Non-muscular Invasive Bladder Cancer Research Articles

A novel signature constructed by differential genes of muscle-invasive and non-muscle-invasive bladder cancer for the prediction of prognosis in bladder cancer.

Bladder cancer (BCa) is a malignant tumor that usually forms cancer cells in the inner lining of the bladder. Hundreds of thousands of people worldwide have BCa diagnosed each year. The purpose of this study was to construct a prognostic model by differential expression of genes between muscular and non-muscular invasive BCa, and to investigate the prognosis of BCa patients. The data of BCa patients was sourced from the GEO and TCGA database. Single-cell sequencing data was obtained from three patients in the GSE135337 database, and microarray data for verification was obtained from GSE32894. Univariate, Lasso and multivariate cox regression analyses were performed to construct the prognostic model. The prognostic features, immune features and drug sensitivity of the model were further evaluated. Single-cell data and microarray data were used to validate the differential expression of model genes between muscle-invasive and non-muscle-invasive BCa. The invasion and migration of BCa cells were evaluated using the transwell assay and wound-healing assay. The cell proliferation capacity was simultaneously evaluated using Colony formation experiments. The protein expression of the specific gene was detected by western blot analysis. We identified 183 differentially expressed muscle-invasive-related differential genes (MIRDGs), among which four were selected to establish a prognostic model. Based on our signature, patients in different groups displayed varying levels of immune infiltration and immunotherapy profiles. Single-cell sequencing data and microarray data confirmed that four invasion-related genes were expressed at higher levels in muscle-invasive BCa. Given the critical role of S100A9 in the progression of BCa, we performed further analysis. The results showed that protein expression of S100A9 was high in muscle-invasive BCa, and S100A9 knockdown could inhibit the proliferation, migration and invasion of BCa. These findings demonstrated that the prognostic model for BCa patients was reasonably accurate and valid, and it may prove to be of considerable value for the treatment and prognosis of BCa patients in the future. S100A9 may become a better prognostic marker and potential therapeutic target to further guide clinical treatment decisions.

3-year experience of hyperthermic intravesical chemotherapy use in patients with high risk non-muscular-invasive bladder cancer

Cur rently, the search for additional organ-sparing methods of intravesical therapy for non-muscular-invasive bladder cancer (NMIBC) is actively continuing, which could become an effective alternative to standard treatment using the Bacillus Calmette-Guérin (BCG) vaccine. The aim of this work was to analyze the safety profile and long-term results of treatment of patients with the high-risk non-muscular-invasive bladder cancer who received adjuvant intravesical chemotherapy using the Combat BRS HIVEC® device for local hyperthermia (HIVEC® therapy group; n=53) in comparison with patients who received adjuvant therapy after transurethral resection of bladder performed with the Bacillus Calmette-Guérin vaccine (BCG therapy group; n=54). As a result, the median follow-up was 30 months (range 7-36). According to Common Terminology Criteria for Adverse Events (CTCAE) v 5.0, the most relevant side effects in HIVEC®/BCG therapy groups were adverse events grade 1-2: fever – 1%/8%; dysuria – 9%/13%; bladder spasms – 7%/12%; hematuria – 3%/4% and urinary tract infection – 3%/10%. Tumor recurrence was reported in 23 patients receiving intravesical BCG therapy and in 10 patients receiving intravesical hyperthermic chemotherapy (42.6% versus 18.9%, p=0.008). Tumor progression was recorded in 11 patients receiving intravesical BCG therapy and in 4 patients receiving intravesical hyperthermic chemotherapy (20.4% versus 7.5%, p=0.046). The study allows us to conclude that the method of hyperthermic intravesical chemotherapy has a better safety profile compared to intravesical Bacillus Calmette–Guérin vaccine therapy, while such indicators of oncological efficacy as 3-year recurrence-free survival and the incidence of progression were better in the HIVEC® therapy group.

Multiple directional DWI combined with T2WI in predicting muscle layer and Ki-67 correlation in bladder cancer in 3.0-T MRI.

