Induction and maintenance of sequential intravesical gemcitabine/docetaxel for intermediate and high-risk non-muscle invasive bladder cancer with different dosage protocols.

INTRODUCTION: The combination of sequential intravesical gemcitabine and docetaxel (Gem/Doce) chemotherapy has been considered a feasible option for BCG (Bacillus Calmette-Guérin) treatment in non-muscle invasive bladder cancer (NMIBC), gaining popularity during BCG shortage period. We seek to determine the efficacy of the treatment by comparing Gem/Doce induction alone vs induction with maintenance, and to evaluate the treatment outcomes of two different dosage protocols. METHODS: A bi-center retrospective analysis of consecutive patients treated with Gem/Doce for NMIBC between 2018 and 2023 was performed. Baseline characteristics, risk group stratification (AUA 2020 guidelines), pathological, and surveillance reports were collected. Kaplan-Meier survival analysis was performed to detect Recurrence-free survival (RFS). RESULTS: Overall, 83 patients (68 males, 15 females) with a median age of 73 (IQR 66-79), and a median follow-up time of 18 months (IQR 9-25), were included. Forty-one had an intermediate-risk disease (49%) and 42 had a high-risk disease (51%). Thirty-seven patients (45%) had a recurrence; 19 (23%) had a high-grade recurrence. RFS of Gem/Doce induction-only vs induction + maintenance was at 6 months 88% vs 100%, at 12 months 71% vs 97%, at 18 months 57% vs 91%, and at 24 months 31% vs 87%, respectively (log-rank, p < 0.0001). Patients who received 2 g Gemcitabine with Docetaxel had better RFS for all-grade recurrences (log-rank, p = 0.017). However, no difference was found for high-grade recurrences. CONCLUSION: Gem/Doce induction with maintenance resulted in significantly better RFS than induction-only. Combining 2 g gemcitabine with docetaxel resulted in better RFS for all-grade but not for high-grade recurrences. Further prospective trials are necessary to validate our results.

Comparative analysis of recurrence rates between intravesical gemcitabine and bacillus Calmette-Guérin induction therapy following transurethral resection of bladder tumors in patients with intermediate- and high-risk bladder cancer: A retrospective multicenter study.

PURPOSE: This study investigated the efficacy of intravesical gemcitabine as an alternative to bacillus Calmette-Guérin (BCG) therapy. MATERIALS AND METHODS: Data were retrospectively collected across seven institutions from February 1999 to May 2023. Inclusion criteria included patients with intermediate- or high-risk non-muscle invasive bladder cancer (NMIBC) who underwent transurethral resection of bladder tumors (TURBT) and received at least four sessions of intravesical gemcitabine or BCG induction therapy. Patient characteristics, complete remission (CR), occurrence, and progression rates were compared. RESULTS: In total, 149 patients were included in this study (gemcitabine, 63; BCG, 86). No differences were apparent between the two groups in baseline characteristics, except for the follow-up period (gemcitabine, 9.2±5.9 months vs. BCG, 43.9±41.4 months, p<0.001). There were no consistent significant differences observed between the two groups in the 3-month (gemcitabine, 98.4% vs. BCG, 95.3%; p=0.848), 6-month (94.9% vs. 90.0%, respectively; p=0.793) and 1-year CR rates (84.2% vs. 83.3%, respectively; p=0.950). Also, there was no significant statistical difference in progression-free survival between the two groups (p=0.953). The occurrence rates of adverse events were similar between the groups (22.2% vs. 22.1%; p=0.989); however, the rate of Clavien-Dindo grade 2 or higher was significantly higher in the BCG group (1.6% vs. 16.3%, respectively; p<0.001). CONCLUSIONS: Intravesical gemcitabine demonstrated efficacy comparable to BCG therapy for the first year in patients with intermediate- and high-risk NMIBC. However, long-term follow-up studies are warranted.

Enhancing Therapeutic Efficacy and Safety of Immune Checkpoint Inhibition for Bladder Cancer: A Comparative Analysis of Injectable vs. Intravesical Administration.

