Intravesical Chemotherapy Research Articles

The Roles of miRNAs in Predicting Bladder Cancer Recurrence and Resistance to Treatment.

Bladder cancer (BCa) is associated with significant morbidity, with development linked to environmental, lifestyle, and genetic causes. Recurrence presents a significant issue and is managed in the clinical setting with intravesical chemotherapy or immunotherapy. In order to address challenges such as a limited supply of BCG and identifying cases likely to recur, it would be advantageous to use molecular biomarkers to determine likelihood of recurrence and treatment response. Here, we review microRNAs (miRNAs) that have shown promise as predictors of BCa recurrence. MiRNAs are also discussed in the context of predicting resistance or susceptibility to BCa treatment.

Adjuvant Intravesical Chemotherapy Versus Immunotherapy for All Risk Groups of Patients With Non-muscle Invasive Bladder Cancer.

The treatment strategy for non-muscle invasive bladder cancer (NMIBC) has not changed significantly over the past 30 years. Chemotherapeutic agents (mitomycin-C, epirubicin, etc.) and BCG (Bacillus Calmette-Guerin) immunotherapy are used as adjuvant intravesical therapy. To compare the difference between adjuvant chemotherapy and adjuvant immunotherapy in their efficacy of reducing the number of tumor recurrences. In this prospective clinical study, which included 99 patients with NMIBC from March 2018.-March 2023., we publish the results for all risk groups of patients treated with intravesical chemotherapy Epirubicin or with BCG immunotherapy, after TURBT (Trans urethral resection of bladder tumor) within 1 year. Patients were stratified into 2 groups. The first group was treated with Epirubicin (1 dose within 24 hours of surgery, then 6 weekly instillations and 3 maintenance doses), and the second group was treated with BCG (2-3 weeks after TURBT 6 weekly instillations, and 3 maintenance doses). The monitoring period was 24 months. In patients treated with intravesical chemotherapy, recurrence occurred in 9 patients (17.64%), and in patients treated with BCG, recurrence occurred in 7 patients (14.58%). A similar incidence of disease recurrence was observed in both groups (p=0.787). The results of our study show a similar therapeutic response by risk groups of patients treated with chemotherapy and immunotherapy. Since BCG production will cease in the future, the task of urologists is to introduce intravesical chemotherapy into wider use and to modernize it as a safe and effective method of adjuvant treatment for non-muscle-invasive bladder cancer.

Hyperthermia Improves Doxorubicin-Based Chemotherapy by Activating Mitochondrial Apoptosis in Bladder Cancer

Purpose: Although intravesical chemotherapy has several antitumoral benefits, it can also have severe side effects. The development of novel therapeutic approaches for bladder cancer (BC) is thus warranted. Hyperthermia (HT) is a widely applicable adjuvant therapy in various cancers. Therefore, this study investigated the effect of HT on improving the chemosensitivity of BC. Materials and Methods: The BC cell lines 5637 and T24 were cultured and treated with HT (43°C) for 24 h. Then, cell viability and survival were assessed using resazurin reagent and colony formation assay, respectively. Western blot assay was used to analyze the levels of Bax, Bcl-2, cleaved caspase-3, and cleaved poly (ADP-ribose) polymerase (PARP) protein expression. Mitochondria degradation was observed by MitoTracker Green staining. Results: In BC cells, HT co-administered with various concentrations of doxorubicin significantly inhibited cell viability and survival. Moreover, HT combined with doxorubicin promoted mitochondrial apoptosis, which caused Bax upregulation and Bcl-2 downregulation. Levels of cleaved caspase-3 and PARP protein expression were also elevated after co-treatment. Conclusion: Taken together, HT improved the chemosensitivity of BC cells to doxorubicin. HT combined with chemotherapy further activated mitochondrial apoptosis in BC cells. The findings suggested that HT may serve as a potential adjunctive treatment for BC that is ready to be applied clinically.

