Despite the efficacy of onabotulinumtoxinA, its safety profile remains a concern. This meta-analysis reviewed the major adverse events (AEs) associated with intravesical onabotulinumtoxinA treatment in patients with neurogenic detrusor overactivity (NDO) and idiopathic overactive bladder (iOAB). Randomized controlled trials (RCTs) conducted between January 2000 and December 2022 were searched for adult patients administered different onabotulinumtoxinA dosages or onabotulinumtoxinA vs. placebo. Quality assessment was performed using the Cochrane Collaboration tool, and statistical analysis was performed using Review Manager version 5.3. A total of 26 RCTs were included in the analysis, including 8 on NDO and 18 on iOAB. OnabotulinumtoxinA vs. placebo significantly increased the urinary tract infection (UTI) incidence in patients with NDO (relative risk, or RR, 1.54) and iOAB (RR, 2.53). No difference in the RR with different onabotulinumtoxinA dosages was noted. Urinary retention was frequent with onabotulinumtoxinA use in the NDO (RR, 6.56) and iOAB (RR, 7.32) groups. Similar observations were made regarding the risks of de novo clean intermittent catheterization (CIC). The risk of voiding difficulty increased with onabotulinumtoxinA use in patients with iOAB. Systemic AEs of onabotulinumtoxinA, including muscle weakness (RR, 2.79) and nausea (RR, 3.15), were noted in patients with NDO; most systemic AEs had a low incidence and were sporadic.

Neurogenic lower urinary tract dysfunction is caused by various disorders of the central and peripheral nervous system. This can result in several malfunctions of the storage and voiding phase, which are reflected in symptoms such as urgency, urinary incontinence, recurrent urinary tract infections and post-void residual urine. Reduced quality of life, impairment of the upper urinary tract, reduced employment opportunities and worsening of the symptoms of the underlying condition can be the consequences. Therefore, the primary goals of neuro-urology are to protect the upper urinary tract, maintain continence and improve the quality of life of those affected. To achieve these goals, different intravesical drug and electrophysical therapy options are available. These article addresses these intravesical therapy options as well as their indication and relevance in neuro-urology.
Die Ursache der neurogenen Dysfunktion des unteren Harntraktes sind verschiedenste Schädigungen des zentralen und peripheren Nervensystems. Daraus können diverse Störungen von Harnspeicher- und Harnentleerungsfunktion der Blase entstehen, die sich in Symptomen wie Drangbeschwerden, Harninkontinenz, rezidivierenden Harnwegsinfekten und Blasenentleerungsstörungen äußern. Lebensqualitätseinschränkungen, Gefahr für den oberen Harntrakt, Einschränkung der Erwerbsfähigkeit und Verschlechterung der Symptome der Grunderkrankung sind häufig die Folge. Ziel der Neuro-Urologie ist daher, neben dem Schutz des oberen Harntraktes, Kontinenz zu erhalten bzw. wiederherzustellen und die Lebensqualität der Betroffenen zu verbessern. Dazu stehen neben oraler Medikation und operativen Maßnahmen auch medikamentöse und elektrophysikalische intravesikale Therapieoptionen zur Verfügung. Die Übersicht geht daher auf diese intravesikalen Therapieverfahren sowie deren Indikation und Stellenwert in der Neuro-Urologie ein.

BACKGROUND: Intravesical treatment for non-muscle invasive bladder cancer (NMIBC) aims to reduce recurrences and stop progression. Hyperthermia-enhanced chemotherapy with devices like COMBAT BRS, Unithermia, and BR-TRG-I is a promising alternative to conventional Bacillus de Calmette Guerin (BCG) therapy.
OBJECTIVE: To systematically review the efficacy of hyperthermia generated by conduction devices in the treatment of NMIBC.
METHODS: The review followed the preferred reporting items for systematic reviews and meta-analyses guidelines. A search was performed in the PubMed, Cochrane Library, Scopus, and ClinicalTrials.gov databases. Two reviewers independently assessed the eligibility of candidate studies and abstracted data from studies that met the inclusion criteria. The primary endpoint was assessment of recurrence. Secondary objectives included evaluation of treatment progression and safety.
RESULTS: Thirty studies meeting inclusion criteria underwent data extraction. In intermediate-risk NMIBC patients, COMBAT versus mitomycin C (MMC) in normothermia revealed no superiority in reducing recurrence or progression. High-risk NMIBC patients using COMBAT achieved similar or superior outcomes to BCG. BR-TRG-I demonstrated superior results over normothermia in intermediate- and high-risk NMIBC patients. Unithermia proved less effective than BCG in high-risk NMIBC. Progression outcomes were promising with COMBAT and BR-TRG-I, but comprehensive analysis was limited due to inconsistent assessment across studies. Adverse events were primarily mild-moderate, with some device-specific differences.
CONCLUSIONS: Studies on conduction hyperthermia present great variability, which do not allow us to determine the superiority of 1 device over another in terms of recurrence, progression, and/or adverse effects. Further research with consistent administration protocols is crucial for definitive conclusions.