Bladder cancer (BC) presents a significant global health burden, characterized by high recurrence rates post-initial treatment. Gender differences in BC prevalence and response to therapy emphasize the importance of personalized treatment strategies. While Bacillus Calmette-Guérin (BCG) remains a cornerstone of BC therapy, resistance poses a challenge, necessitating alternative strategies. Immune checkpoint inhibitors (ICIs) have shown promise, yet systemic toxicity raises concern. Intravesical administration of ICIs offers a potential solution, with recent studies demonstrating the feasibility and efficacy of intravesical pembrolizumab. Although systemic toxicity remains a concern, its localized administration may mitigate adverse events. Additionally, liposomal delivery of ICIs exhibits promises in enhancing drug penetration and reducing toxicity. Novel imaging modalities compatible with Vesical Imaging-Reporting and Data System (VI-RADS) and capable of predicting high-grade bladder cancer can aid the pre-operative shared decision making of patient and surgeon. Future research should focus on refining treatment approaches, optimizing dosing regimens, and leveraging advanced imaging techniques to improve patient outcomes. In conclusion, intravesical immunotherapy presents a promising avenue for BC treatment, offering enhanced therapeutic effectiveness while minimizing systemic toxicity. Continued research efforts are essential to validate these findings and optimize intravesical immunotherapy's role in BC management, ultimately improving patient outcomes.

Multidisciplinary consensus document on the current treatment of bacille Calmette-Guérin-unresponsive non-muscle invasive bladder tumor.

Radical cystectomy is the current treatment of choice for patients with BCG-unresponsive non-muscle invasive bladder tumor (NMIBC). However, the high comorbidity of this surgery and its effects on the quality of life of patients require the investigation and implementation of bladder-sparing treatment options. These must be evaluated individually by the uro-oncology committee based on the characteristics of the BCG failure, type of tumor, patient preferences and treatment options available in each center. Based on FDA-required oncologic outcomes (6-month complete response rate for CIS: 50%; duration of response in responders for CIS and papillary: 30% at 12 months and 25% at 18 months), there is not currently a strong preference for one treatment over another, although the intravesical route seems to offer less toxicity. This work summarizes the evidence on the management of BCG-unresponsive NMIBC based on current scientific evidence and provides consensus recommendations on the most appropriate treatment.

Intravesical Injection of OnabotulinumtoxinA (Botulinum Toxin Type A) in Japanese Patients With Refractory Overactive Bladder.

BACKGROUND/AIM: Botulinum toxin intravesical injection therapy (hereafter, botulinum therapy) is approved in Japan for treating urinary urgency, frequency, and urinary incontinence due to refractory overactive bladder or neurogenic bladder. Although botulinum therapy is classified as urinary incontinence surgery, it is minimally invasive, effective, and safe. However, there are few reports on the actual use of botulinum therapy and examination of its effects and side-effects. Herein, we report real-world data on botulinum therapy. PATIENTS AND METHODS: Patients who received botulinum therapy for refractory overactive bladder at the Nara Medical University and affiliated facilities from May 2020 to May 2022 were enrolled. The patient background, treatment efficacy, and safety were retrospectively reviewed. RESULTS: Twenty-three cases of refractory overactive bladder (age: 68.4±14.1 years; 7 males, 16 females; 17 outpatient, 6 hospitalized) were enrolled. Pretreatment, the overactive bladder symptom score (OABSS) was 10.1±2.7, and post-void residual urine volume was 27.1±31.6 ml. Botulinum was administered once, twice, thrice, and four times in 11, eight, three, and one cases, respectively. OABSS decreased to 6.1±3.2 2 weeks after botulinum therapy (p<0.0001), and the effect persisted at 6.6±3.2 after 12 weeks (p<0.0001). Post-void residual urine volume increased to 74.6±79.2 ml after 2 weeks (p=0.0010), but subsequently improved to 33.9±42.0 ml after 12 weeks (p=0.0002). Adverse events included post-void residual urine volume of 200 ml or more in three patients (7.5%) and urinary retention grade 2 in two (5.0%). CONCLUSION: Botulinum therapy is effective and relatively safe for refractory overactive bladders.

Systemic versus localized Bacillus Calmette Guérin immunotherapy of bladder cancer promotes an anti-tumoral microenvironment: Novel role of trained immunity.