To investigate the value of 3.0T MRI multi-directional diffusion-weighted imaging (DWI) combined with T2WI morphological features and lesion distribution in preoperative prediction of muscle layer invasion of bladder cancer (BC) and the correlation with postoperative Ki-67. This retrospective study enrolled patients with BC between 2019 and 2021. Patients with muscular invasive bladder cancer (MIBC) or non-muscular invasive BC (NMIBC) were also analyzed by preoperative 3.0T MRI aFostic efficacy. A total of 186 patients were enrolled. About 27 patients with MIBC (35 lesions in total) and 62 with NMIBC (99 lesions in total). We found the tumor with a larger size, a wide base, and a smaller apparent dispersion coefficient (ADC) value and normalized ADC(nADC) value, without a stalk, presenting a greater risk of muscle invasion. ADC value, nADC value, maximum diameter, and stalk were independently associated with muscle invasion. Lesions located at the bladder fundus or involvement of multiple sites were independently associated with muscle invasion compared to the bladder body. In combination with morphological features, the AUCs of ADC and nADC showed accuracies of 0.925 and 0.947-0.951, respectively. TADC and nTADC showed the best diagnostic efficacy in multiple respects. KI-67 LI was negatively correlated with ADC and nADC values. This is the first report in which we found Multi-directional DWI combined with T2WI in 3.0T MRI can be used to predict the muscle layer invasion of bladder cancer. ADC values reflect the muscular invasion of bladder cancer and show a moderate negative correlation with Ki-67. It is especially suitable for bladder cancer patients with renal insufficiency or tumor recurrence.

CCNB2 as a potential biomarker of bladder cancer via the high throughput technology.

Bladder cancer and oral squamous cell carcinoma (OSCC) seriously affect people's health. However, the relationship between bladder cancer and OSCC remains unclear. Got GSE138206, GSE146483, GSE184616, and bladder cancer datasets GSE65635, GSE100926 from Gene Expression Omnibus database. Weighted gene co-expression network analysis was used to identify the significant module. Functional enrichment analysis was performed via the Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes. Furthermore, the Gene Set Enrichment Analysis was also used to complete the enrichment analysis. Comparative Toxicogenomics Database found most relevant diseases to core genes. TargetScan is used to forecast analysis of microRNA and target genes. In Gene Ontology analysis, differentially expressed genes were mostly concentrated in cell differentiation, extrallular region, structural molecule activity, and actin binding. In Kyoto Encyclopedia of Genes and Genomes analysis, the differentially expressed genes were mainly enriched in PI3K-Akt signaling pathway, pathway in cancer, and extracellular matrix-receptor interaction. Seven hub genes (cyclin B2 [CCNB2], TK1, CDC20, PCNA, CKS1B, CDCA5, MCM4) were obtained. Hub genes (CCNB2, CDC20) are highly expressed in OSCC and bladder cancer samples. CCNB2 was one common oncogene of bladder cancer and OSCC.

A prospective randomized study comparing short-time with long-time continuous saline bladder irrigation after transurethral resection in non-muscular invasive bladder cancer

A prospective randomized study comparing short-time with long-time continuous saline bladder irrigation after transurethral resection in non-muscular invasive bladder cancer

The different predictive value of mean platelet volume-to-lymphocyte ratio for postoperative recurrence between non-muscular invasive bladder cancer patients treated with intravesical chemotherapy and intravesical chemohyperthermia.

The inflammatory response plays a potential role in postoperative recurrence in patients with non-muscular invasive bladder cancer (NMIBC). We aimed to investigate whether platelet-to-lymphocyte ratio (PLR), mean platelet volume to lymphocyte ratio (MPVLR), and the systemic immune-inflammatory index (SII) have prognostic values in NMIBC treated with conventional intravesical chemotherapy or intravesical Chemohyperthermia (CHT) and the differences between them. A retrospective cohort study was conducted on 222 patients with NMIBC treated with Intravesical Chemotherapy or Intravesical CHT between January 2016 and December 2020. Within a week before surgery, PLR, MPVLR, and SII were determined based on routine blood settling. The optimal cutoff value of each index was determined using the receiver operating characteristic curve, and various groups were categorized accordingly. The factors influencing the prognosis of NMIBC patients receiving various treatments were investigated using the Kaplan- Meier survival curve and the Cox regression model. 69 cases (46.3%) in the gemcitabine (GEM) group had tumor recurrence and 19 (12.8%) of them progressed to muscle-invasive bladder cancer (MIBC) or got metastasis, while 19 cases (26.0%) in the CHT group recurred and 2 (2.7%) progressed. Elevated PLR, MPVLR, and SII were associated with higher recurrence rates in the GEM group. Meanwhile, PLR and MPVLR were the independent risk factors. While in the CHT group, high PLR and SII were related to postoperative recurrence and none of them were independent risk factors. The preoperative clinical inflammatory indexes PLR, SII, and MPVLR have certain predictive value for the postoperative recurrence-free survival (RFS) in NMIBC patients treated with intravesical chemotherapy while PLR and SII can predict the prognosis of NMIBC patients treated with intravesical CHT, which indicates that intravesical CHT may stop tumor recurrence by influencing the effect of mean platelet volume on tumor growth through some unknown mechanisms.