OBJECTIVE: Urinary retention is a common adverse effect after intravesical injection of onabotulinum toxin A (BTX) for overactive bladder (OAB). Reported retention rates range from 1.6% to more than 40%. This variation may be due to varying definitions of retention in the literature.
OBJECTIVE: We aimed to assess the variation in definitions of urinary retention across studies of BTX for the treatment of OAB.
METHODS: We performed a systematic review of studies of BTX for OAB by querying MEDLINE and EMBASE according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We included original research studies on adults with overactive bladder treated with BTX and urinary retention reported as an outcome from January 2000 to December 2020.
RESULTS: From 954 results, we identified 53 articles that met inclusion criteria. There were 6 definitions for urinary retention. The majority of studies (60.4%) reported initiating clean intermittent catheterization (CIC) as the metric for retention. Five (9.5%) studies provided no definition despite reporting retention as an adverse event. Twenty studies (37.7%) specified a postvoid residual volume (PVR) threshold for initiating CIC in asymptomatic patients; 19 (35.8%) specified a PVR threshold for CIC in symptomatic patients. The PVR thresholds ranged from 100 to 400 mL. Twenty-three studies (43.4%) did not address asymptomatic elevation of PVR, and 22 (41.5%) did not address how symptomatic patients were managed.
CONCLUSIONS: Urinary retention after BTX injection is inconsistently defined in the literature. Lack of standardization in reporting retention after intravesical BTX prevents accurate assessment of the risk of urinary retention and comparison of outcomes between studies.

BACKGROUND: Local therapies for high risk non-muscle-invasive bladder cancer (NMIBC) such as intravesical chemotherapy (IVC) have shown a high rate of progression and recurrence. Intravesical Bacillus Calmette-Guérin (BCG) for local therapies has been shown to reduce progression and recurrence in patient with NMIBC. However, its potential role is limited in high burden countries for tuberculosis (TB) due to its low specificity that can cause wrong diagnosis or false positive in patients with clinically diagnosed tuberculosis. BCG vaccine that has to be given for most people in tuberculosis endemic countries will induce trained immunity that could reduce the effectivity of intravesical BCG for NMIBC. Moreover, intravesical BCG is contraindicated in patient with or previous tuberculosis. The potential clinical benefit of intraarterial chemotherapy (IAC) in delaying the recurrence and progression of high-risk NMIBC have been investigated with promising results. We aimed to conduct a meta-analysis to evaluate the potential anti-tumor effect of IAC in NMIBC.
METHODS: We conducted a comprehensive search of published articles in Cochrane Library, Pubmed, and Science-Direct to identify relevant randomized controlled trials (RCTs) and observational studies comparing IAC alone or combined with IVC versus IVC/BCG alone in NMIBC. The protocol of preferred reporting items for systematic review and meta-analysis (PRISMA) was applied to this study.
RESULTS: Four RCTs and 4 cohort observational studies were eligible in this study and 5 studies were included in meta-analysis. The risk ratio of tumor recurrence was reduced by 35% (RR = 0.65; 95% CI 0.49-0.87; p = 0.004) in IAC plus IVC, while recurrence-free survival (RFS) was prolonged by 45% (HR: 0.55; 95% CI, 0.44-0.69; p < 0.001). The risk of tumor progression was reduced by 45% (RR = 0.55; 95% CI 0.41-0.75; p = 0.002) and tumor progression-free survival (PFS) was also prolonged by 53% (HR: 0.47; 95% CI, 0.34-0.65; p<0.001). Some RCT\'s had high or unclear risk of bias, meanwhile 4 included cohort studies had overall low risk of bias, therefore the pooled results need to be interpreted cautiously. Subgroup analysis revealed that the heterogeneity outcome of tumour recurrence might be attributed to the difference in NMIBC stages and grades.
CONCLUSIONS: The IAC alone or combined with IVC following bladder tumor resection may lower the risk of tumor recurrence and progression. These findings highlight the importance of further multi institutional randomized controlled trials with bigger sample size using a standardized IAC protocol to validate the current results.

OBJECTIVE: 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.

Aim: We aimed to review the evidence of reducing the dose or number of BCG instillations in non-muscle invasive bladder cancer (NMIBC) patients. Material & methods: A literature search was done according to Preferred Reporting Items for Meta-Analyses statement. Results: Overall, 15 and 13 studies were eligible for qualitative and quantitative synthesis, respectively. In patients with NMIBC, lowering either the dose or number of BCG instillations increases the risk of recurrence, but not the risk of progression. Lowering the dose of BCG decreases the risk of adverse events compared with standard-dose BCG. Conclusion: Standard-dose and -number of BCG is preferred for NMIBC patients based on oncologic efficacy; however, low-dose BCG could be considered in selected patients who suffer from significant adverse events.
Doctors use a medicine called BCG to treat a kind of bladder cancer that hasn\'t spread to other parts of the body. But because there isn\'t enough of this medicine, scientists are looking at giving smaller amounts. They found that smaller amounts of the medicine have fewer side effects, but they also found that they might not work as well to stop the cancer from coming back. So, the regular amount of BCG is still the best option for most patients, but smaller amounts might be okay for some people who are worried about side effects. However, more research is needed to make sure it\'s safe and effective.