Treatment for higher-risk non-muscle invasive bladder cancer (NMIBC) involves intravesical immunotherapy with Bacillus Calmette Guérin (BCG); however, disease recurrence and progression occur frequently. Systemic immunity is critical for successful cancer immunotherapy; thus, recurrence of NMIBC may be due to suboptimal systemic activation of anti-tumor immunity after local immunotherapy. We previously reported that systemically acquired trained immunity (a form of innate immune memory) in circulating monocytes is associated with increased time-to-recurrence in patients with NMIBC treated with BCG. Herein, we used a mouse model of NMIBC to compare the effects of intravesical versus intravenous (systemic) BCG immunotherapy on the local and peripheral immune microenvironments. We also assessed whether BCG-induced trained immunity modulates anti-tumor immune responses. Compared with intravesical BCG, which led to a tumor-promoting immune microenvironment, intravenous BCG resulted in an anti-tumoral bladder microenvironment characterized by increased proportions of cytotoxic T lymphocytes (CTLs), and decreased proportions of myeloid-derived suppressor cells. Polarization toward anti-tumoral immunity occurred in draining lymph nodes, spleen, and bone marrow following intravenous versus intravesical BCG treatment. Pre-treatment with intravesical BCG was associated with increased rate of tumor growth compared with intravenous BCG pre-treatment. Trained immunity contributed to remodeling of the tumor immune microenvironment, as co-instillation of BCG-trained macrophages with ovalbumin-expressing bladder tumor cells increased the proportion of tumor-specific CTLs. Furthermore, BCG-trained dendritic cells exhibited enhanced antigen uptake and presentation and promoted CTL proliferation. Our data support the concept that systemic immune activation promotes anti-tumor responses, and that BCG-induced trained immunity is important in driving anti-tumor adaptive immunity.

Multiparametric Magnetic Resonance Imaging in the follow-up of non-muscle-invasive bladder tumors after intravesical instillations: a promising tool.

PURPOSE: The standard follow-up for non-muscle-invasive bladder cancer is based on cystoscopy. Unfortunately, post-instillation inflammatory changes can make the interpretation of this exam difficult, with lower specificity. This study aimed to evaluate the interest of bladder MRI in the follow-up of patients following intravesical instillation. METHODS: Data from patients who underwent cystoscopy and bladder MRI in a post-intravesical instillation setting between February 2020 and March 2023 were retrospectively collected. Primary endpoint was to evaluate and compare the diagnostic performance of cystoscopy and bladder MRI in the overall cohort (n = 67) using the pathologic results of TURB as a reference. The secondary endpoint was to analyze the diagnostic accuracy of cystoscopy and bladder MRI according to the appearance of the lesion on cystoscopy [flat (n = 40) or papillary (n = 27)]. RESULTS: The diagnostic performance of bladder MRI was better than that of cystoscopy, with a specificity of 47% (vs. 6%, p < 0.001), a negative predictive value of 88% (vs. 40%, p = 0.03), and a positive predictive value of 66% (vs. 51%, p < 0.001), whereas the sensitivity did not significantly differ between the two exams. In patients with doubtful cystoscopy and negative MRI findings, inflammatory changes were found on TURB in most cases (17/19). The superiority in MRI bladder performance prevailed for "flat lesions", while no significant difference was found for "papillary lesions". CONCLUSIONS: In cases of doubtful cystoscopy after intravesical instillations, MRI appears to be relevant with good performance in differentiating post-therapeutic inflammatory changes from recurrent tumor lesions and could potentially allow avoiding unnecessary TURB.

Treatment patterns and prognosis in patients with Bacillus Calmette-Guérin-exposed high-risk non-muscle invasive bladder cancer: a real-world data analysis.

PURPOSE: The International Bladder Cancer Group designated the subgroup that is resistant to Bacillus Calmette-Guérin (BCG) but does not meet the criteria for BCG-unresponsive NMIBC as "BCG-exposed high-risk NMIBC" to guide optimal trial design. We aimed to investigate the treatment patterns and prognoses of patients with BCG-exposed NMIBC. METHODS: We conducted a retrospective chart review of 3283 patients who received intravesical BCG therapy for NMIBC at 14 participating institutions between January 2000 and December 2019. Patients meeting the criteria for BCG-exposed and BCG-unresponsive NMIBC, as defined by the Food and Drug Administration and International Bladder Cancer Group, were selected. To compare treatment patterns and outcomes, high-risk recurrence occurring more than 24 months after the last dose of BCG was defined as "BCG-treated NMIBC." In addition, we compared prognoses between BCG rechallenge and early cystectomy in patients with BCG-exposed NMIBC. RESULTS: Of 3283 patients, 108 (3.3%), 150 (4.6%), and 391 (11.9%) were classified as having BCG-exposed, unresponsive, and treated NMIBC, respectively. BCG-exposed NMIBC demonstrated intermediate survival curves for intravesical recurrence-free and progression-free survival, falling between those of BCG-unresponsive and treated NMIBC. Among patients with BCG-exposed NMIBC, 48 (44.4%) received BCG rechallenge, which was the most commonly performed treatment, and 19 (17.6%) underwent early cystectomy. No significant differences were observed between BCG rechallenge and early cystectomy in patients with BCG-exposed NMIBC. CONCLUSIONS: The newly proposed definition of BCG-exposed NMIBC may serve as a valuable disease subgroup for distinguishing significant gray areas, except in cases of BCG-unresponsive NMIBC.

