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European Urology Focus Mar 2022Patients with intermediate-risk non-muscle-invasive bladder cancer (NMIBC) may pose a clinical dilemma without an agreed evidence-based decision tree for personalized... (Meta-Analysis)
Meta-Analysis Review
CONTEXT
Patients with intermediate-risk non-muscle-invasive bladder cancer (NMIBC) may pose a clinical dilemma without an agreed evidence-based decision tree for personalized treatment.
OBJECTIVE
To perform a systematic review and network meta-analysis (NMA) to summarize available evidence on the oncologic outcomes of intravesical therapy in patients with intermediate-risk NMIBC.
EVIDENCE ACQUISITION
The MEDLINE, EMBASE, and ClinicalTrials.gov databases were searched in October 2020 according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. Studies were deemed eligible if they reported on oncologic outcomes in patients with intermediate-risk NMIBC treated with transurethral resection of bladder tumor with and without intravesical chemotherapy or bacillus Calmette-Guérin (BCG) immunotherapy.
EVIDENCE SYNTHESIS
Twelve studies were included in a qualitative synthesis (systematic review); three were deemed eligible for a quantitative synthesis (NMA). An NMA of five different regimens was conducted for the association of treatment with the 5-yr recurrence risk. Chemotherapy with maintenance was associated with a lower likelihood of 5-yr recurrence than chemotherapy without maintenance (odds ratio [OR] 0.51, 95% credible interval [CI] 0.26-1.03). Immunotherapy, regardless of whether a full- or reduced-dose regimen, was not associated with a significantly lower likelihood of 5-yr recurrence when compared with chemotherapy without maintenance (OR 0.90, 95% CI 0.39-2.11 vs OR 0.93, 95% CI 0.40-2.19). Analysis of the treatment ranking revealed that chemotherapy with maintenance had the lowest 5-yr recurrence risk (P score 0.9666).
CONCLUSIONS
Our analysis indicates that chemotherapy with a maintenance regimen confers a superior oncologic benefit in terms of 5-yr recurrence risk compared to chemotherapy without maintenance in patients with intermediate-risk NMIBC. Regardless of the dose regimen, immunotherapy with BCG does not appear to be superior to chemotherapy in patients with intermediate-risk NMIBC in term of disease recurrence. However, owing to the lack of comparative studies, there is an unmet need for well-designed, large-scale trials to validate our findings and generate robust evidence on disease recurrence and progression.
PATIENT SUMMARY
A maintenance schedule of chemotherapy reduces the rate of long-term recurrence of bladder cancer that has not invaded the bladder muscle. Chemotherapy inserted directly into the bladder and immunotherapy without maintenance schedules seem to have limited benefit in preventing cancer recurrence.
Topics: Administration, Intravesical; BCG Vaccine; Humans; Neoplasm Recurrence, Local; Network Meta-Analysis; Urinary Bladder Neoplasms
PubMed: 33762203
DOI: 10.1016/j.euf.2021.03.016 -
Indian Journal of Urology : IJU :... 2021The emergence of urinary biomarkers for bladder cancer diagnosis could provide a reliable and less invasive diagnostic method. It could be also used as an adjuvant to... (Review)
Review
INTRODUCTION
The emergence of urinary biomarkers for bladder cancer diagnosis could provide a reliable and less invasive diagnostic method. It could be also used as an adjuvant to the current gold standards of cytology and cystoscopy to improve diagnostic accuracy and decrease the percentage of false positives.
METHODS
We searched PubMed, SCOPUS, and Web of Science up to March 18, 2020. We selected four studies that assessed the diagnostic accuracy of urinary apolipoprotein A1 (ApoA-1) in detecting bladder cancer and met the inclusion and exclusion criteria. Two authors independently extracted the data and performed quality assessment of the studies.
RESULTS
Four studies with 771 participants were selected; 417 were bladder cancer patients and 354 were controls. Bladder cancer was either transitional cell carcinoma or squamous cell carcinoma, the stages varied between Ta to T3, and the grades varied between G1 and G3. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were 90.7%, 90%, 9.478, 0.1, and 99.424, respectively. Summary receiver operating characteristic curve showed an area under the curve of 0.9544 and Q* index of 0.8965.
CONCLUSIONS
ApoA-1 showed high sensitivity and specificity, so it could be a useful biomarker in diagnosis of bladder cancer.
