are promising prognostic factors for HGUC of the bladder following RC, showing substantial potential for prognostic evaluation.

This research aimed to identify the most effective energy source for en bloc resection of non-muscle-invasive bladder cancer (NMIBC) by a systematic review and network meta-analysis of randomized controlled trials (RCTs) and observational studies. We assessed and contrasted the effectiveness and safety of various energy modalities used in en bloc resection (ERBT) with those employed in conventional transurethral resection of bladder tumor (cTURBT).

A thorough search was conducted in PubMed, EMBASE, Cochrane, and Web of Science (WOS) to discover relevant articles published till August 29, 2024. Research comparing en bloc resection using various energy sources (such as hybrid knife, holmium laser, thulium laser, green-light laser, monopolar, and bipolar devices) to conventional transurethral resection of bladder tumor (cTURBT) was included. A network meta-analysis was performed using Stata/MP 18.0. Standardized mean differences (SMD) were computed for continuous outcomes, whilst relative risks (RR) were used for dichotomous outcomes. Nine clinical outcomes were assessed: duration of surgery, length of hospital stay, catheterization duration, irrigation duration, volume of intraoperative blood transfusion, 12-month recurrence rate, bladder perforation rate, incidence of obturator nerve reflex, and presence of detrusor muscle in the resected specimen. (PROSPERO ID: CRD42024623881).

The study included 37 research, including 8 randomized controlled trials (RCTs) and 29 high-quality non-randomized controlled trials (NRCTs), with a total of 4973 patients involved. The network meta-analysis revealed that ERBT was much better than cTURBT in the majority of outcomes. Hybrid knife and laser technologies (holmium, thulium, and green-light lasers) shown superior efficacy regarding decreased surgical length, diminished 12-month recurrence rates, and fewer problems. Hybridknife proved to be the most advantageous energy source for various results, while cTURBT consistently exhibited the least effective performance across all metrics.

En bloc resection surpasses traditional TURBT in the management of NMIBC, with various energy modalities exhibiting distinct benefits. Among the assessed energy sources, laser technologies and hybrid knives regularly surpassed monopolar and bipolar devices. These findings provide critical direction for urologists in selecting the most suitable energy source for en bloc resection in NMIBC, emphasizing the need for individualized decision-making based on the patient's distinct variables and tumor attributes.

RNA-binding proteins (RBPs) are pivotal mediators of the alternative splicing (AS) machinery of pre-mRNA. Research has demonstrated that the AS process is significantly dysregulated and plays a crucial role in bladder cancer (BLCA). We conducted comprehensive screening and analysis of the TCGA-BLCA cohort, specifically focusing on genes with significant differences in expression levels between carcinoma and adjacent non-cancerous tissues. Among the 500 differentially expressed genes, 5 RNA-binding proteins were identified. Only the RNA-binding protein with multiple splicing (RBPMS) demonstrated a consistent downregulation in BLCA and was correlated with an unfavorable prognosis for affected patients. Subsequent experiments revealed that RBPMS exerted inhibitory effects on the epithelial-mesenchymal transition (EMT) pathway and the migratory potential of BLCA cells. RNA-Seq analysis identified ANKRD10 as a key target mRNA regulated by RBPMS in BLCA. RBPMS depletion in BLCA cells resulted in AS of ANKRD10 and increased ANKRD10-2 expression. ANKRD10-2 functioned as a transcriptional co-activator of MYC proteins, thereby augmenting their transcriptional activity. Furthermore, ANKRD10-2 knockdown significantly rescued the migration enhancement induced by RBPMS depletion in BLCA cells. Taken together, this study revealed a mechanism whereby RBPMS suppresses the migration and invasion of BLCA cells by attenuating MYC pathway activity via the AS of ANKRD10.

Combinations of immune checkpoint inhibitors and nab-paclitaxel have improved outcomes in advanced urothelial carcinoma and muscle-invasive bladder cancer. This study evaluates the safety and efficacy of tislelizumab combined with low-dose nab-paclitaxel in extensive very high-risk non-muscle-invasive bladder cancer.