Effects of onabotulinum toxin-A injection on sexual function in women with refractory interstitial cystitis/bladder pain syndrome: A prospective study.

OBJECTIVES: To determine the effect of intravesical onabotulinum toxin-A (BoNT-A) treatment on sexual functions in female patients with refractory interstitial cystitis/bladder pain syndrome (IC/BPS). METHODS: Female patients with IC/BPS refractory to previous treatments were included in the study between January 2020 and April 2022. Patients were treated with the trigone-sparing injection (Group 1) or trigone-included injection (Group 2) techniques. 100 Units of BoNT-A was applied submucosally on 20 different points. The patients were evaluated with visual analog scale (VAS), O'Leary-Sant Interstitial Cystitis Symptom Index (ICSI), Interstitial Cystitis Problem Index (ICPI), Female Sexual Function Index (FSFI) questionnaires, 3-day voiding diary, uroflowmetry, and post-voiding residual volume analysis in the preoperative period, as well as on the 30th and 90th days postoperatively. For the repeated measurements, analysis of variance was used to assess the time-dependent variation across groups. RESULTS: The baseline FSFI score of the patients was 15.96 ± 3.82. Following the treatment, the FSFI scores were 22.43 ± 4.93 and 24.41 ± 5.94 on the 30th and 90th days, respectively (p < .001). We observed statistically significant improvement in all FSFI subdomains (p < .05). Statistically significant improvements with treatment on ICSI, ICPI, and VAS scores were achieved (p < .05). Preoperative FSFI scores were similar in Group 1 and Group 2 (p = .147). While the preoperative FSFI scores were 17.00 ± 3.73 and 14.84 ± 3.72 for Group 1 and Group 2, respectively, the scores after the treatment were 22.85 ± 5.01 and 21.98 ± 5.01 on the 30th day, and 24.62 ± 6.06 and 24.19 ± 6.05 on the 90th day postoperatively. Significant improvement was observed in FSFI scores with treatment, and no difference was observed between the two groups in terms of treatment response (p = .706). CONCLUSIONS: Intravesical BoNT-A injection in the treatment of women with refractory IC/BPS improves sexual functions. It also significantly improves pain and symptom scores. Both trigone-sparing and trigone-including injections are similarly safe and effective.

A Selective-Tumor-Penetrating Strategy via Unidirectional Direct Transfer for Intravesical Therapy of Bladder Cancer.

A selective tumor-penetrating strategy generally exploits tumor-targeted ligands to modify drugs so that the conjugate preferentially enters tumors and subsequently undergoes transcellular transport to penetrate tumors. However, this process shields ligands from their corresponding targets on the cell surface, possibly inducing an off-target effect during drug penetration at the tumor-normal interface. Herein, we first describe a selective tumor-penetrating drug (R11-phalloidin conjugates) for intravesical therapy of bladder cancer. The intravesical conjugates rapidly translocated across the mucus layer, specifically bound to tumors, and infiltrated throughout the tumor via direct intercellular transfer. Notably, direct transfer from normal cells to tumor cells was unidirectional because the pathways required for direct transfer, termed F-actin-rich tunneling nanotubes, were more unidirectionally extended from normal cells to tumor cells. Moreover, the intravesical conjugates displayed strong anticancer activity and well-tolerated biosafety in murine orthotopic bladder tumor models. Our study demonstrated the potential of a selective tumor-penetrating conjugate for effective intravesical anticancer therapy.

Hydrogel: a new material for intravesical drug delivery after bladder cancer surgery.