The clinical efficacy and safety of equipment-assisted intravesical instillation of mitomycin C after transurethral resection of bladder tumour in patients with nonmuscular invasive bladder cancer: A meta-analysis.

This review and meta-analysis aimed to systematically evaluate the clinical efficacy and safety of equipment-assisted intravesical instillation of mitomycin C (MMC) in patients with nonmuscular invasive bladder cancer (NMIBC) after transurethral resection of bladder tumour (TURBT). The Embase, PubMed, CNKI, CBM, WANGFANG, VIP, Cochrane Library, and Clinicaltrial.com databases were searched for articles published before April 2022. The experimental group was treated with intravesical instillation of MMC assisted by equipment, including radiofrequency-induced thermochemotherapy, conductive thermochemical therapy, electromotive drug administration, or locoregional hyperthermia. The control group was treated with simple MMC perfusion. The outcomes of interest in the meta-analysis were recurrence, progression, side-effects, gross haematuria, and bladder irritation. A total of 15 studies that enrolled 1,190 patients were included in the meta-analysis. Compared to that of the control group, device-assisted intravesical instillation of MMC significantly reduced both tumour recurrence (odds ratio [OR] = 0.32, 95% confidence interval [CI] [0.24, 0.42], P <0.00001) and progression (OR = 0.29, 95% CI [0.12, 0.67], P = 0.004). There were no significant differences between the two groups in terms of safety (OR = 1.21, 95% CI [0.66,2.21], P = 0.54), bladder irritation (OR = 1.06, 95% CI [0.72,1.55], P = 0.78), or gross haematuria (OR = 1.11, 95% CI [0.64,1.94], P = 0.72). Equipment-assisted intravesical instillation of MMC significantly reduced the recurrence and progression of patients with NMIBC who underwent TURBT and improved their quality of life. Given the significant heterogeneity in research quality and sample size among earlier studies, more prospective, multicentre, large sample randomized controlled trials are needed to supplement and verify this in the future.

Electromotive Enhanced Drug Administration in Oncology: Principles, Evidence, Current and Emerging Applications.

Simple SummarySince the 17th century, the use of electric currents to improve the transport of drugs into human tissues has been described. Currently, electrically driven drug transport is used in a variety of medicinal fields such as the urinary system, skin, eye and others. In this review, we summarize the principles and factors that govern electrically driven drug transport and discuss its current and emerging applications for the treatment of cancer patients.Local-regional administration of cytotoxic drugs is an important adjunct to systemic chemotherapy amongst cancer patients. It allows for targeted delivery of agents at high concentration to target sites while minimizing systemic side effects. Despite the pharmacokinetic advantages of the local–regional approach, drug transport into tumor nodules remains limited due to the biophysical properties of these tissues. Electromotive enhanced drug administration (EMDA) represents a potential solution to overcome challenges in local drug transport by applying electric currents. Through electrokinetic phenomena of electromigration, electroosmosis and electroporation, electric currents have been shown to improve drug penetration and distribution in a wide variety of clinical applications. Amongst patients with non-muscular invasive bladder cancer (NMIBC) and basal and squamous cell skin cancers, EMDA has been successfully adopted and proven efficacious in several pre-clinical and clinical studies. Its application in ophthalmological and other conditions has also been explored. This review provides an overview of the underlying principles and factors that govern EMDA and discusses its application in cancer patients. We also discuss novel EMDA approaches in pre-clinical studies and explore future opportunities of developments in this field.

Improvement of the bladder perfusion curative effect through tight junction protein degradation induced by magnetic temperature-sensitive hydrogels.