TRUCE-02 was a single-arm phase II trial that included 63 patients with visually incomplete resection and/or high-volume high-grade T1 tumors (with or without carcinoma in situ) who were ineligible for or declined radical cystectomy. Patients received intravenous tislelizumab (200 mg on day 1) and nab-paclitaxel (200 mg on day 2) every 3 weeks, with assessment approximately 3 months after initial administration. The primary endpoint was the complete response (CR) rate of high-risk disease. Main secondary endpoints included safety and duration of CR.

The safety analysis included all 63 patients, and the efficacy analysis included 59 patients. Thirty-seven patients (62.7%; 95% confidence interval, 49.1%-75.0%) achieved a CR of high-risk disease, with a 24-month sustained response rate of 96.3% (95% confidence interval, 89.4%-100.0%). Grade 3 to 4 treatment-related adverse events occurred in nine patients (14%), with no fatal events reported.

Tislelizumab plus low-dose nab-paclitaxel was well tolerated and showed promising antitumor activity, making it a potential alternative for patients with extensive very high-risk non-muscle-invasive bladder cancer who are ineligible for or decline radical cystectomy.

To investigate whether the timing of bacillus Calmette-Guerin instillation (TTBCG), which plays a key role in treating non-muscle invasive bladder cancer (NMIBC), after transurethral resection of bladder tumor (TURBT) affects oncologic outcomes.

Patient data obtained from the Urologic Cancer Database-Bladder (UroCaD-B) of Turkish Uro-oncology Association (TUOA) were evaluated. Data from 292 patients from 12 centers with primary T1HG treated with TURBT and maintenance BCG between 2003 and 2023 were retrospectively analyzed. The population was subdivided according to TTBCG, while recurrence-free survival (RFS) and progression-free survival (PFS) were estimated by log-rank tests and univariable and multivariable regression analyses.

A total of 292 patients were followed, and 86% (n=251) of those included in the study were male. The median duration of TTBCG was 38.5 days (19-73). The median follow-up period was 38.4 months (21.5-72.1 months). During follow-up, recurrence was detected in 55 (18.5%) patients and progression was detected in 22 (7.5%) patients. In univariate Cox regression analysis, long TTBCG (>27.5 days) was found to have a statistically significant effect on the risk of short RFS and PFS (P=.05). BCG-related side effects were not associated with TTBCG (P=.313). Kaplan-Meier analysis showed that there was a significant difference in RFS and PFS between the TTBCG groups (P=.04, P=.011, respectively).

In this retrospective non-randomized study, we showed the negative effects of BCG delay on progression and recurrence in T1HG patients. Therefore, we think that BCG should be instilled within 4 weeks after surgery.

The nonmuscle invasive bladder cancer treated with BCG instillations in patients who smoke could potentially lead to poorer oncological results in the light of the new EAU risk groups classification for NMIBC that did not include BCG treated patients or smoking status.

Outcomes from 1313 patients with nonmuscle invasive bladder cancer treated with TURBT, re-TURBT and BCG instillations at 13 academic hospital centers, since 2002, has been included in this retrospective study. The study variables, including cumulative smoking exposure have been analyzed. A multivariable Cox proportional hazard model was used to assess associations between smoking variables and disease progression and repeated in the EAU high risk and very high-risk group. The statistical significance threshold was set at 0.05, and the statistical analysis was performed using Stata/SE version 17 (StataCorp, College Station, TX, USA).

Cox regression analysis revealed in 1313 patients diagnosed with T1G3 NMIBC that patients with a history of heavy and long-term smoking faced a more than twofold increased risk of disease progression compared to nonsmoker patients (HR 2.35; 95% CI: 1.7-3.2; P < 0.01) and a significantly poorer PFS for patients with a history of heavy long-term smoke exposure (P < 0.01). Patients with heavy long-term smoking exposure according to the EAU21 high-risk group had a PFS comparable to very high-risk patients and high-risk patients with heavy long-term smoking exposure showed a higher risk of progression when compared to the high-risk group (HR 1.4; 95% CI: 1.3-1.6; P < 0.01).

This study adds valuable information on the relationship between smoking and the progression of NMIBC and BCG therapy. The findings emphasize the need for healthcare providers to consider a patient's smoking history when managing NMIBC and express the need for individualized smoking cessation counseling and individualized treatment approach.