The standard treatment for non-muscle invasive bladder cancer (NMIBC) is transurethral resection of bladder tumor (TURBT). However, this procedure may miss small lesions or incompletely remove them, resulting in cancer recurrence or progression. As a result, intravesical instillation of chemotherapy or immunotherapy drugs is often used as an adjunctive treatment after TURBT to prevent cancer recurrence. In the traditional method, drugs are instilled into the patient's bladder through a urinary catheter under sterile conditions. However, this treatment exposes the bladder mucosa to the drug directly, leading to potential side effects like chemical cystitis. Furthermore, this treatment has several limitations, including a short drug retention period, susceptibility to urine dilution, low drug permeability, lack of targeted effect, and limited long-term clinical efficacy. Hydrogel, a polymer material with a high-water content, possesses solid elasticity and liquid fluidity, making it compatible with tissues and environmentally friendly. It exhibits great potential in various applications. One emerging use of hydrogels is in intravesical instillation. By employing hydrogels, drug dilution is minimized, and drug absorption, retention, and persistence in the bladder are enhanced due to the mucus-adhesive and flotation properties of hydrogel materials. Furthermore, hydrogels can improve drug permeability and offer targeting capabilities. This article critically examines the current applications and future prospects of hydrogels in the treatment of bladder cancer.

Effectiveness of integrated nursing interventions in enhancing patient outcomes during postoperative intravesical instillation for non-muscle invasive bladder cancer: A comparative study.

This study aimed to investigate nursing strategies for patients with non-muscle invasive bladder cancer (NMIBC) undergoing postoperative intravesical instillation. We recruited 100 NMIBC patients from January 2017 to January 2022. Participants were randomly assigned to either the research group or the control group (n = 50 each) using random number tables. The control group received routine nursing interventions, while the research group received integrated nursing interventions. We compared and analyzed various parameters, including patient satisfaction, treatment compliance, General Self-Efficacy Scale (GSES) scores, core quality of life scale scores, bladder carcinoma specificity scale scores, disease coping scores, and the incidence of complications among patients undergoing instillation treatment. The research group exhibited significantly higher satisfaction scores and treatment compliance (P < .05). Additionally, GSES, Self-Rating Anxiety Scale (SAS), and Self-Rating Depression Scale (SDS) scores were significantly improved in the research group (P < .05). Scores on each dimension of the EORTC QLQ-C30 were higher (P < .05). The research group also had lower scores for post-nursing urinary system diseases, treatment problems, future worries, and intestinal symptoms in the QLQ-BLS24 score (P < .05). Furthermore, the research group experienced fewer postoperative complications (P < .05). Nursing interventions significantly enhance the outcomes of NMIBC patients undergoing intravesical instillation treatment. These interventions effectively improve treatment compliance, alleviate negative emotions, modify coping strategies, reduce the incidence of complications, and enhance overall nursing satisfaction.

[Guillain-Barré syndrome caused by intravesical instillation of Bacillus Calmette-Guérin]. / Bacillus Calmette­Guérin intravesicalis instillációja által okozott Guillain­Barré-szindróma.

Introduction - Guillain-Barré syndrome (GBS) is an acute inflammatory demyelinating polyneuropathy. In the vast majority of patients, 1-4 weeks before the onset of GBS-related symptoms, an event such as upper respiratory tract or gastrointestinal tract infection, surgical intervention or vaccination is present. To the best of our knowledge, this is the first case of GBS that occurred after intravesical Bacillus Calmette-Guérin (BCG) therapy in the absence of tuberculosis or any other infection in the English literature.
Case report – A 65-year-old male patient, who had no systemic disorders except hypertension and coronary artery disease, underwent transurethral resection of a bladder tumour further to imaging studies investigating macroscopic haematuria. A pathologic examination revealed a non-muscle-invasive high-grade (pT1HG) transitional cell carcinoma. Immediately after the fourth cycle of intravesical BCG, which was administered 2 months after surgery, the patient experienced numbness and weakness in his lower and upper extremities, respectively. There were no signs or symptoms related to an acute cranial pathology or infectious disease. Nerve conduction studies, which were carried out on the 7th day after the onset of the neurologic symptoms, revealed a demyelinating sensorimotor polyneuropathy with mild secondary axonal damage in upper and lower limbs with a sural sparing pattern.
Conclusion - Without tuberculosis infection, GBS can occur secondary to increased immune response and antibodies triggered by intravesical BCG therapy. However, considering the worldwide use of BCG vaccination and thousands of intravesical BCG therapies, this is a very rare adverse effect. 

Intravesical Botulinum Toxin Injection Plus Hydrodistention Is More Effective in Patients with Bladder Pain-Predominant Interstitial Cystitis/Bladder Pain Syndrome.