PubMed: 34465950
DOI: 10.4103/iju.IJU_69_21 -
International Braz J Urol : Official... 2022There is an ongoing need to identify various pathological factors that can predict various survival parameters in patients with upper tract urothelial carcinoma (UTUC).... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
There is an ongoing need to identify various pathological factors that can predict various survival parameters in patients with upper tract urothelial carcinoma (UTUC). With this review, we aim to scrutinize the impact of several pathological factors on recurrence free survival (RFS), cancer-specific survival (CSS) and overall survival (OS) in patients with UTUC.
MATERIALS AND METHODS
Systematic electronic literature search of various databases was conducted for this review. Studies providing multivariate hazard ratios (HR) for various pathological factors such as tumor margin, necrosis, stage, grade, location, architecture, lymph node status, lymphovascular invasion (LVI), carcinoma in situ (CIS), multifocality and variant histology as predictor of survival parameters were included and pooled analysis of HR was performed.
RESULTS
In this review, 63 studies with 35.714 patients were included. For RFS, all except tumor location (HR 0.94, p=0.60) and necrosis (HR 1.00, p=0.98) were associated with worst survival. All the pathological variables except tumor location (HR 0.95, p=0.66) were associated with worst CSS. For OS, only presence of CIS (HR 1.03, p=0.73) and tumor location (HR 1.05, p=0.74) were not predictor of survival.
CONCLUSIONS
We noted tumor grade, stage, presence of LVI, lymph node metastasis, hydronephrosis, variant histology, sessile architecture, margin positivity and multifocality were associated with poor RFS, CSS and OS. Presence of CIS was associated with poor RFS and CSS but not OS. Tumor necrosis was associated with worst CSS and OS but not RFS. Tumor location was not a predictor of any of the survival parameters.
Topics: Carcinoma, Transitional Cell; Humans; Prognosis; Retrospective Studies; Ureteral Neoplasms; Urinary Bladder Neoplasms; Urologic Neoplasms
PubMed: 34003609
DOI: 10.1590/S1677-5538.IBJU.2020.1032 -
International Journal of Molecular... Jun 2023MicroRNAs (miRNAs) are emerging as biomarkers for the detection and prognosis of cancers due to their inherent stability and resilience. To summarize the evidence... (Review)
Review
MicroRNAs (miRNAs) are emerging as biomarkers for the detection and prognosis of cancers due to their inherent stability and resilience. To summarize the evidence regarding the role of urinary miRNAs (umiRNAs) in the detection, prognosis, and therapy of genitourinary cancers, we performed a systematic review of the most important scientific databases using the following keywords: (urinary miRNA) AND (prostate cancer); (urinary miRNA) AND (bladder cancer); (urinary miRNA) AND (renal cancer); (urinary miRNA) AND (testicular cancer); (urinary miRNA) AND (urothelial cancer). Of all, 1364 articles were screened. Only original studies in the English language on human specimens were considered for inclusion in our systematic review. Thus, a convenient sample of 60 original articles was identified. UmiRNAs are up- or downregulated in prostate cancer and may serve as potential non-invasive molecular biomarkers. Several umiRNAs have been identified as diagnostic biomarkers of urothelial carcinoma and bladder cancer (BC), allowing us to discriminate malignant from nonmalignant forms of hematuria. UmiRNAs could serve as therapeutic targets or recurrence markers of non-muscle-invasive BC and could predict the aggressivity and prognosis of muscle-invasive BC. In renal cell carcinoma, miRNAs have been identified as predictors of tumor detection, aggressiveness, and progression to metastasis. UmiRNAs could play an important role in the diagnosis, prognosis, and therapy of urological cancers.
Topics: Male; Humans; MicroRNAs; Testicular Neoplasms; Urinary Bladder Neoplasms; Carcinoma, Transitional Cell; Urologic Neoplasms; Kidney Neoplasms; Carcinoma, Renal Cell; Prostatic Neoplasms; Biomarkers, Tumor
PubMed: 37446024
DOI: 10.3390/ijms241310846 -
European Urology Focus Mar 2023We systematically reviewed the literature and summarized oncologic and safety outcomes for endoscopic management (EM) compared to radical nephroureterectomy (RNU) for... (Meta-Analysis)
Meta-Analysis Review
Oncologic and Safety Outcomes for Endoscopic Surgery Versus Radical Nephroureterectomy for Upper Tract Urothelial Carcinoma: An Updated Systematic Review and Meta-analysis.