A systematic review on the available treatment modalities for Bacillus Calmette-Guérin-unresponsive carcinoma in situ and tumors in patients who are ineligible for or decline radical cystectomy.

Globally, urothelial bladder carcinoma is a disease which carries a poor prognosis. There are various treatment modalities for urothelial bladder carcinoma with intravesical Bacillus Calmette-Guérin immunotherapy being the most efficacious intravesical therapy and the treatment of choice for patients with carcinoma in situ. A number of chemotherapeutic drugs are also available for the management of Ta/T1 tumors such as mitomycin C and epirubicin. However, relapse and progression is quite common. The optimal management of patients with Bacillus Calmette-Guérin-unresponsive disease remains to be a challenge. The purpose of this study was to conduct a systematic review on the treatment modalities available for the management of Bacillus Calmette-Guérin-unresponsive carcinoma in situ and urothelial bladder carcinoma in patients who are ineligible or decline radical cystectomy. Two authors independently searched three databases on the treatment modalities available for the management of Bacillus Calmette-Guérin-unresponsive carcinoma in situ and Bacillus Calmette-Guérin-unresponsive urothelial bladder carcinoma. The systematic search resulted in 15 studies. We recommend the use of intravesical CG0070 adenovirus or hyperthermic intravesical chemotherapy mitomycin C in patients with carcinoma in situ only disease. In patients with carcinoma in situ ± Ta/T1 disease, we recommend the use of intravesical radiofrequency-induced chemohyperthermia or electromotive drug administration of mitomycin C. In patients who have Ta/T1 disease, we recommend the use of either hyperthermic intravesical chemotherapy epirubicin or electromotive drug administration mitomycin C followed by chemohyperthermia mitomycin C. If any of these second line therapies fail, an alternative regimen would be a combination of gemcitabine, cabazitaxel, and cisplatin. This recommendation is subject to the available resources and clinical expertise available in different hospitals. More studies using study designs such as randomized controlled trials comparing multiple drugs with larger sample sizes and regular follow-up intervals should be performed to accurately assess the different medications and aid in designing guidelines to guide the management of Bacillus Calmette-Guérin-unresponsive non-muscle invasive intravesical bladder cancer.

Retracted: Efficacy of Bladder Intravesical Chemotherapy with Three Drugs for Preventing Non‐Muscle‐Invasive Bladder Cancer Recurrence

Retracted: Efficacy of Bladder Intravesical Chemotherapy with Three Drugs for Preventing Non‐Muscle‐Invasive Bladder Cancer Recurrence

Characteristics of Non-Muscle Invasive Bladder Cancer (NMIBC) in Patients Treated in an Indonesian Tertiary Hospital from 2008 to 2019

Bladder cancer is the 10th most common cancer in both males and females with a ratio of 3:1. About 75% of bladder cancers are non-muscle invasive bladder cancers (NMIBC). The aim of this study was to identify the characteristics of Non-Muscle Invasive Bladder Cancer (NMIBC) patients treated in Dr. Hasan Sadikin General Hospital as one of the tertiary hospitals in Indonesia. This was a retrospective descriptive study that involved reviewing the medical records of patients diagnosed with NMIBC between January 2008 and December 2019. Characteristics reviewed were age, gender, body mass index (BMI), smoking history, urinary tract infection and stone history, intravesical chemotherapy and its side effects, and urinary cytology results. All data were tabulated and charted. Fifty-one out of 773 bladder cancer patients were diagnosed with NMIBC (6.59%). The mean age was 62.94 years old, with the majority of patients were in the 60-69 age group (31.37%). Males constituted the majority of the patients (n=44, 86.27%), with most patients had ideal BMI (66.66%), smoking history (72.54%), urinary tract infection history (56,86%), and urolithiasis history (5.88%). Thirty patients were given intravesical chemotherapy (58.82%), three patients experienced hematuria (10%), and four patients had painful urination (13.33%). Urinary cytology showed atypical cells (92.16%) in the majority of patients. The incidence of NMIBC in bladder cancer patients in our study was 6.59%, which differs from the incidence in developed countries of 75%, as shown in previous literature.

