The Potential Role of Urinary Microbiota in Bladder Carcinogenesis: A Systematic Review.

PURPOSE: The quantitative objective of the current systematic review was to identify the potential role of urinary microbiota in bladder cancer (BC) carcinogenesis, invasiveness, progression, and metastasis. MATERIALS AND METHODS: The proposed systematic review was conducted in accordance with critical review according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement, and the Joanna Briggs Institute (JBI) methodology for systematic reviews. The search strategy aimed to find both published and unpublished studies up to the January 2024. A JBI appraisal checklist was used to assess possible biases. RESULTS: This systematic review was centered on 27 studies comprising 926 BC patients. Overall, 412 control individuals were compared with BC patients. The most common sampling method was midstream urine collection. Regarding microbial alpha diversity, there was no statistically significant difference between cancerous and healthy samples (n=8), recurrent and not recurrent (n=1), responders versus non-responders(n=1), tumor grades (n=1), and collection methods (n=1). However, five studies reported higher diversity in controls, and five other studies reported, conversely, high levels of alpha diversity in BC patients or recurrent cases. Furthermore, a responder (RE) to treatment and a non-muscle invasive bladder cancer (NMIBC) groups demonstrated significant difference with non-responder (NR) and muscle invasive bladder cancer (MIBC), respectively. In terms of beta-diversity, nine studies reported significant diversity between BC patients and controls, one article demonstrated difference between recurrent and not recurrent patients, a study reported significant difference in RE and NR groups whereas another showed opposite, and others (n=4) did not find any difference between BC, controls, MIBC and NMIBC patients, or between tumor grades. One study reported a difference between the collection method and beta-diversity in males and another reported the difference in females. CONCLUSION: The included studies demonstrate that the composition of urinary microbiota is altered in patients with BC. However, the differentially enriched genera in the urine of these patients vary between studies, and there is too much heterogeneity across studies to make any reliable and valid conclusions. Furthermore, well-designed research is necessary to assess the role of microbiota in the carcinogenesis and progression of BC.

Genitourinary Fistula: 5 Years' Experience of Five Referral Centers in Iran.

INTRODUCTION AND HYPOTHESIS: Genitourinary fistula is a devastating ailment that has an impact on women's physical health, mental health, emotional health, and financial security. The management of genitourinary fistula depends on the type, size, and duration of fistula formation. The purpose of this study is to report the features of genitourinary fistula in Iranian women and our experience in the management of fistula. METHODS: Retrospective chart reviews of 283 patients were performed to determine the cause of the fistula, prior repairs, tissue interposition, and the success rate. The operation was considered successful if the patient did not have any urine leakage during the observation time. RESULTS: The mean (SD) age of women was 49.51 (19.39; range: 21-70) years, Of these, 137 (52.9%) had a history of previous genitourinary fistula surgery. The average fistula was 1.53 (0.041) cm in size. The median (interquartile range) operation lasted 70 (15) min. The success rate after fistula repair was 91.5%. The typical follow-up period lasted 13.26 (range: 1-88) months. Forty-three (15.2%) patients had a big fistula (>2.5 cm) and 4 patients (1.4%) had a history of pelvic radiation therapy, among other reasons for failure. After a second repair, all patients' initial failures were resolved. There were no significant complications, as classified by Clavien-Dindo class 2 or greater. Additionally, there were no bowel, ureteral, or nerve injuries. CONCLUSIONS: Our patients with genitourinary fistula had a successful outcome following repair techniques, without any significant morbidity or mortality.

Primary retroperitoneal lymph node dissection for clinical stage II seminoma: A systematic review and meta-analysis of safety and oncological effectiveness.

To evaluate the oncological outcomes and safety of primary retroperitoneal lymph node dissection (RPLND) in patients with clinical stage (CS) II seminomatous testicular germ cell tumor (TGCT). A literature search using PubMed, Scopus, and Cochrane Library was conducted on July 2023 to identify relevant studies according to the Preferred Reporting Items for Systematic Review and Meta Analysis (PRISMA) guidelines. The pooled recurrence rate and treatment-related complications were calculated using a random effects model. Overall 8 studies published between 1997 and 2023 including a total of 355 patients were selected for systematic review and meta-analysis with the overall median follow-up of 38 months. The overall and infield recurrence rate were 0.14 (95% CI: 0.08-0.22) and 0.04 (95% CI: 0.00-0.11), respectively. The overall pooled rate of ≥ Clavien Dindo grade III complications was 0.04 (95% CI: 0.01-0.10); there was no significant heterogeneity (I^2 = 35.10%, P = 0.19). Antegrade ejaculation was preserved with the overall pooled rate of 0.98 (95% CI: 0.95-1.00); there was no significant heterogeneity on Chi-square and I2 tests (I^2 = 0.00%, P = 0.58). Primary RPLND is a safe and effective treatment option for patients with CS II seminomatous TGCT resulting highly promising cure rates combined with low treatment-associated adverse events, at medium-term follow-up. However, owing to the lack of comparative studies to the current standard of care and the limited follow-up, individual decision must be made with the informed patient in a shared decision process together with a multidisciplinary team.