Intravesical botulinum toxin A (BoNT-A) injections are included in the interstitial cystitis/bladder pain syndrome (IC/BPS) treatment guidelines. However, the IC phenotype suitable for treatment with BoNT-A has not been clarified. Therefore, we identified the factors influencing treatment outcomes for intravesical BoNT-A injections in patients with non-Hunner IC/BPS (NHIC). This retrospective study included patients with NHIC who underwent 100 U BoNT-A intravesical injections over the past two decades. Six months after treatment, treatment outcomes were assessed using the Global Response Assessment (GRA). Outcome endpoints included GRA, clinical symptoms, urodynamic parameters, urine biomarkers, and the identification of factors contributing to satisfactory treatment outcomes. The study included 220 patients with NHIC (42 men, 178 women). The satisfactory group (n = 96, 44%) had significantly higher pain severity scores and IC symptoms index, larger maximum bladder capacity (MBC), and lower 8-isoprostane levels at baseline. Logistic regression revealed that larger MBC (≥760 mL) and bladder pain predominance were associated with satisfactory outcomes after BoNT-A injection. Subjective parameters and pain severity scores improved significantly in patients with bladder pain-predominant IC/BPS after BoNT-A injection. Thus, NHIC patients with bladder or pelvic pain are more likely to experience satisfactory outcomes following intravesical BoNT-A injections.

Comparing Clinical Efficacy of Different Bacillus Calmette-Guérin Strains in Patients With T1 High Grade Bladder Cancer.

BACKGROUND/AIM: This study aimed to compare the clinical efficacy of two different Bacillus Calmette-Guérin (BCG) strains, TICE strain (OncoTICE) and Connaught strain (ImmuCyst), as a first line intravesical instillation therapy in patients with T1 high grade bladder cancer. PATIENTS AND METHODS: Patients with newly diagnosed T1 high-grade bladder cancer who underwent transurethral resection of bladder tumor (TURBT) followed by intravesical instillation therapy were enrolled. The effects of BCG strain on recurrence, progression, and side effects were analyzed using Kaplan-Meier and Cox proportional hazards models. RESULTS: Among 147 patients, 53 patients received Connaught strain and 94 patients received TICE strain. The completion rate of induction instillation was 92.45% in the Connaught group and 91.49% in the TICE group (p=1.00). The three-year recurrence-free survival rate was 71.7% in the Connaught group and 63.83% in the TICE group (p=0.33), whereas the three-year progression-free survival rate was 96.23% in the Connaught group and 89.36% in the TICE group (p=0.21). On Cox regression test, carcinoma in situ and ≥eight lesions were significant predictors for recurrence. No significant difference was observed in recurrence and progression between the two BCG regimens. The complication rates according to the Cleveland Clinic grading system showed no significant difference between the two groups (p=0.13). CONCLUSION: Both the Connaught and TICE strains of BCG demonstrated comparable three-year recurrence-free survival rates and three-year progression-free survival rates for T1 high grade bladder cancer, as well as comparable adverse events. Due to the global BCG shortage, further strain comparisons are essential for clinical validation.

Time to progression is the main predictor of survival in patients with high-risk nonmuscle invasive bladder cancer: Results from a machine learning-based analysis of a large multi-institutional database.

BACKGROUND: In patients affected by high-risk nonmuscle invasive bladder cancer (HR-NMIBC) progression to muscle invasive status is considered as the main indicator of local treatment failure. We aimed to investigate the effect of progression and time to progression on overall survival (OS) and to investigate their validity as surrogate endpoints. METHODS: A total of 1,510 patients from 18 different institutions treated for T1 high grade NMIBC, followed by a secondary transurethral resection and BCG intravesical instillation. We relied on random survival forest (RSF) to rank covariates based on OS prediction. Cox's regression models were used to quantify the effect of covariates on mortality. RESULTS: During a median follow-up of 49.0 months, 485 (32.1%) patients progressed to MIBC, while 163 (10.8%) patients died. The median time to progression was 82 (95%CI: 78.0-93.0) months. In RSF time-to-progression and age were the most predictive covariates of OS. The survival tree defined 5 groups of risk. In multivariable Cox's regression models accounting for progression status as time-dependent covariate, shorter time to progression (as continuous covariate) was associated with longer OS (HR: 9.0, 95%CI: 3.0-6.7; P < 0.001). Virtually same results after time to progression stratification (time to progression ≥10.5 months as reference). CONCLUSION: Time to progression is the main predictor of OS in patients with high risk NMIBC treated with BCG and might be considered a coprimary endpoint. In addition, models including time to progression could be considered for patients' stratification in clinical practice and at the time of clinical trials design.