Novel Therapies for High-Risk Non-Muscle Invasive Bladder Cancer.

The treatment options for high-risk non-muscle invasive bladder cancer (NMIBC), particularly following BCG, remain limited. We highlight recent, promising therapies for high-risk NMIBC. Several therapies utilizing different mechanisms of action have demonstrated favorable results in the BCG-naïve and BCG-unresponsive settings. These treatments include intravenous and intravesical immunotherapy, viral- and bacterial-based intravesical therapies, combination intravesical chemotherapy regimens, and novel intravesical chemotherapy administration. Overall, the efficacy and tolerability of emerging treatments for NMIBC appear promising and provide potential alternatives to radical cystectomy. As the landscape of managing BCG-unresponsive disease evolves, clinical trials will explore future options and determine effective alternatives.

How to Perform Intravesical Chemotherapy after Second TURBT for Non-Muscle-Invasive Bladder Cancer: A Single-Center Experience

The objective of this study aimed to explore whether the original IVC regimen should be continued after the second TURBT or whether the IVC induction phase should be restarted from the beginning. A retrospective analysis was performed on 137 patients who underwent a second TURBT at the Affiliated Hospital of Xuzhou Medical University between April 2014 and June 2022. Based on the pathological findings, patients were divided into two groups: group A patients, who did not have a residual tumor on pathological examination after the second TURBT; and group B patients, who had residual tumor. Recurrence was determined using cystoscopy and imaging every three months. The endpoint was recurrence-free survival. In the entire cohort, there was a statistically significant difference in the RFS between patients in the two IVC regimens (p = 0.029). The RFS of patients in group B1 was significantly lower than that of patients in group B2 (p = 0.009). There was no significant difference in RFS between the subgroups A1 and A2 (p = 0.560). Multivariate Cox regression analysis confirmed that the IVC regimen after a second TURBT (p = 0.012) and T stage after a second TURBT (p = 0.005) were both independent predictors for patient RFS. If the pathological findings of the second TURBT specimen is benign, patients can continue their previous treatment regimen without restarting an IVC induction phase. Unnecessary IVC can be avoided in these patients. In contrast, for patients with residual tumors in the second TURBT specimen, the need to restart the IVC induction phase should be emphasized to improve patient prognosis.

Development and investigation of a novel device with gemcitabine for hyperthermic intravesical chemotherapy

Purpose To evaluate the safety and efficacy of a novel hyperthermic intravesical chemotherapy (HIVEC) device in combination with gemcitabine. Materials and methods A pilot clinical trial was performed on patients with high-risk non-muscle invasive bladder cancer (NMIBC), who received HIVEC via the novel device (BR-PRG). Treatment regimen included eight weekly instillations of intravesical GEM (3 g in 150 mL normal saline [NS]) at a temperature of 45 °C for 60 min. Assessment of adverse events (AEs) was the primary objective of the trial. Disease recurrence and the thermal stability of GEM were also analyzed. Results A total of 116 HIVEC treatments were delivered. Fifteen and eighteen patients were included in the effectiveness and safety analysis, respectively. Median follow-up was 12 months; five patients experienced a disease recurrence. One-year cumulative incidence of recurrence was 23.8% in EORTC intermediate risk group and 37.5% in high-risk group. Ten patients experienced at least one AE, with the most common being acute urinary tract infection, followed by urinary tract pain, and hematuria. Two patients experienced acute cystitis (grade 3 AE) and instillations were postponed until full recovery. Other AEs were minor, and no systemic toxicity was observed. The contents of GEM in solution of 0.9% NS or NS mixed with artificial urine were stable at 25 °C, 37 °C, 43 °C, 45 °C, 47 °C and 50 °C for 2 h. Conclusion GEM can be an ideal drug for use in HIVEC due to its good thermal stability. BR-PRG, combined with GEM was safe and effective in administering HIVEC.