The Prognostic Value of Tumor Infiltrating Lymphocytes After Radical Cystectomy for Bladder Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND: We aimed to assess the prognostic value of tumor infiltrating lymphocytes (TILs) in patients with bladder cancer (BC) after radical cystectomy (RC). MATERIALS AND METHODS: We searched Pubmed, Web of Science and Scopus in April 2022 to identify studies assessing the prognostic value of TILs, including a subset of lymphocytes (eg, CD3, CD8, FOXP3), after RC. The endpoints were overall survival and recurrent free survival. Subgroup analyses were performed based on the evaluation method for TILs (ie, CD3, CD8, FOXP3, HE staining). RESULTS: Overall, 9 studies comprising 1413 patients were included in this meta-analysis. The meta-analysis revealed that elevated expressions of TILs were significantly associated with favorable OS (pooled hazard ratio [HR]: 0.65, 95% confidence interval [CI]: 0.51-0.83) and RFS (pooled HR: 0.48, 95% CI: 0.35-0.64). In subgroup analyses, high CD8+ TILs were also associated with favorable OS (HR: 0.51, 95% CI: 0.33-0.80) and RFS (pooled HR: 0.53, 95% CI: 0.36-0.76). Among 3 studies comprising 146 patients, high intratumoral TILs were significantly associated with favorable OS (pooled HR: 0.34, 95% CI: 0.19-0.60). CONCLUSION: TILs are useful prognostic markers in patients treated with RC for BC. Although the prognostic value of TILs is varied, depending on the subset and infiltration site, CD8+ TILs and intratumoral TILs are associated with oncologic outcomes. Further studies are warranted to explicate the predictive value of TILs on the response to perioperative systemic therapy to help clinical decision-making in patients with BC.

Long-term follow-up of intravesical abobotulinumtoxinA (Dysport®) injections in women with idiopathic detrusor overactivity.

Objective: Only a few numbers of studies have been published on the use of abobotulinumtoxinA (Dysport®) in idiopathic detrusor overactivity (IDO). This study reported the long-term follow-up of women with IDO who were treated with intravesical Dysport® injections. Methods: Two hundred and thirty-six patients with IDO who had failed first-line conservative and antimuscarinic therapy received 500-900 units of Dysport® between April 2014 and July 2015. All patients were followed up for 5 years after their initial injection and interviewed on the phone. Results: A total of 236 women with IDO aged from 18 years to 84 years (mean±standard deviation: 49.6±15.9 years) were included in our study. The median follow-up time for patients was 36.5 (range: 10-70) months, and the median recovery time after injection was 18.5 (range: 0-70) months. A total of 83 (35.2%) patients stated that they had subjective improvement of their symptoms whereas 84 (35.6%) patients did not report any improvement in symptoms. The initial International Consultation on Incontinence Questionnaire Overactive Bladder mean score was 6.9 (standard deviation 3.4). There was a positive association between the median recovery time and the components of the International Consultation on Incontinence Questionnaire Overactive Bladder questionnaire. Conclusion: In a sub-population of overactive bladder patients with IDO who have failed first-line therapy, a single intravesical Dysport® injection can resolve patient symptoms completely or reduce the symptoms to an acceptable level that can be controlled with antimuscarinics or re-injection on demands.

Role of clinicopathological variables in predicting recurrence and survival outcomes after surgery for non-metastatic renal cell carcinoma: Systematic review and meta-analysis.

Renal cell carcinoma (RCC) represents 2% of all diagnosed malignancies worldwide, with disease recurrence affecting 20% to 40% of patients. Existing prognostic recurrence models based on clinicopathological features continue to be a subject of controversy. In this meta-analysis, we summarized research findings that explored the correlation between clinicopathological characteristics and post-surgery survival outcomes in non-metastatic RCC patients. Our analysis incorporates 99 publications spanning 140 568 patients. The study's main findings indicate that the following clinicopathological characteristics were associated with unfavorable survival outcomes: T stage, tumor grade, tumor size, lymph node involvement, tumor necrosis, sarcomatoid features, positive surgical margins (PSM), lymphovascular invasion (LVI), early recurrence, constitutional symptoms, poor performance status (PS), low hemoglobin level, high body-mass index (BMI), diabetes mellitus (DM) and hypertension. All of which emerged as predictors for poor recurrence-free survival (RFS) and cancer-specific survival. Clear cell (CC) subtype, urinary collecting system invasion (UCSI), capsular penetration, perinephric fat invasion, renal vein invasion (RVI) and increased C-reactive protein (CRP) were all associated with poor RFS. In contrast, age, sex, tumor laterality, nephrectomy type and approach had no impact on survival outcomes. As part of an additional analysis, we attempted to assess the association between these characteristics and late recurrences (relapses occurring more than 5 years after surgery). Nevertheless, we did not find any prediction capabilities for late disease recurrences among any of the features examined. Our findings highlight the prognostic significance of various clinicopathological characteristics potentially aiding in the identification of high-risk RCC patients and enhancing the development of more precise prediction models.