Postoperative intravesical instillation of chemotherapy is a routine procedure for non-muscular invasive bladder cancer (NMIBC). However, traditional bladder perfusion methods have insufficient exposure time, resulting in unsatisfactory therapeutic effects. In the present study, a chitosan (CS)-based in situ forming depot (ISFD) delivery system, including Fe3O4 magnetic nanoparticles (Fe3O4-MNP), CS, and β-glycerophosphate (GP) as main components, was synthesized. Pirarubicin (THP), as a chemotherapeutic drug, was loaded into the new system. Results showed that our carrier system (Fe3O4-THP-CS/GP) was converted into gel and attached to the bladder wall, possessing loose network structures with magnetic targeting and sustained release properties. Moreover, its retention time in bladder was more than 72 h accompanied by a suitable expansion rate and good degradation characteristics. The antitumor activities of Fe3O4-THP-CS/GP were more effective both in vitro and in vivo than the free THP solution. In the study of its mechanism, results showed that Fe3O4-THP-CS/GP suppressed the expression of occludin (OCLN) and affected tight junctions (TJ) between urothelial cells to promote THP absorption.

Preoperative Free Ferrous Protoporphyrin and Reactive Oxygen Species Status of Voided Urine Predicts Potential Recurrence Risk in NMIBC.

PurposeThis study aimed to assess the relationship between the preoperative reactive oxygen species and free ferrous protoporphyrin (ROS and FH) combined test and the risk of recurrence in a pathologically confirmed non-muscular invasive bladder cancer (NMIBC) patients.Patients and MethodsThe retrospective study included 218 patients, newly diagnosed with NMIBC between January 2019 and February 2022. According to the results of FH and ROS combined test of voided urine, all patients were classified as FH(-)/ROS(-), FH(+)/ROS(-), or FH(+) /ROS(+). We reviewed demographic information, pathological results, and the FH and ROS combined test status. The clinicopathological characteristics were evaluated, and the survival rates of each group were compared. Finally, we also analyzed the association between preoperative free ferrous protoporphyrin and reactive oxygen species status and the tumor stage and grade.ResultsThis study included 218 NMIBC patients with a median age of 68 years (interquartile range [IQR] 60–76 years). The number and proportion of patients in FH(-)/ROS(-), FH(+)/ROS(-) and FH(+) /ROS(+) were 95(43.6%), 79(36.2%) and 44(20.2%), respectively. And the pathological stages for those with FH(+) and ROS(+), FH(+) and ROS(-), FH(-) and ROS(-) at diagnosis were 0.5% Tis, 6.4% Ta, 13.3% T1; 2.3% Tis, 20.6% Ta, 13.3% T1; 5.5% Tis, 28.9% Ta, 9.2% T1, respectively. After adjusting for clinical factors, including tumor grade, tumor stage and FH/ROS status were independent risk factors for RFS In the multivariate Cox regression analysis. Through logistics regression analysis, FH(+)/ROS(+) were found to be corelated with high grade and more high stage (T1). Kaplan–Meier analysis showed that 1-year RFS of FH(+)/ROS(+), FH(+)/ROS(-) and FH(-)/ROS(-) were 46.0%, 87.8% and 93.4%, respectively (P=0.000).ConclusionIn newly diagnosed NMIBC patients, the status of FH(+)/ROS(+) has an association with a higher risk in recurrence. Furthermore, FH(+)/ROS(+) at diagnosis was correlated with high grade and higher stage (T1). Hence, the FH/ROS combined test can help specify treatment options for patients diagnosed with NMIBC.

Abstract 2085: The specific TLR3-agonist TL-532 induces life-long anti-tumor autovaccination, cross-immunity against unrelated cancers and reverses resistance to immune checkpoint inhibitors