Hyperthermic intravesical chemotherapy with mitomycin-C for the treatment of high-risk non-muscle-invasive bladder cancer patients.

The objectives of the study are to explore tolerability, acceptability and oncological outcomes for patients with high-risk non-muscle-invasive bladder cancer (NMIBC) treated with hyperthermic intravesical chemotherapy (HIVEC) and mitomycin-C (MMC) at our institution. Our single-institution, observational study consists of consecutive high-risk NMIBC patients treated with HIVEC and MMC. Our HIVEC protocol included six weekly instillations (induction), followed by two further cycles of three instillations (maintenance) (6 + 3 + 3) if there was cystoscopic response. Patient demographics, instillation dates and adverse events (AEs) were collected prospectively in our dedicated HIVEC clinic. Retrospective case-note review was performed to evaluate oncological outcomes. Primary outcomes were tolerability and acceptability of HIVEC protocol; secondary outcomes were 12-month recurrence-free, progression-free and overall survival. In total, 57 patients (median age 80.3 years) received HIVEC and MMC, with a median follow-up of 18 months. Of these, 40 (70.2%) had recurrent tumours, and 29 (50.9%) had received prior Bacillus Calmette-Guérin (BCG). HIVEC induction was completed by 47 (82.5%) patients, but only 19 (33.3%) completed the full protocol. Disease recurrence (28.9%) and AEs (28.9%) were the most common reasons for incompletion of protocol; five (13.2%) patients stopped treatment due to logistical challenges. AEs occurred in 20 (35.1%) patients; the most frequently documented were rash (10.5%), urinary tract infection (8.8%) and bladder spasm (8.8%). Progression during treatment occurred in 11 (19.3%) patients, 4 (7.0%) of whom had muscle invasion and 5 (8.8%) subsequently required radical treatment. Patients who had received prior BCG were significantly more likely to progress (p = 0.04). 12-month recurrence-free, progression-free and overall survival rates were 67.5%, 82.2%, and 94.7%, respectively. Our single-institution experience suggests that HIVEC and MMC are tolerable and acceptable. Oncological outcomes in this predominantly elderly, pretreated cohort are promising; however, disease progression was higher in patients pretreated with BCG. Further randomised noninferiority trials comparing HIVEC versus BCG in high-risk NMIBC are required.

Efficacy and adverse reactions of intra-arterial chemotherapy in patients with bladder cancer: A systematic review and meta-analysis.

This meta-analysis investigated the efficacies of intra-arterial chemotherapy (IAC) plus intravesical chemotherapy (IVC) versus IVC alone in patients with non-muscle-invasive bladder cancer (NMIBC), and preoperative IAC versus preoperative intravenous chemotherapy (IV) in patients with bladder cancer. We also assessed the adverse reactions (ARs) of IAC. We searched the PubMed, Embase, Cochrane Library, and Web of Science databases for English articles published before April 2021. The qualities of cohort studies and randomized controlled trials were analyzed using the Newcastle-Ottawa Scale and Cochrane risk-of-bias tool, respectively. Effect outcomes were computed by random-effects and fixed-effects models. Statistical analyses were conducted using Stata 16.0 and RevMan v5.3.0. A total of seven articles were included. The analysis revealed that IAC plus IVC significantly prolonged recurrence-free survival (RFS) (hazard ratio [HR] = 0.55, 95% confidence interval [CI] = 0.40-0.76, I2 = 0%) and progression-free survival (PFS) (HR = 0.59, 95% CI = 0.37-0.97, I2 = 0%) compared with IVC alone in NMIBC patients after transurethral resection of bladder tumor (TURBT), but had no effect on overall survival (OS), tumor recurrence interval, or tumor-specific death rate. Preoperative IAC had no significant OS benefit compared with preoperative IV in bladder cancer patients. Regarding ARs, patients treated with IAC were significantly more likely to develop grade 1-2 ARs, including nausea/vomiting (odds ratio [OR] = 26.38, 95% CI = 1.88-370.79, I2 = 78%), neutropenia (OR = 10.15, 95% CI = 3.01-34.24, I2 = 0%), hypoleukemia (OR = 5.49, 95% CI = 1.38-21.82, I2 = 26%), and increased alanine aminotransferase (OR = 12.28, 95% CI = 2.24-67.43, I2 = 0%), but there was no significant difference between grade 1-2 ARs and grade 3-4 ARs in terms of increased creatinine in patients treated with IAC. Therefore, administration of IAC plus IVC after TURBT improved RFS and PFS compared with IAC alone in patients with NMIBC. IAC was associated with mild ARs and was well tolerated by most patients.