Efficacy and safety of desmopressin in nocturia and nocturnal polyuria control of neurological patients: A systematic review and meta-analysis.

PURPOSE: Evidence on the efficacy of desmopressin in nocturia in patients with neurological diseases is still very limited except for multiple sclerosis (MS). Our aim was to evaluate the efficacy and safety of desmopressin treatment on nocturia in patients with underlying neurological diseases. METHODS: Studies were identified by electronic search of PubMed, Embase, Cochrane, CINAHL, and Google Scholar databases. Studies were considered if they provided information on the effectiveness and safety of desmopressin (1-desamino-8-d-arginine vasopressin, or DDAVP) in the treatment of nocturia and their participants had acquired neurological pathology. Two researchers independently extracted the articles using specified datasets, such as quality-of-study indicators. Statistical meta-analysis was carried out using Review Manager (RevMan) 5.4 statistical software (Cochrane Collaboration). RESULTS: Of a total of 1042 articles in the initial search, 14 studies were included. Most of the published papers were related to MS (n = 7), two were on spinal cord injury, and other conditions were neural tube defect, myelodysplasia, Parkinson's disease, stroke, and multiple system atrophy. Overall, a total of 200 patients (mostly females) were enrolled. Thirteen studies evaluated the intranasal formulation of desmopressin and one study evaluated oral desmopressin. A significant decrease in nocturia episodes was reported in seven studies evaluating this topic. An increase in the maximum hours of uninterrupted sleep was reported in the three studies in which this outcome was assessed. A significant reduction in the volume of nocturnal incontinence was found in one study. Three studies were eligible to include in the meta-analysis. The results showed that desmopressin compared to placebo, significantly reduced nighttime urination (mean difference: -0.75, 95% CI: -1.10 to -0.41; p < 0.00001). The rate of adverse events ranged from 0% to 68.42%. The critical appraisal results for all trials showed that most of the studies had low or moderate quality. CONCLUSIONS: Our results emphasized desmopressin's safety and efficacy in reducing nocturia episodes, with transient adverse effects on neurological patients. However, the data were achieved from low or medium-quality trials, and further well-designed randomized controlled trials are needed.

Urinary function in female patients after traditional, organ-sparing and nerve-sparing radical cystectomy for bladder cancer: a systematic review and pooled analysis.

OBJECTIVES: To determine and summarize the available data on urinary, sexual, and health-related quality-of-life (HRQOL) outcomes after traditional radical cystectomy (RC), reproductive organ-preserving RC (ROPRC) and nerve-sparing RC (NSRC) for bladder cancer (BCa) in female patients. METHODS: The PubMed, SCOPUS and Web of Science databases were searched to identify studies reporting functional outcomes in female patients undergoing RC and urinary diversion for the treatment of BCa. The outcomes of interest were voiding function (for orthotopic neobladder [ONB]), sexual function and HRQOL. The following independent variables were derived and included in the meta-analysis: pooled rate of daytime and nighttime continence/incontinence, and intermittent self-catheterization (ISC) rates. Analyses were performed separately for traditional, organ- and/or nerve-sparing surgical approaches. RESULTS: Fifty-three studies comprising 2740 female patients (1201 traditional RC and 1539 organ-/nerve-sparing RC, and 264 nerve-sparing-alone RC) were eligible for qualitative synthesis; 44 studies comprising 2418 female patients were included in the quantitative synthesis. In women with ONB diversion, the pooled rates of daytime continence after traditional RC, ROPRC and NSRC were 75.2%, 79.3% and 71.2%, respectively. The pooled rate of nighttime continence after traditional RC was 59.5%; this rate increased to 70.7% and 71.7% in women who underwent ROPRC and NSRC, respectively. The pooled rate of ISC after traditional RC with ONB diversion in female patients was 27.6% and decreased to 20.6% and 16.8% in patients undergoing ROPRC and NSRC, respectively. The use of different definitions and questionnaires in the assessment of postoperative sexual and HRQOL outcomes did not allow a systematic comparison. CONCLUSIONS: Female organ- and nerve-sparing surgical approaches during RC seem to result in improved voiding function. There is a significant need for well-designed studies exploring sexual and HRQOL outcomes to establish evidence-based management strategies to support a shared decision-making process tailored towards patient expectations and satisfaction. Understanding expected functional, sexual and quality-of-life outcomes is necessary to allow individualized pre- and postoperative counselling and care delivery in female patients planned to undergo RC.