Abstract Background: Toll-Like Receptor 3 (TLR3) is an innate immunity receptor that triggers inflammation by recognizing double stranded RNAs. In the past decades, TLR3-agonists have been used to fight cancer as inducer of type-I interferons and inducer of apoptosis specifically in tumor cells but not in normal cells. No TLR3-agonist has reached the market to date due to lack of manufacturing reproducibility, specificity, activity and/or due to toxicity. In this context, a new family of synthetic, specific and fully defined TLR3-agonist has been rationally designed (WO2019211492). Here we report the preclinical proof-of-concept of TL-532 in non-muscular invasive bladder cancer (NMIBC). Methods: In-vitro 2D and 3D cultures of J82 and RT4 NMIBC versus normal urothelial cells, were used. Freshly resected bladder tumors from patients were sliced and cultured ex vivo for 24 to 48h. In vivo experiments were performed using the ICI-resistant murine syngeneic/ectopic bladder cancer model MBT2, treated by intra- and peri-tumoral injections of TL-532. Results: We demonstrated in vitro, ex vivo and in vivo that TL-532 induced tumor cell death specifically by apoptosis, while it was well tolerated by normal cells, representing a broad in vitro safety margin. Ex vivo and in vivo, this tumor cell death was associated with a tumor microenvironment switch, evidenced by increases in antitumor biomarker secretion (IFN-α, IFN-λ1, IFN-γ, CCL5, CXCL9, CXCL10, CX3CL10), decreases in protumor biomarkers CCL22, sFAS and was associated in vivo with the recruitment and activation of conventional dendritic cells (cDCs) and cytotoxic T-lymphocytes (CTLs) at the tumor site. In vivo activity of TL-532 led to substantial tumor growth inhibition (88%) and delay (370%), translating in 35% complete response (CR) rate and 5.3-fold median survival benefit. Interestingly, among these CRs, 62% (13/21) showed life-long tumor auto-vaccination after 3 consecutive rechallenges at 3, 10 and 30 months. Remarkably, 54% (6/11) of the mice autovaccinated against bladder cancer also demonstrated cross-immunity against an unrelated and poorly immunogenic, syngeneic osteosarcoma cancer cell model (LM8). In addition, TL-532 treatment appeared to decrease the expression of the immune checkpoint PD-L1 on tumor cells ex-vivo and in cDCs in vivo and demonstrated a remarkable ability to reverse the anti-PD-L1 tumor-resistance when combined with the ICI leading to doubling of CR rate. Conclusion: We identified TL-532 as spearhead of a new rationally designed TLR3-agonist family. In monotherapy, it demonstrated substantial tolerance and promising anti-cancer and autovaccinal activity, which included unrelated cancers. TL-532 also demonstrated its remarkable ability to overcome ICI tumor-resistance, thus increasing the clinical landscape for ICI combination treatment. Citation Format: Marc Bonnin, Saïd Ourfali, Mathilde Boucard-Jourdin, Clémence Perret, Chloé Renoux, Nelly Vey, Marc Colombel, Bettina Werlé, Sylvain Thierry. The specific TLR3-agonist TL-532 induces life-long anti-tumor autovaccination, cross-immunity against unrelated cancers and reverses resistance to immune checkpoint inhibitors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2085.

Association between TOP2A, RRM1, HER2, ERCC1 expression and response to chemotherapy in patients with non-muscle invasive bladder cancer

PurposeThis study aimed to detect the expression levels of topoisomerase IIα (TOP2A), ribonucleotide reductase catalytic subunit M1 (RRM1),c-erbB-2 (HER2) and excision repair cross complementing group 1 (ERCC1) in non-muscular invasive bladder cancer (NMIBC) and explore the correlation between the expression of these genes and NMBIC sensitivity to pirarubicin or gemcitabine treatment. Materials and methodsNMIBC patient tissues and the bladder cancer cell lines BIU-87 and KK47 were selected for the exploration of drug sensitivity in vitro. Immunohistochemistry was used to examine protein expression in tissues. Reverse transcription-polymerase chain reaction (RT-qPCR) and a Western blot assay were used to detect the mRNA and protein levels in cells. The cell IC50 value was evaluated by an MTT assay. Flow cytometry was used to sort the cell subpopulations. ResultsIn the pirarubicin-treated group, the patients with high TOP2A expression experienced lower recurrence rates than those with low TOP2A expression, whereas TOP2A and HER2 co-expression resulted in higher recurrence rates. The patients with low RRM1 expression, especially those with low ERCC1 expression, experienced lower recurrence rates than the patients with high RRM1 expression in the gemcitabine-treated group. Tumour cells with high TOP2A expression were highly sensitive to pirarubicin, and TOP2A+ HER2- cells were more sensitive to pirarubicin than TOP2A+ HER2+ cells. Cells with low RRM1 expression levels were sensitive to gemcitabine, and RRM1−ERCC1- cells were more sensitive to gemcitabine than RRM1−ERCC1+ cells. ConclusionHigh TOP2A expression or low RRM1 expression could predict the sensitivity of NMIBC to pirarubicin or gemcitabine treatment. HER2 and ERCC1 expression may affect the effect of TOP2A and RRM1, thus affecting the efficacy of chemotherapeutic drugs.