Partial cystectomy: Review of a single center experience from 2004 to 2019.

Partial cystectomy (PC) is a bladder sparing option to treat bladder cancer in a carefully selected group of patients. We sought to analyze outcomes of partial cystectomy (PC) in a contemporary cohort of patients at a single institution. Records were reviewed for 43 patients with a primary urothelial carcinoma (UC) who had a partial cystectomy with curative intent at Columbia University Medical Center from 2004 to 2019. Endpoints of interest were noninvasive recurrence (defined as any recurrent nonmuscle invasive disease), advanced recurrence (defined as a muscle invasive recurrence or metastasis), and death. We used unadjusted Cox proportional hazards regressions and log rank tests to estimate the association between clinical characteristics and endpoints of interest. Among 43 patients with bladder cancer treated with partial cystectomy, median patient age was 73 years (interquartile range 67-77.5) and 86% were male. Twenty-three percent of patients received preoperative neoadjuvant chemotherapy (NAC) and 49% of patients were given perioperative intravesical chemotherapy at the time of PC. Pathologic stage was <T2 for 23 (53%) patients and ≥T2 for 20 (47%) patients. Pathology showed 14% of patients had lymph node involvement, and 9% had positive surgical margins. Mean follow-up was 51 months (range 1-176). Five-year overall survival was 78%. Of 43 patients, 23 patients (53%) had no recurrence, 9 patients (21%) experienced noninvasive intravesical recurrence, and 11 patients (26%) experienced advanced recurrences. Two patients (5%) required salvage radical cystectomy and 8 patients (19%) died of bladder cancer. On univariate analysis, lymphovascular invasion (hazard ratio [HR] 4.4, confidence interval [CI] 1.3-14.3), pathological stage (HR 5.9, CI 1.3-27.4), and NAC (HR 6.5, CI 1.9-22.7) were associated with advanced recurrence. Noninvasive recurrence was associated with not receiving perioperative intravesical chemotherapy (HR 0.7, CI 0.1-6.0). In well-selected patients, partial cystectomy offers adequate local control of bladder cancer. The risk of systemic progression is similar to reported case series of RC.

Novel Therapeutic Strategies for BCG-unresponsive Non-muscle Invasive Bladder Cancer

Development of therapeutic strategies for non-muscle-invasive bladder cancer (NMIBC) that failed intravesical Bacillus Calmette - Guerin (BCG) therapy remains an urgent priority for clinicians. Currently, radical cystectomy is the recommended standard of care treatment options for these patients. Intravesical chemotherapy using gemcitabine and docetaxel are regarded as the most effective treatment options for unresponsive NMIBC, however, these options are ineffective in the control of bladder cancer. In this review, we present the definition of BCG unresponsive NMIBC and discuss about the recent management options that include immunotherapy, intravesical chemotherapy, gene therapy, and targeted individualized therapy. Notably, immunotherapy is the most recent strategy utilizing the PD-1/PD-L1 and other immune checkpoint inhibitors (ICIs). Pembrolizumab (KEYNOTE-057), Atezolizumab (SWOG S1605) and Nivolumab were developed and are efficacious in BCG –unresponsive NMIBC. In summary, ICIs are considered as the most promising agent for BCG unresponsive NMIBC in the future.