Fixed-effect Versus Random-effects Models for Meta-analyses: Fixed-effect Models.

A fixed-effect model considers a common underlying effect size for all the studies included in a meta-analysis. In the face of appreciable between-study heterogeneity, a fixed-effect model is a valuable tool when precision is the priority.

Impact of performance status on efficacy of systemic therapy for prostate cancer: a meta-analysis.

OBJECTIVE: To evaluate the efficacy of systemic therapies in patients with worse performance status (PS) treated for high-risk non-metastatic prostate cancer (PCa), metastatic hormone-sensitive PCa (mHSPC), and non-metastatic/metastatic castration-resistant PCa (nmCRPC/mCRPC), as there is sparse pooled data showing the effect of PS on oncological outcomes in patients with PCa. METHODS: Three databases were queried in June 2022 for randomised controlled trials (RCTs) analysing patients with PCa treated with systemic therapy (i.e., adding androgen receptor signalling inhibitor [ARSI] or docetaxel [DOC] to androgen-deprivation therapy [ADT]). We analysed the oncological outcomes of patients with PCa with worse PS, defined as Eastern Cooperative Oncology Group PS ≥ 1, treated with combination therapies and compared these to patients with good PS. The main outcomes of interest were overall survival (OS), metastasis-free survival (MFS), and progression-free survival. RESULTS: Overall, 25 and 18 RCTs were included for systematic review and meta-analyses/network meta-analyses, respectively. In all clinical settings, combination systemic therapies significantly improved OS in patients with worse PS as well as in those with good PS, while the MFS benefit from ARSI in the nmCRPC setting was more pronounced in patients with good PS than in those with worse PS (P = 0.002). Analysis of treatment ranking in patients with mHSPC revealed that triplet therapy had the highest likelihood of improved OS irrespective of PS; specifically, adding darolutamide to DOC + ADT had the highest likelihood of improved OS in patients with worse PS. Analyses were limited by the small proportion of patients with a PS ≥ 1 (19%-28%) and that the number of PS 2 was rarely reported. CONCLUSIONS: Among RCTs, novel systemic therapies seem to benefit the OS of patients with PCa irrespective of PS. Our findings suggest that worse PS should not discourage treatment intensification across all disease stages.

Role of pelvic drain and timing of urethral catheter removal following RARP: a systematic review and meta-analysis.

OBJECTIVES: To assess the clinical value of routine pelvic drain (PD) placement and early removal of urethral catheter (UC) in patients undergoing robot-assisted radical prostatectomy (RARP), as perioperative management such as the necessity of PD or optimal timing for UC removal remains highly variable. METHODS: Multiple databases were searched for articles published before March 2022 according to the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) statement. Studies were deemed eligible if they investigated the differential rate of postoperative complications between patients with/without routine PD placement and with/without early UC removal, defined as UC removal at 2-4 days after RARP. RESULTS: Overall, eight studies comprising 5112 patients were eligible for the analysis of PD placement, and six studies comprising 2598 patients were eligible for the analysis of UC removal. There were no differences in the rate of any complications (pooled odds ratio [OR] 0.89, 95% confidence interval [CI] 0.78-1.00), severe complications (Clavien-Dindo Grade ≥III; pooled OR 0.95, 95% CI 0.54-1.69), all and/or symptomatic lymphocele (pooled OR 0.82, 95% CI 0.50-1.33; and pooled OR 0.58, 95% CI 0.26-1.29, respectively) between patients with or without routine PD placement. Furthermore, avoiding PD placement decreased the rate of postoperative ileus (pooled OR 0.70, 95% CI 0.51-0.91). Early removal of UC resulted in an increased likelihood of urinary retention (OR 6.21, 95% CI 3.54-10.9) in retrospective, but not in prospective studies. There were no differences in anastomosis leakage and early continence rates between patients with or those without early removal of UC. CONCLUSIONS: There is no benefit for routine PD placement after standard RARP in the published articles. Early removal of UC seems possible with the caveat of the increased risk of urinary retention, while the effect on medium-term continence is still unclear. These data may help guide the standardisation of postoperative procedures by avoiding unnecessary interventions, thereby reducing potential complications and associated costs.