EXPRESSION OF P53 PROTEIN ASSOCIATES WITH ANTI-PD-L1 TREATMENT RESPONSE ON HUMAN-DERIVED XENOGRAFT MODEL OF GATA3/CR5/6-NEGATIVE RECURRENT NONMUSCULAR INVASIVE BLADDER UROTHELIAL CARCINOMA

Annotation: The study investigated the prognostic role of p53 expression in patients with GATA3 / CR5 / 6-negative recurrent nonmuscular invasive bladder cancer on the background of anti-PD-L1 treatment using a xenograft model in immunodeficient BALB / c nu / nu mice obtained from a patient. Twenty lines of patient-derived xenografts of relapsed high-PD-L1(+) double-negative NMIBC were developed, of which 10 lines represented high-grade tumors and the other ones—low-grade bladder cancer. Acceptors of each grade-related branch received specific anti-PD-L1 antibodies. Animals’ survival, tumor-doubling time, and remote metastasis were followed during the post-interventional period. PD-L1, GATA3, CR5/6, and p53 protein expressions in engrafted tumors were assessed by immunohistochemistry. The expression of p53 protein is an independent factor affecting the animals’ survival time of anti-PD-L1-treated mice with low-grade high-PD-L1(+) double-negative nonmuscular invasive bladder cancer. P53 expression may be considered as a prognostic factor for the anti-PD-L1 treatment efficacy of low-grade high-PD-L1-positive GATA3(-)/CR5/6(-)-relapsed noninvasive bladder cancer.

Mycobacterium bovis bacille Calmette-Guerin-derived extracellular vesicles as an alternative to live BCG immunotherapy.

For over 40years, the gold standard treatment for non-muscular invasive bladder cancer (NMIBC) has been repeated administration of Mycobacterium bovis bacille Calmette-Guerin (BCG). Upon administration, BCG initiates a cascade of immunological events that lead to the recruitment of immune cells to the bladder that eliminates NMIBC cells in a multi-mechanistic, yet incompletely defined manner. Despite its effectiveness, live BCG immunotherapy is often impacted by limited supply and availability and can cause rare but serious side effects. Bacterial extracellular vesicles (EV) are nanoparticles secreted by live bacteria. EVs are composed of multiple surface proteins, sugars, and lipid that can elicit cellular responses and host recognition similar to live bacteria. In this study, we sought to evaluate the cellular responses of epithelial bladder cancer cells (BCC) to BCG EVs and live BCG. We compared the effect of each treatment on BCC cytokine production, cellular viability and apoptosis. Our data suggest that BCG EVs are as effective as live BCG in eliciting cytokine responses and halting cancer cell growth by, in part, inducing apoptosis. These results indicate that BCG EVs warrant investigation as an alternative to live BCG for NMIBC immunotherapy.

The Clinicopathological and Prognostic Value of NLR, PLR and MLR in Non-Muscular Invasive Bladder Cancer.