The prognosis and safety of continuous saline bladder irrigation (CSBI) after transurethral resection of bladder tumor (TURB) as an alternative method needs to be explored. A literature review and meta-analysis were performed by searching PubMed, EMBASE, Cochrane Library databases and original references of the included articles. PRISMA checklists were followed. We used the GRADEpro GDT to assess the certainty of evidence from the results of our meta-analysis. A total of eight articles including 1600 patients were studied. The results indicated that patients received CSBI after TURB had no statistical differences compared to the control group in the recurrence-free survival and progression-free survival. However, the CSBI group showed significant improvements compared to the control group in terms of the number of recurrences during follow-up and the period to first recurrence except for the number of tumor progression during follow-up. Furthermore, patients treated with CSBI did not show an inferior effect than those treated with immediate intravesical chemotherapy (IC) in respects of recurrence-free survival, progression-free survival, the number of recurrences during follow-up, the number of tumor progression during follow-up and the period to first recurrence. But the immediate IC group had a higher incidence than the CSBI group in terms of macrohematuria, micturition pain, frequency of urination, dysuria, retention and local toxicities. Patients treated with CSBI after TURB showed a significant improvement compared to the control group in terms of the number of recurrences during follow-up and the period to first recurrence. However, compared to immediate IC, CSBI did not show an inferior effect except for lower incidence of adverse reactions.PROSPERO registration number CRD42021247088.

To assess the oncologic outcomes and the safety profile of a reduced-dose versus full-dose BCG regimen in patients with non-muscle-invasive bladder cancer (NMIBC).
We performed a systematic review according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The PubMed, Embase, and Web of Science databases were searched in January 2022 for studies that analyzed oncological outcomes and compared between reduced- and full-dose BCG regimens.
Seventeen studies including 3757 patients met our inclusion criteria. Patients who received reduced-dose BCG had significantly higher recurrence rates (OR 1.19; 95%CI, 1.03-1.36; p = 0.02). The risks of progression to muscle-invasive BC (OR 1.04; 95%CI, 0.83-1.32; p = 0.71), metastasis (OR 0.82; 95%CI, 0.55-1.22; p = 0.32), death from BC (OR 0.80; 95%CI, 0.57-1.14; p = 0.22), and all-cause death (OR 0.82; 95%CI, 0.53-1.27; p = 0.37) were not statistically different. When restricting the analyses to randomized controlled trials, we found similar results. In subgroup analysis, reduced dose was associated with a higher rate of BC recurrence in studies that used only an induction regimen (OR 1.70; 95%CI, 1.19-2.42; p = 0.004), but not when a maintenance regimen was used (OR 1.07; 95%CI, 0.96-1.29; p = 0.17). Regarding side effects, the reduced-dose BCG regimen was associated with fewer episodes of fever (p = 0.003), and therapy discontinuation (p = 0.03).
This review found no association between BCG dose and BC progression, metastasis, and mortality. There was an association between reduced dose and BC recurrence, which was no longer significant when a maintenance regimen was used. In times of BCG shortage, reduced-dose regimens could be offered to BC patients.

Intravesical bacillus Calmette-Guérin (BCG) is a common and highly effective treatment for non-muscle invasive urothelial carcinoma of the urinary bladder. BCG may cause an autoimmune reaction in some patients. One hundred and fifty-eight papers were analyzed, for a total of hundred and thirty patients with reactive arthritis, sixty patients with ocular manifestations and eighteen patients with other rheumatologic diseases. Among 130 subjects with reactive arthritis, an autoimmune symptom occurred after 5 instillations of intravesical BCG (IQR 4-6), which represents 5 weeks in most cases. Fifty-one patients had concurrent ocular involvement. The resolution of symptoms was achieved in a median of 32.5 days (IQR 14-90). Forty-two men and twenty women had ocular manifestations, most commonly conjunctivitis. Patients with HLA-B27 typing had earlier presentation of ocular symptoms related to the number of instillations (4.5 vs 6 [p < 0.05]. Resolution of symptoms was achieved at a median of 128 days (IQR 21-150). Among patients treated with NSAIDs (either with or without steroids), the duration of the disease was significantly shorter in both the articular and the ocular groups (28 vs. 120 [p < 0.05] and 30 vs.105 [p < 0.05], respectively). Other autoimmune manifestations included general autoimmune diseases, such as vasculitis, psoriasis and myasthenia gravis.