Microbiome in Lower Urinary Tract Symptoms (LUTSs): Mapping the State of the Art with Bibliometric Analysis.

BACKGROUND: The main objective of this study is to provide the first characterization of the current research field of the clinical microbiome in LUTSs. METHODS: First-of-its-kind scientometric insight into the historical development and structural state of the discipline is provided by a field analysis, mapping, and sub-analysis of articles for future research. On 22 December 2022, the entire Scopus database was searched without language or date restrictions. Search terms included "Chronic prostatitis", OR "Interstitial cystitis", OR "Lower urinary tract symptoms", OR "Lower urinary tract dysfunction", OR "Overactive bladder", OR "Incontinence", OR "Urolithiasis", OR "Urothelium", OR "Urine", OR "Urology", OR "urinary disorder", OR "Pathophysiology", OR "Benign prostatic hyperplasia", OR "Benign prostatic enlargement", AND "Microbiota", OR "Microbiome", OR "Urobio-ma", OR "Urobiota; microflora". The author and institutional data were transformed using the analytical tool Biblioshiny (a Shiny app for Bibliometrix), which took into account variations in author spelling as well as institutional naming and subgroups. RESULTS: The specified search strategy was able to locate 529 documents from 267 sources published from 1981 to 2022. The average number of years from publication was 4.59 years. The authors with the most publications were Wolfe AJ and Brubaker I. The top three most collaborative networks were Loyola University Chicago, Loyola University Medical Center, and the University of California San Diego. The most frequently occurring words among the 50 nodes were: human, humans, nonhuman, female, adult, article, microbiology, microflora, microbiota, and controlled study. Frontiers in Cellular and Infection Microbiology and the International Urogynecology Journal, followed by Nature Reviews Urology, were the top three most relevant sources in microbiome research in urology. CONCLUSIONS: One of the most crucial requirements for developing research policies and anticipating the scientific requirements of researchers is paying attention to the evolution of various scientific fields. Understanding research gaps and future needs in microbiome research in urology can be effectively understood by paying attention to the models, maps, and visualizations used in this research, which are the results of systematic analysis of scientific products in the most esteemed scientific journals in the world.

Predictive and Prognostic Role of the Neutrophil-to-Lymphocyte Ratio in Muscle Invasive Bladder Cancer Treated With Neoadjuvant Chemotherapy and Radical Cystectomy.

INTRODUCTION: There is a persistent lack of validated biomarkers that identify patients most likely to benefit from neoadjuvant chemotherapy (NAC) in urothelial carcinoma of the bladder (UCB). Therefore, the purpose of this study was to investigate the predictive and prognostic impact of the pretreatment neutrophil-to-lymphocyte ratio (NLR) in UCB patients treated with NAC and radical cystectomy (RC). PATIENTS AND METHODS: We conducted a retrospective analysis of an international-multicenter database comprising 404 UCB patients staged cT2-4N0-3M0. The cohort was split into low and high NLR using an optimal cutoff value determined by maximizing Youden's index. Logistic and Cox regression analyses were performed with respect to several clinical endpoints. The discriminative ability of the models and the additive discriminative value of NLR was assessed by calculating the area under receiver operating characteristics curves, C-index, and decision curve analysis (DCA). RESULTS: A total of 169 patients (41.8%) had a high NLR, which was associated with a decreased probability of complete response (CR, OR: 0.24 [95% CI, 0.13-0.42], P < .001) and/or partial response (PR, OR: 0.33 [95% CI, 0.21-0.49], P < .001). Adding the NLR to predictive reference models significantly improved their accuracy for the prediction of both CR and PR. A high NLR was associated with poor survival outcomes in the pretreatment setting, however, it didn't meaningfully change the C-index based on the model. CONCLUSION: We confirmed that an elevated NLR is an independent and clinically significant predictor of response to NAC and adverse pathological features in UCB treated with NAC plus RC. The accuracy of this biomarker in the age of immunotherapy warrants further evaluation.

Impact of Performance Status on Oncologic Outcomes in Patients with Advanced Urothelial Carcinoma Treated with Immune Checkpoint Inhibitor: A Systematic Review and Meta-analysis.