Prevention of Bladder Cancer Recurrence With the Botanical Formula LCS103: A Case Series Study.

Despite effective chemotherapy and other available oncology treatments, recurrence rates for non-muscle invasive bladder cancer (NMIBC) remain high, with as many as 60% of patients requiring repeat intravesical treatments with BCG or other agents within a 24-month period. The botanical formula LCS103 has displayed anti-cancer activity on bladder cancer cells, though its clinical efficacy remains to be proven. A consecutive series of 30 patients with bladder cancer was examined retrospectively, of which a cohort of 20 patients (18 with NMIBC, 2 with metastatic disease) was treated with LCS103 for between 14 months and 16 years, in addition to their conventional oncology care. Only 3 patients (15%) had a single tumor recurrence after initiation of the botanical treatment, as opposed to pre-treatment recurrence reported among 11 patients (55%; range, 1-5). The majority of LCS103-treated patients reported reduced severity for urological symptoms (pain, frequency, and urgency on urination; and nocturia), as well as for weakness and fatigue, and for general wellbeing. No adverse events were associated with use of the botanical formula. Further prospective randomized trials are needed to confirm and better understand these initial findings.

Urease-powered nanobots for radionuclide bladder cancer therapy.

Bladder cancer treatment via intravesical drug administration achieves reasonable survival rates but suffers from low therapeutic efficacy. To address the latter, self-propelled nanoparticles or nanobots have been proposed, taking advantage of their enhanced diffusion and mixing capabilities in urine when compared with conventional drugs or passive nanoparticles. However, the translational capabilities of nanobots in treating bladder cancer are underexplored. Here, we tested radiolabelled mesoporous silica-based urease-powered nanobots in an orthotopic mouse model of bladder cancer. In vivo and ex vivo results demonstrated enhanced nanobot accumulation at the tumour site, with an eightfold increase revealed by positron emission tomography in vivo. Label-free optical contrast based on polarization-dependent scattered light-sheet microscopy of cleared bladders confirmed tumour penetration by nanobots ex vivo. Treating tumour-bearing mice with intravesically administered radio-iodinated nanobots for radionuclide therapy resulted in a tumour size reduction of about 90%, positioning nanobots as efficient delivery nanosystems for bladder cancer therapy.

Anatomical location and number of injection sites of intravesical OnabotulinumtoxinA for females with refractory idiopathic overactive bladder: A scoping review.

AIMS: The negative impact on quality of life and the economic-related burden to the patient and the health care system associated with idiopathic overactive bladder (iOAB) is well-documented. Intradetrusor OnabotulinumtoxinA (BTN/A) injections are a well-used treatment modality for the management of overactive detrusor refractory to medical management, with well-documented efficacy and safety profiles. There is currently no best practice guideline for the administration of BTN/A for this procedure and historically the trigone of the bladder has been excluded from the injection paradigm given the risk of vesicoureteral reflux (VUR). METHODS: A scoping review methodology was employed to assess available literature to evaluate current techniques used. There is emerging literature that the inclusion of the trigone may increase the efficacy of the procedure, while maintaining a similar adverse effect profile. Similar results could also be obtained by decreasing the number of injection sites. A scoping review was completed with systematic methodology using the Preferred Systematic Reviews and Meta Analyses extension for Scoping Review checklist. The search strategy looked to evaluate BTN/A and number of injection sites and the inclusion of the trigone in female patients with iOAB. Studies with male or neurogenic bladder only were excluded. Mixed studies were included. A specialist research librarian was engaged, with supervision from a functional urologist using a combination of MeSH and natural language terms. Two investigators independently reviewed the titles and abstracts. RESULTS: Twelve articles were included and were published between 2005 and 2021. There was no evidence of VUR in any of the results. All but one study reported similar if not improved efficacy of trigone-inclusion. Lower number of injection sites had similar efficacy profiles to higher numbers of intradetrusor injections. CONCLUSIONS: Further high-quality randomized control trials of trigone inclusion and reduction of injection sites are required. It is hoped that with further exploration of intraoperative methods for BTN/A injections, the development of universally accepted guidelines may optimize management and experiences for patients with iOAB.