Bladder cancer's high mortality underscores the need for precise staging, especially to differentiate between nonmuscle invasive bladder cancer (NMIBC) and muscle invasive bladder cancer (MIBC) types. This prospective study evaluated the efficacy of contrast-enhanced ultrasound (CEUS) for preoperative staging, focusing on its ability to distinguish NMIBC from MIBC. Conducted from April 2020 to September 2021, the study involved 163 patients (median age: 64.0 years; 137 males, 26 females), with 133 NMIBC (81.6%) and 30 MIBC (18.4%). Each patient underwent CEUS followed by transurethral resection of bladder tumor or radical cystectomy. CEUS demonstrated high diagnostic accuracy in determining muscle invasion status (sensitivity 83.3%, specificity 92.5%, accuracy 90.8%, area under the receiver operating characteristic curve [AUC] 0.88). Comparative analyses against MRI (AUC 0.77) showed CEUS outperforming in muscle invasion detection. Combining CEUS with MRI improved diagnostic accuracy, particularly when MRI vesical imaging reporting and data system score was 3 points. The combined approach achieved an AUC of 0.73, with sensitivity, specificity, and accuracy of 76.2, 70.2, and 71.6%, respectively. Thus, CEUS emerges as a valuable diagnostic tool for preoperative staging of bladder cancer, particularly in its role in assessing muscle invasion status and thereby aiding in clinical decision-making and intervention outcomes.

Accurately assessing 5-year recurrence rates is crucial for managing non-muscle-invasive bladder carcinoma (NMIBC). However, the European Organization for Research and Treatment of Cancer (EORTC) model exhibits poor performance.

To investigate whether integrating multiparametric MRI (mp-MRI) with clinical factors improves NMIBC 5-year recurrence risk assessment.

Retrospective.

One hundred ninety-one patients (median age, 65 years; age range, 54-73 years; 27 females) underwent mp-MRI between 2011 and 2017, and received ≥5-year follow-ups. They were divided into a training cohort (N = 115) and validation/testing cohorts (N = 38 in each). Recurrence rates were 23.5% (27/115) in the training cohort and 23.7% (9/38) in both validation and testing cohorts.

3-T, fast spin echo T2-weighted imaging (T2WI), single-shot echo planar diffusion-weighted imaging (DWI), and volumetric spoiled gradient echo dynamic contrast-enhanced (DCE) sequences.

Radiomics and deep learning (DL) features were extracted from the combined region of interest (cROI) including intratumoral and peritumoral areas on mp-MRI. Four models were developed, including clinical, cROI-based radiomics, DL, and clinical-radiomics-DL (CRDL) models.

Student's t-tests, DeLong's tests with Bonferroni correction, receiver operating characteristics with the area under the curves (AUCs), Cox proportional hazard analyses, Kaplan-Meier plots, SHapley Additive ExPlanations (SHAP) values, and Akaike information criterion for clinical usefulness. A P-value <0.05 was considered statistically significant.

The cROI-based CRDL model showed superior performance (AUC 0.909; 95% CI: 0.792-0.985) compared to other models in the testing cohort for assessing 5-year recurrence in NMIBC. It achieved the highest Harrell's concordance index (0.804; 95% CI: 0.749-0.859) for estimating recurrence-free survival. SHAP analysis further highlighted the substantial role (22%) of the radiomics features in NMIBC recurrence assessment.

Integrating cROI-based radiomics and DL features from preoperative mp-MRI with clinical factors could improve 5-year recurrence risk assessment in NMIBC.

3 TECHNICAL EFFICACY: Stage 3.

Depending on the risk status, the treatment options for non-muscle-invasive bladder cancer (NMIBC) can include a bladder-preserving strategy with intravesical instillation treatment or early radical cystectomy. Established intravesical treatment options such as mitomycin C (MMC) or Bacillus Calmette-Guérin (BCG) are available to reduce the probability of progression and recurrence. This article classifies the intravesical treatment options in the therapeutic landscape of NMIBC and provides an overview of the indications and application regimens.

The efficacy of Vesical Imaging-Reporting and Data System (VI-RADS) for the second transurethral resection (TUR) has not been adequately validated. This study aimed to evaluate the utility of the VI-RADS for high-risk patients with non-muscle-invasive bladder cancer (NMIBC) who are candidates for a second TUR.