CONTEXT: Immune checkpoint inhibitors (ICIs) are widely used in the management of patients with advanced urothelial carcinoma (aUC). However, its performance in aUC patients with poor performance status (PS) remains unknown. OBJECTIVE: We aimed to assess the impact of patients' performance status on the oncologic outcomes in patients with aUC treated with ICIs. EVIDENCE ACQUISITION: We searched PubMed, Web of Science, and Scopus from inception until July 2022 to identify studies assessing the association between the Eastern Cooperative Oncology Group (ECOG) PS and the oncologic outcomes in patients with aUC treated with ICIs in randomised (RCTs) and nonrandomised (NRCTs) control studies according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. The outcomes of our interests were overall survival (OS), cancer-specific survival (CSS), progression-free survival (PFS), and objective response rate (ORR). EVIDENCE SYNTHESIS: Overall, six RCTs comprising 5428 patients and 32 NRCTs comprising 6069 patients were included. The meta-analysis of the RCTs revealed that patients with ECOG PS = 0 and PS ≥1 had a trend towards better OS with ICIs compared with those treated with chemotherapy (pooled hazard ratio [HR]: 0.86, 95% confidence interval [CI]: 0.71-1.04, and HR: 0.74, 95% CI: 0.53-1.03, respectively). There was no significant difference in terms of response to ICIs between patients with poor and good PS (I2 = 0%, p = 0.46). The meta-analysis of the NRCTs revealed that patients with PS ≥2 had significantly worse OS than those with PS <2 (pooled HR: 2.52, 95% CI: 2.00-3.17), as well as worse CSS (pooled HR: 3.35, 95% CI: 1.90-5.91), PFS (pooled HR: 2.89, 95% CI: 1.67-5.01), and ORR (pooled odds ratio: 0.47, 95% CI: 0.27-0.82). Similarly, patients with PS ≥1 had significantly worse oncologic outcomes than those with PS = 0. CONCLUSIONS: In the NRCTs, poor PS was correlated with worse oncologic outcomes in aUC patients treated with ICIs. In the RCTs, ICIs performed better than chemotherapy across all PS categories. These findings should be interpreted with caution due to the high heterogeneity across the studies and patient populations. More RCTs including poor PS are needed to assess the impact of PS on ICI therapy outcomes. PATIENT SUMMARY: Immune therapy for patients with urothelial carcinoma should not be restricted on the grounds of performance status. However, patients with poor performance status should be considered for other factors such as life expectancy and comorbidities.

A Systematic Review and Meta-analysis of Chemoablation for Non-muscle-invasive Bladder Cancer.

CONTEXT: The ablative effect of intravesical therapy is known for decades. However, the clinical feasibility and efficacy of chemoablation for non-muscle-invasive bladder cancer (NMIBC) have not become accepted. OBJECTIVE: To assess the treatment outcomes of chemoablation for NMIBC and to compare its safety with that of the standard treatment, transurethral resection of bladder tumors (TURBT) followed by intravesical therapy. EVIDENCE ACQUISITION: Multiple databases were queried in July 2022 for studies investigating the complete response (CR) rates and adverse events in NMIBC patients treated with chemoablation using mitomycin C (MMC), gemcitabine, epirubicin, or bacillus Calmette-Guérin. EVIDENCE SYNTHESIS: Overall, 23 studies comprising 1199 patients were eligible for this meta-analysis. Among these studies, 20 assessed the efficacy of chemoablation and three compared the treatment outcomes of MMC chemoablation versus standard treatment. Among patients treated with weekly administration of any agent, the pooled CR rates at initial assessment were 50.9% (95% confidence interval [CI]: 45.9-55.9) for the marker lesion and 47.5% (95% CI: 36.5-58.7) for well-selected NMIBC (ie, small tumors and/or a small number of tumors). Novel regimens for chemoablation such as MMC-gel (70.6%, 95% CI: 60.1-79.3) and an intensive MMC regimen (64.7%, 95% CI: 56.2-72.3) provided better CR rates in well-selected NMIBC patients. Comparable CR rates were noted irrespective of tumor multiplicity, whereas tumor size <5 mm was associated with a higher CR rate than tumor size ≥5 mm (odds ratio: 0.36, 95% CI: 0.17-0.79). The novel intensive MMC regimen resulted in lower rates of dysuria and urinary frequency than standard treatment. CONCLUSIONS: Despite the lack of long-term outcomes, chemoablation appears to be a promising treatment option for well-selected NMIBC patients and can potentially help avoid unnecessary TURBT, specifically in some elderly patients with intermediate-risk NMIBC. Further well-designed studies with larger cohorts are necessary to address the differential tolerability and long-term anticancer efficacy of this resurging approach. PATIENT SUMMARY: Bladder instillation therapy has a potential ablative effect for well-selected non-muscle-invasive bladder cancer. This can lead to the omission of an unnecessary surgical treatment.

Oncological impact of cystoscopic findings in non-muscle-invasive bladder cancer: a meta-analysis.