The clinicopathological and prognostic relevance of neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), and monocyte/lymphocyte ratio (MLR) in non-muscular invasive bladder cancer (NMIBC) was investigated. All patients who underwent transurethral resection of bladder tumor (TURBT) and postoperative intravesical chemotherapy had their peripheral blood levels of NLR, PLR, and MLR quantified. The preoperative peripheral blood levels of NLR, PLR, and MLR were analyzed in patients with G1, G2, and G3 NMIBC. A total of 208 patients was divided into poor prognosis (PP, with recurrence, n=51) and good prognosis (GP, no recurrence, n=157) groups, according to whether the recurrence of NMIBC was observed at 1-year follow-up after treatment. Univariate and multivariate logistic regression analyses were performed to evaluate the prognostic factors in NMIBC. In addition, receiver operating characteristic (ROC) curves were used to analyze the prognostic performance of NLR, PLR, and MLR in NMIBC. The preoperative peripheral blood level of PLR was significantly increased in patients with G3 NMIBC compared with that in patients with G1 (p < 0.05) and G2 NMIBC (p < 0.05). The results of univariate and multivariate logistic regression analyses showed that the tumor diameter, differentiation grade, and preoperative peripheral blood levels of NLR, PLR, and MLR were independent prognostic factors for NMIBC recurrence (p < 0.05). Compared with the NMIBC patients without recurrence, 3.490%, 177.575% and 3.175% were determined as the optimum prognostic cutoffs for NLR, PLR, and MLR, respectively. ROC curve was used to evaluate the sensitivity, specificity, and area under the curve (AUC) of NLR, PLR, MLR, and combinations. In contrast to NLR, PLR, or MLR, the combination of NLR, PLR, and MLR (AUC 0.758, sensitivity 66.70%, specificity 89.80%,Youden index 0.565) improved the prognostic performance in the discrimination of NMIBC patients with recurrence from thosewithout recurrence. The preoperative peripheral blood levels of NLR, PLR, and MLR, which were closely related to the grade and recurrence of NMIBC, were easy to detect and inexpensive. Moreover, these three factors showed the potential for auxiliary prognostic evaluation of NMIBC, wherein the combination than individual values exhibited better prognostic performance.

Photodynamic methods of treatment of nonmuscular-invasive bladder cancer

The review article is devoted to the application of photodynamic therapy for non-muscle invasive bladder cancer. The data on the mechanism and pathogenetic bases of the application of this method of treatment, the method of its implementation, the advantages and disadvantages of the photosensitizers and the results of clinical studies are presented. It has been shown that intraoperative photodynamic therapy significantly reduces the rate of recurrence of bladder cancer after transurethral resection, including in patients with carcinoma in situ and multifocal growth of urothelial tumors.

Endourological treatment of non-muscular-invasive bladder tumors

Background: Transurethral resection of the bladder is one of the essential methods in the diagnosis, treatment and management of non-muscularinvasive bladder cancer. The purpose of the procedure is to remove completely all visually detected tumors with a following establishment of a very precise histological diagnosis. The aim of the study is to compare the results of conventional transurethral endoscopic treatment and the En-bloc resection method using different types of energy sources in the treatment of bladder tumors. Material and methods: A total number of 88 patients underwent endourological interventions. Regarding the distribution, 23 patients had conventional transurethral resection, 22 – En-bloc monopolar resection, 21 – En-bloc bipolar resection and 22 – En-bloc with Thu:YAG laser. Clinical data, intraoperative and postoperative data and also the histopathological examination results were compared. Results: The compared groups were heterogeneous by age, sex, tumor characteristic (size, number, location). No significant differences were observed during the operations, comparing the intraoperative and postoperative complications of the studied groups. The detrusor musculature was detected in 74% of cases after conventional transurethral resection, in 91% of cases of En-bloc monopolar resection, in 95% of cases of En-bloc bipolar resection and in 96% of cases of En-bloc Thu:YAG laser. Conclusions: The En-bloc resection technique of non-muscular-invasive bladder tumors is a safe and effective method comparing with the conventional transurethral resection; it allows more favorable postoperative results and obtaining better quality tumor samples which allow establishing correct diagnosis of the disease.

A Systematic Review and Meta-Analysis Protocol of Chemoablation vs. Transurethral Resection of Bladder Tumor in Patients With Non-Muscle-Invasive Bladder Cancer.

Background: Bladder cancer is the second-ranked tumor of the genitourinary system. Transurethral resection of bladder tumor (TURBT) is currently the most important diagnosis and treatment method for non-muscular invasive bladder cancer (NMIBC). However, due to its high recurrence and progression rate, as well as high cost and inapplicability to some patients, intravesical chemoablation as an alternative to TURBT may be promising for NMIBC patients. However, there are very little data comparing its effectiveness, safety, best effective drug type, dosage selection, and cost with TURBT at present, which deserves further evaluation. The present study was designed in order to discuss which treatment is superior to another between chemoablation and TURBT in patients with NMIBC.Methods and Analysis: Databases including PubMed, MEDLINE, EMBASE, and Cochrane Library databases, as well as Chinese databases including CNKI (China national knowledge infrastructure), Wan Fang database, and Chinese Clinical Trial Registry, from August 1994 to the time when the official submission of this review was published was included in this review and screened by two reviewers (XS and DCF) independently. There were no language limitations. The study was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Data was analyzed using RevMan and Stata software. The primary aims were the clinical effectiveness, including response rate, complete response OS, CSM, recurrence rate, time to recurrent, progression rate, and time to progression, among others. The secondary aims mainly included safety and tolerability, including costs, operation time, hospital stay, bleeding volume, and complications, among others.Study Registration: This study is registered as PROSPERO CRD42021271124.