Initial experience with surrounding en bloc transurethral resection of bladder tumor and simultaneous intravesical treating for non-muscle invasive bladder cancer

PurposeThe high recurrence rate after traditional transurethral resection of bladder tumor (TURBT) remains a challenge for management of non-muscle invasive bladder tumor (NMIBC). The aim of this study was to evaluate feasibility, efficacy and safety of surrounding en bloc resection using a general wire bipolar loop electrode and simultaneous intravesical chemotherapy.MethodsWe retrospectively analyzed data of 111 consecutive patients with NMIBC treated from June 2018 to December 2021. These patients underwent conventional TURBT and immediate intravesical chemotherapy (n = 45) or surrounding en bloc TURBT and simultaneous intravesical chemotherapy in the Urology Department of Harbin Medical University Cancer Hospital, The former and latter were defined as the conventional TURBT group and the surrounding en bloc TURBT group, respectively. All patients were followed up from 6 to 40 months, with an average of 24 months. Demographic characteristics, location and number of tumors, perioperative and postoperative data, pathological results and recurrence were documented.ResultsThere were no significant differences in clinicopathological data between the conventional TURBT group (n = 45) and the surrounding en bloc TURBT group (n = 66). Operative time and complications associated with TURBT were comparable in the two groups. Recurrent tumors were found during follow-up in 2 (3.0%) of 66 patients in the surrounding en bloc group and 9 (20%) of 45 patients in the conventional group (p < 0.05). Lower urinary tract symptoms developed in 2 (3.0%) of 66 patients after surrounding en bloc TURBT and in 11(24.4%) of 45 patients after conventional TURBT (p < 0.05).ConclusionSurrounding en bloc TURBT and simultaneous intravesical chemotherapy might significantly decrease the recurrence rate of NMIBC, and showed favorable safety and tolerability profiles. The general bipolar loop electrode was appropriate to complete the procedure.

Conductive hyperthermic chemotherapy versus electromotive drug administration of mitomycin C as intravesical adjuvant treatment of patients with intermediate or high-risk non-muscle invasive bladder cancer

BackgroundDevices that increase the penetration of intravesical chemotherapeutic agents have been developed as alternatives to the use of bacillus Calmette–Guérin, in short supply at a time of increasing global incidence of non-muscle invasive bladder cancer (NMIBC).We performed a prospective observational study to compare 2 of these devices in the treatment of patients with high- and intermediate-risk NMIBC. The primary endpoint was the recurrence-free rate. Secondary endpoints were the rate of progression and adverse events. MethodsAfter undergoing transurethral bladder resection, 98 patients were selected to receive 1 of 2 treatments: hyperthermic intravesical chemotherapy (HIVEC) treatment with 40 mg of mitomycin C (MMC) using Combat BRS System V2.0 at 43 ± 0.5°C and 200 ml/min for 60 minutes (56 patients) or electromotive drug administration (EMDA) with 40 mg of MMC at 20 mA for 30 minutes (42 patients). The treatment schemes were similar: 6 weekly instillations as induction and 6-monthly instillations as maintenance. The recurrence rates were evaluated at 6 and 12 months and the progression rates at 12 months. ResultsThe recurrence-free rate at 12 months was 91,1% in the HIVEC group and 88.1% in the EMDA group (P ≥ 0.05). After the 12-month follow-up, only 1 progression occurred in each treatment group. In terms of adverse events, no significant differences were found between the treatments. ConclusionsHIVEC and EMDA techniques are comparable in terms of recurrence, progression and adverse events at 12 months in the treatment of patients with high- and intermediate-risk NMIBC.