OBJECTIVE: To assess the association between cystoscopic findings and oncological outcomes in patients with non-muscle-invasive bladder cancer (NMIBC) given that the oncological impact of quantity and quality assessment of tumours with cystoscopy has not been well verified. METHODS: Multiple databases were queried in May 2022 for studies investigating the association of oncological outcomes, such as recurrence-free (RFS), progression-free (PFS), and cancer-specific survival (CSS), with cystoscopic findings, including multiplicity, size, and gross appearance of tumours in patients with NMIBC. RESULTS: Overall, 73 studies comprising 28 139 patients were eligible for the meta-analysis. Tumour multiplicity was associated with worse RFS (pooled hazard ratio [HR] 1.61, 95% confidence interval [CI] 1.48-1.74) and PFS (pooled HR 1.44, 95% CI 1.18-1.76) in NMIBC patients (including both Ta and T1). Tumour size (≥3 cm) was associated with worse RFS (pooled HR 1.97, 95% CI 1.69-2.30) and PFS (pooled HR 1.81, 95% CI 1.52-2.15) in NMIBC patients. In patients with T1 bladder cancer (BCa), tumour multiplicity and size (≥3 cm) were also associated with worse RFS, PFS and CSS. By contrast, among patients treated with bacillus Calmette-Guérin (BCG), tumour multiplicity was not associated with worse RFS, and tumour size (≥3 cm) was not associated with worse PFS. Sessile tumours were associated with worse RFS (pooled HR 2.14, 95% CI 1.52-3.01) and PFS (pooled HR 2.17, 95% CI 1.42-3.32) compared to pedunculated tumours. Compared to papillary tumours, solid tumours were associated with worse RFS (pooled HR 1.84, 95% CI 1.25-2.72) and PFS (pooled HR 3.06, 95% CI 2.31-4.07) in NMIBC patients, and CSS in T1 BCa patients (pooled HR 2.32, 95% CI 1.63-3.30). CONCLUSIONS: Cystoscopic findings, including tumour multiplicity, size, and gross appearance, strongly predict oncological outcomes in NMIBC patients. Cystoscopic visual features can help in the decision-making process regarding the timeliness and extent of tumour resection as well as future management such as intravesical therapy.

Perspectives on the future of urothelial carcinoma therapy: chemotherapy and beyond.

INTRODUCTION: Despite recent developments in the landscape of urothelial carcinoma (UC) treatment, platinum combination chemotherapy still remains a milestone. Recently immunotherapeutic agents have gained ever-growing attractivity, particularly in the metastatic setting. Novel chemotherapeutic strategies and agents, such as antibody-drug conjugates (ADCs), and powerful combination regimens have been developed to overcome the resistance of most UC to current therapies. AREAS COVERED: Herein, we review the current standard-of-care chemotherapy, the development of ADCs, the rationale for combining therapy regimens with chemotherapy in current trials, and future directions in UC management. EXPERT OPINION: Immunotherapy has prompted a revolution in the treatment paradigm of UC. However, only a few patients experience a long-term response when treated with single-agent immunotherapies. Combination treatments are necessary to bypass resistance mechanisms and broaden the clinical utility of current options. Current evidence supports the intensification of standard-of-care chemotherapy with maintenance immunotherapy. However, the optimal sequence, combination, and duration must be determined to achieve individual longevity with acceptable health-related quality of life. In that regard, ADCs appear as a promising alternative for single and combination strategies in UC, as they specifically target the tumor cells, thereby, theoretically improving treatment efficacy and avoiding extensive off-target toxicities.

Impact of sex on outcomes after surgery for non-muscle-invasive and muscle-invasive bladder urothelial carcinoma: a systematic review and meta-analysis.

PURPOSE: To assess the prognostic value of sex for non-muscle-invasive/muscle-invasive bladder urothelial carcinoma (NMIBC/MIBC) treated with radical surgery. METHODS: The PubMed, Web of Science, and Scopus databases were searched in November 2021 according to the Preferred Reporting Items for Systematic Review and Meta-analysis statement. Studies were deemed eligible if they involved the comparison of the overall, cancer-specific, progression, and recurrence-free survival of patients with NMIBC/MIBC. Formal sex-stratified meta-analyses of these outcomes were performed. RESULTS: Thirty-one studies, which included 32,525 patients with NMIBC, and 63 studies, which included 85,132 patients with MIBC, were eligible for review and meta-analysis. Female sex was associated with worse cancer-specific survival (pooled hazard ratio [HR], 1.21; 95% confidence interval [CI], 1.11-1.31) and overall survival (pooled HR, 1.02; 95% CI, 1.00-1.05) in patients with MIBC. In contrast, however, sex was not associated with cancer-specific survival (pooled HR, 1.01; 95% CI, 0.70-1.46), progression-free survival (pooled HR, 1.04; 95% CI, 0.88-1.24), and recurrence-free survival (pooled HR, 1.06; 95% CI, 0.98-1.16) in patients with NMIBC. CONCLUSIONS: Sex is associated with an increased risk of worse survival outcomes in patients with MIBC but not in those with NMIBC. Given the genetic and social differences between sexes, sex may represent a key factor in the clinical decision-making process.