A nomogram combined with radiomics features, albuminuria, and metabolic syndrome to predict the risk of myometrial invasion of bladder cancer.

BackgroundTo establish a preoperative prediction model of myometrial invasion of bladder cancer (BC) based on the radiomics characteristics of multi-parameter thin-slice enhanced computed tomography (CT) imaging.MethodsData from 100 patients with BC were analyzed retrospectively. The patients were divided into two groups: muscular invasive BC and non-muscular invasive BC. The tumor region was segmented from enhanced CT images (arterial- and venous-phase calibration maps) of all patients using Slicer-3D software. We extracted 1,223 texture features from tumor image data based on the shape and gray-level co-occurrence matrix, gray size region matrix, gray run-length matrix, adjacent gray difference matrix, and gray correlation matrix. The patients were randomly divided into a training group (n=70) and a verification group (n=30) in a 7:3 ratio. Interclass correlation coefficients >0.75, least absolute shrinkage, and selection operator regression were used for feature selection. The prediction model was established by combining Rad-score, independent clinical factors, and support vector machine (SVM), and a radiomics nomogram was constructed. The nomogram was tested using the consistency index, calibration curve, time-dependent receiver operating characteristic curve, and clinical decision curve to predict the myometrial invasion of the bladder preoperatively.ResultsSix radiomics features that were significantly related to myometrial invasion of BC were selected to construct a predictive model. The area under the curve (AUC) values of training group and verification group based on SVM were 0.898 (95% CI: 0.820–0.976) and 0.702 (95% CI: 0.495–0.909), respectively. Single factor and multiple factor analysis showed that albuminuria (95% CI: 0.243–2.206, P=0.0014) and metabolic syndrome (95% CI: 0.850–2.935, P<0.001) were independent influencing factors of BC myometrial invasion. Clinical factors and 11 radiomics features were used to construct a comprehensive model for predicting the pathological grade of BC (radiomics + clinical). After a comprehensive comparison, we found that the overall effectiveness of the model (radiomics + clinical) was the highest (AUC =0.8457).ConclusionsBased on the multi-parameter thin-layer enhanced CT radiomics feature can be used as a potential independent predictor of BC myometrial invasion, the model based on parameters can initially quantitatively characterize the risk of myometrial invasion, and has excellent potential for predicting myometrial invasion of BC.

The predictive value of the ratio of the product of neutrophils and hemoglobin to lymphocytes in non-muscular invasive bladder cancer patients with postoperative recurrence.

PurposeThe purpose of this study was to explore the predictive value of the ratio of the product of neutrophils and hemoglobin to lymphocytes (NHL) in patients with non‐muscular invasive bladder cancer (NMIBC).Materials and MethodsWe retrospectively collected clinical and pathological data of patients with NMIBC who underwent transurethral resection of bladder tumor (TURBT) at our hospital between 2013 and 2018. The ratio of neutrophils to lymphocytes (NLR), the Systemic Immune Inflammation Index (SII), and NHL were obtained based on routine blood settlement within a week before surgery. The receiver operating characteristic curve was used to determine the optimal cutoff value of each index, and different groups were grouped accordingly. Kaplan‐Meier survival curve and Cox regression model were used to study the factors affecting the prognosis of NMIBC patients.ResultsThere was significant difference in recurrence‐free survival (RFS) rate between the high NLR group and the low NLR group, the high SII group and the low SII group, and the high NHL group and the low NHL group. Cox univariate regression analysis showed that tumor number, tumor size, tumor pathological grade, tumor pathological stage, NLR, SII, and NHL were related to postoperative RFS in patients with NMIBC. The tumor number, tumor pathological grade, SII, and NHL were independent predictors of RFS in multivariate analysis.ConclusionsThe preoperative clinical inflammatory indexes NLR, SII, and NHL have certain predictive value for postoperative RFS in NMIBC patients.