R11 modified tumor cell membrane nanovesicle-camouflaged nanoparticles with enhanced targeting and mucus-penetrating efficiency for intravesical chemotherapy for bladder cancer.

Intravesical chemotherapy is generally used in the clinic for treating bladder cancer (BCa), but its efficacy is limited due to the permeation barrier and side effects caused by the off-targeting of normal urothelial cells. In this study, BCa cell-derived membrane nanovesicles were used as drug carriers, and their homologous tumor-targeting capacity was utilized. A BCa-targeting hendeca-arginine peptide was functionalized onto the nanovesicles to impart a mucus-penetrating ability and thus overcome the permeation barrier. The tumor-targeting and mucus-penetrating nanovesicles were stable in urine, were highly permeable to the glycosaminoglycan layer, and specifically targeted BCa. The vesicles were internalized through caveolin-mediated endocytosis, were transported to nonlysosome-localized intracellular regions, and efficiently infiltrated bladder tumor spheroids. In in vivo intravesical chemotherapy, the nanovesicles achieved chemo-resection in murine orthotopic BCa models. This BCa-targeting and mucus-penetrating drug delivery system may be promising for the intravesical chemotherapy of BCa.

Enhancement of human bladder carcinoma cell chemosensitivity to Mitomycin C through quasi-monochromatic blue light (λ=453±10nm).

Human urothelial bladder carcinoma (uBC) is the second most tumor entity of the urogenital tract. As far as possible, therapy for non-muscle invasive uBC takes place as resection of the tumor tissue, followed by intravesical chemotherapy or immunotherapy. Because of the high recurrence rate of uBC, there is a need for improved efficiency in the treatment. In the present in vitro study we have evaluated a new approach to enhance the cytotoxic efficiency of Mitomycin C (MMC), which is commonly used for intravesical treatment of uBC on the relevant urothelial cancer cell line RT112. For that we used quasi-monochromatic blue light (453±10nm) at its non-toxic dose of 110J/cm2 as an additive stimulus to enhance the therapeutic efficiency of MMC (10μg/ml). We found, that blue light exposure of RT112 cells led to a very strong increase in intracellular production of reactive oxygen species (ROS) and to a significant reduction (p<0.05) of all function parameters of mitochondrial respiration, including basal activity and ATP production. Although not being toxic when used as a single impact, together with MMC blue light strongly enhanced the therapeutic efficiency of MMC in the form of significantly enhanced cytotoxicity via apoptosis and secondary necrosis. Our results clearly show that blue light, most likely due to its ability to increase intracellular ROS production and reduce mitochondrial respiration, increased the cytotoxic efficiency of MMC and therefore might represent an effective, low-side-effect, and success-enhancing therapy option in the local treatment of bladder cancer.

Instillation Strategies for Non-Muscle-Invasive Bladder Cancer in the Bacillus Calmette-Guerin Shortage Era: A Simple Solution for BCG Discontinuation.

Among intravesical instillation protocol in patients with non-muscle-invasive bladder cancer (NMIBC), chemotherapy agents have been widely used during the bacillus Calmette-Guérin (BCG) shortage era since the patient might under the risk of BCG discontinuation. This study evaluates the efficacy of incomplete BCG instillation compared with pure chemotherapy instillation protocol. Patients newly diagnosed with intermediate- and high-risk NMIBC who received incomplete BCG intravesical instillation or chemotherapy instillation were retrospectively included. Patients were divided into three groups according to different intravesical instillation schedules: [BCG only], [BCG + Chemo], and [Chemo only]. Comparisons between these three groups were performed. Bladder recurrence-free survival (RFS) was analyzed as the primary endpoint. A total of 475 patients who received intravesical instillations were enrolled. Compared to the [Chemo only] group, the [BCG + Chemo] group had significantly better bladder RFS (p = 0.027). Multivariate analysis of recurrence revealed the [BCG + Chemo] regimen has a hazard ratio 0.381 (95% CI 0.154-0.941, p = 0.037). The total instillation number >12 was associated with better RFS (p = 0.001) compared with other instillation numbers. For NMIBC patients facing the risk of unexpected BCG instillation interruption, instead of starting instillation with chemotherapy agents, receiving BCG first till stoppage then shifting to chemotherapy agents is recommended.

