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.

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.

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.

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.

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.

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.

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.

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.

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.

Impact of preoperative plasma levels of interleukin 6 and interleukin 6 soluble receptor on disease outcomes after radical cystectomy for bladder cancer.

BACKGROUND: Preoperative plasma levels of Interleukin 6 (IL6) and its soluble receptor (IL6sR) have previously been associated with oncologic outcomes in urothelial carcinoma of the bladder (UCB); however, external validation in patients treated with radical cystectomy (RC) for UCB is missing. PATIENTS/METHODS: We prospectively collected preoperative plasma from 1,036 consecutive patients at two institutes. These plasma specimens were assessed for levels of IL6 and IL6sR. Logistic and Cox regression analyses were used to assess the correlation of plasma levels with pathologic and survival outcomes. The additional clinical net benefits of preoperative IL6 and IL6sR were evaluated using decision curve analysis (DCA). RESULTS: Median IL6 and IL6sR plasma levels were significantly higher in patients with adverse pathologic features. Elevated biomarker levels were independently associated with an increased risk for lymph node metastasis and ≥ pT3 disease. Both biomarkers were independently associated with recurrence-free survival (RFS), cancer-specific survival (CSS) and overall survival (OS). The addition to, respectively, fitted pre- and postoperative prognostic models improved the predictive accuracy for lymph node metastasis, ≥ pT3 disease, RFS and CSS on DCA. INTERPRETATION: We confirmed that elevated preoperative plasma levels of IL6 and IL6sR levels are associated with worse oncological disease survival in patients treated with RC for UCB in a large multicenter study. Both biomarkers hold potential in identifying patients with adverse pathological features that may benefit from intensified/multimodal therapy and warrant inclusion into predictive/prognostic models. They demonstrated the ability to improve the discriminatory power of such models and thus guide clinical decision making.