Sequencing impact and prognostic factors in metastatic castration-resistant prostate cancer patients treated with cabazitaxel: A systematic review and meta-analysis.

BACKGROUND: Cabazitaxel is an effective treatment of post-docetaxel metastatic castration-resistant prostate cancer (mCRPC). We aimed to assess the sequencing impact and identify prognostic factors of oncologic outcomes in mCRPC patients treated with cabazitaxel. METHODS: PUBMED, Web of Science, and Scopus databases were searched for articles published before January 2022 according to the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analyses) statement. Studies were deemed eligible if they investigated pretreatment clinical or hematological prognostic factors of overall survival (OS) in mCRPC patients with progression after docetaxel treated with available treatments including cabazitaxel. RESULTS: Overall, 22 studies were eligible for the meta-analysis. In mCRPC patients treated with docetaxel, subsequent treatment with cabazitaxel was associated with better OS compared to that without cabazitaxel (pooled hazard ratio [HR]: 0.70, 95% confidence interval [CI]: 0.56-0.89). Among the patients treated with cabazitaxel, several pretreatment clinical features and hematologic biomarkers were associated with worse OS as follows: poor performance status (PS) (pooled HR: 1.92, 95% CI: 1.33-2.77), presence of visceral metastasis (pooled HR: 2.13, 95% CI: 1.62-2.81), symptomatic disease (pooled HR: 1.47, 95% CI: 1.25-1.73), high PSA (pooled HR: 1.76, 95% CI: 1.27-2.44), high alkaline phosphatase (ALP) (pooled HR: 1.45, 95% CI: 1.28-1.65), high lactate dehydrogenase (LDH) (pooled HR: 1.54, 95% CI: 1.00-2.38), high c-reactive protein (CRP) (pooled HR: 4.40, 95% CI: 1.52-12.72), low albumin (pooled HR:1.09, 95% CI: 1.05-1.12) and low hemoglobin (pooled HR:1.55, 95% CI: 1.20-1.99). CONCLUSIONS: Sequential therapy with cabazitaxel significantly improves OS in post-docetaxel mCRPC patients. In mCRPC patients treated with cabazitaxel, patients with poor PS, visceral metastasis, and symptomatic disease were associated with worse OS. Further, pretreatment high PSA, ALP, LDH or CRP as well as low hemoglobin or albumin, were blood-based prognostic factors for OS. These findings might help guide the clinical decision-making for the use of cabazitaxel and prognostication of its OS benefit.

Iatrogenic ureteric injury during abdominal or pelvic surgery: a meta-analysis.

OBJECTIVE: To assess the incidence of ureteric injuries, clinical value of prophylactic ureteric stenting and impact of intra- or postoperative detection of ureteric injuries in patients treated with gynaecological or colorectal surgery. METHODS: Multiple databases were searched for articles published before September 2021 according to the Preferred Reporting Items for Systematic Review and Meta-Analyses statement. Studies were deemed eligible if they evaluated the differences in the rate of ureteric injuries between laparoscopic and open surgery, prophylactic ureteric stenting or not, and those of final treatment success between intra- and postoperative detection in patients who underwent gynaecological or colorectal surgery. RESULTS: Overall, 46 studies were eligible for this meta-analysis. Compared to open surgery, laparoscopic hysterectomy was associated with a higher incidence of ureteric injuries (pooled odds ratio [OR] 2.12, 95% confidence interval [CI] 1.71-2.62), but there was no statistically significant difference in colectomy (pooled OR 0.89, 95% CI 0.77-1.03). Prophylactic ureteric stenting was associated with a lower incidence of ureteric injuries during gynaecological surgery (pooled OR 0.61, 95% CI 0.39-0.96). The number needed to perform ureteric stenting to prevent one ureteric injury was 224 in gynaecological surgery. On the other hand, prophylactic ureteric stenting did not reduce the risk of ureteric injuries during colorectal surgery. Intraoperative detection of a ureteric injury was associated with a lower rate of complication management failure compared to postoperative detection (pooled OR 0.22, 95% CI 0.12-0.41). CONCLUSIONS: Laparoscopic hysterectomy seems to be associated with a higher rate of ureteric injuries compared to an open approach. Prophylactic ureteric stenting seems to reduce this risk during gynaecological surgery. Intraoperative detection of a ureteric injury during abdominal/pelvic surgery improves outcomes, suggesting the need for awareness and proactive problem identification. Further well-designed studies assessing the candidates who are more likely to benefit from prophylactic ureteric stenting including cost analysis are needed.