Efficient Delivery of P3H4 siRNA and Chlorin e6 by cRGDfK-Installed Polyarginine Nanoparticles for Tumor-Targeting Therapy of Bladder Cancer.

Purpose: Prolyl 3-hydroxylase family member 4 (P3H4) is a potent prognostic oncogene in bladder cancer (BC), and the inhibition of P3H4 suppresses BC tumor growth. This study aimed to evaluate the efficiency of P3H4 inhibition for BC tumor therapy via tumor-targeting nanoparticles. Methods and results: A linear polyarginine peptide (R9) was synthesized, azide-modified, and then assembled with cyclic pentapeptide cRGDfK. Chlorin e6 (ce6)-conjugated CH3-R9-RGD nanoparticles were prepared for the delivery of siP3H4 into T24 cells in vitro and BC tumors in vivo. Dynamic light scattering analysis identified that the optimum CH3-R9-RGD@siP3H4 molar ratio was 30/1. CH3-R9-RGD@ce6/siP3H4 nanocomposites decreased P3H4 expression and cell proliferation and promoted reactive oxygen species production, apoptosis, and calreticulin exposure in T24 cells in vitro. In vivo experiments showed that CH3-R9-RGD@ce6/siP3H4 nanocomposites caused pathological changes, suppressed BC tumor growth, promoted caspase 3 expression, and enhanced calreticulin exposure in tumor cells. Conclusions: The tumor-targeting CH3-R9-RGD nanocomposites encapsulating siP3H4 and ce6 might be an alternative therapeutic strategy or intravesical instillation chemotherapy for BC.

Improving the Quality of Transurethral Resection of Bladder Tumour (TURBT) Operative Notes Following the European Association of Urology Guidelines: A Completed Audit Loop Study.

BackgroundThe European Association of Urology (EAU) recommends that the operative steps and documentation necessary for successful and appropriate management of bladder cancer include identifying factors necessary to assign disease risk stratification, clinical stage, adequacy of resection and the presence of complications and immediate intravesical chemotherapy administration.AimTo assess and improve the adequacy of current transurethral resection of bladder tumour (TURBT) documentation at a district general hospital in the UK against the EAU 2022 guidelines.MethodsOperative notes over a one-year period were assessed for the inclusion of key steps to achieve a comprehensive TURBT as outlined by EAU guidelines. Outcomes included documentation on the details of the operative findings and intervention as well as the perioperative assessment. A standardised template for TURBT procedures was created and surgical staff received training on its usage. The audit was subsequently repeated after six months to assess for improvements.ResultsTURBT documentation of 78 cases in the first cycle was compared to 37 cases from the second cycle. Significant improvements in the documentation of tumour size (46% to 89%; p<0.05), tumour description (59% to 89%; p <0.05), depth of resection (36% to 89%; p<0.05), administration of chemotherapy (21% to 46%; p<0.05) and assessment for perforation (22% to 68%; p=0.001) were demonstrated. Improvements in pre-operative and post-operative examination rates under anaesthesia also achieved statistical significance (47% & 14% respectively to 89%; p<0.05). There was an increase in the documentation of completeness of resection but this did not achieve statistical significance (59% to 68%; p=0.42).ConclusionThe operative note template led to the improvement in the documentation, improving the risk stratification of bladder cancer in patients undergoing TURBT. The use of procedure-specific operative note templates should be adopted for all commonly performed procedures to improve the completeness of documentation.