We systematically reviewed the literature and summarized oncologic and safety outcomes for endoscopic management (EM) compared to radical nephroureterectomy (RNU) for patients with upper tract urothelial carcinoma (UTUC). Studies comparing oncologic and/or safety results for EM versus RNU in patients with UTUC were included in our review. Overall, 13 studies met the criteria, and five studies were included in a meta-analysis using adjusted hazard ratios (HRs) for overall survival (OS), cancer-specific survival (CSS), and bladder recurrence-free survival (BRFS). EM was associated similar OS (HR 1.27, 95% confidence interval [CI] 0.75-2.16), CSS (HR 1.37, 95% CI 0.99-1.91), and BRFS (HR 0.98, 95% CI 0.61-1.55) to RNU, while 28-85% of patients treated with EM experienced upper tract recurrence across the studies. EM required more interventions with a higher cumulative risk of complications and lower likelihood of renal preservation. In summary, EM for low-grade UTUC had comparable survival outcomes to RNU at the cost of higher local recurrence rates resulting in a need for long-term rigorous surveillance and repeated interventions. PATIENT SUMMARY: For selected cases of cancer in the upper urinary tract, surgical treatment via a telescope inserted through the urethra or the skin (endoscope) results in cancer control outcomes that are comparable to those after removal of the kidney and ureter. However, because of its higher rate of local recurrence, this approach requires repeated endoscopic treatment sessions. Patients should be well informed about these issues to help in shared decision-making.
Topics: Humans; Nephroureterectomy; Urinary Bladder Neoplasms; Carcinoma, Transitional Cell; Ureter; Ureteroscopy
PubMed: 36463089
DOI: 10.1016/j.euf.2022.11.016 -
World Journal of Urology Jul 2023To analyze and summarize the efficacy of immune checkpoint inhibitor (ICI) alone or in combination therapy for renal cell carcinoma (RCC) and urothelial carcinoma (UC)... (Meta-Analysis)
Meta-Analysis
PURPOSE
To analyze and summarize the efficacy of immune checkpoint inhibitor (ICI) alone or in combination therapy for renal cell carcinoma (RCC) and urothelial carcinoma (UC) stratified by sex.
METHODS
Three databases were queried in October 2022 for randomized controlled trials (RCTs) analyzing RCC and UC patients treated with ICIs. We analyzed the association between sex and the efficacy of ICIs in RCC and UC patients across several clinical settings. The outcomes of interest were overall survival (OS) and progression-free survival for the metastatic setting and disease-free survival (DFS) for the adjuvant setting.
RESULTS
Overall, 16 RCTs were included for meta-analyses and network meta-analyses. In the first-line treatment of metastatic RCC (mRCC) and UC (mUC) patients, ICI-based combination therapies significantly improved OS compared to the current standard of care, regardless of sex. Adjuvant ICI monotherapy reduced the risk of disease recurrence in female patients with locally advanced RCC (pooled hazard ratio [HR]: 0.71, 95% confidence interval [CI] 0.55-0.93) but not in male patients, and, conversely, in male patients with muscle-invasive UC (pooled HR: 0.80, 95%CI 0.68-0.94) but not in female patients. Treatment ranking analyses in the first-line treatment of mRCC and mUC showed different results between sexes. Of note, regarding adjuvant treatment for RCC, pembrolizumab (99%) had the highest likelihood of improved DFS in males, whereas atezolizumab (84%) in females.
CONCLUSIONS
OS benefit of first-line ICI-based combination therapy was seen in mRCC and mUC patients regardless of sex. Sex-based recommendations for ICI-based regimens according to the clinical setting may help guide clinical decision-making.
Topics: Female; Male; Humans; Immune Checkpoint Inhibitors; Carcinoma, Renal Cell; Neoplasm Recurrence, Local; Carcinoma, Transitional Cell; Urinary Bladder Neoplasms; Kidney; Adjuvants, Immunologic; Kidney Neoplasms
PubMed: 37209143
DOI: 10.1007/s00345-023-04412-0 -
Frontiers in Endocrinology 2021Urinary bladder carcinoma is common in developed settings, and prognosis may be impacted by lifestyle factors such as excess body weight and diabetes mellitus. The... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Urinary bladder carcinoma is common in developed settings, and prognosis may be impacted by lifestyle factors such as excess body weight and diabetes mellitus. The present meta-analysis aimed to systematically collate and analyze evidence on the impact of diabetes and excess BMI on bladder cancer outcomes.
METHODS
PubMed, Scopus, and Google Scholar databases were screened for relevant studies that examined the association between bladder cancer outcomes and diabetes and/or excess body weight. The primary outcomes for this study were mortality (both all-cause and cancer-specific), risk of cancer progression, and recurrence. Strength of association was presented in the form of pooled adjusted hazard ratios (HR). Statistical analysis was performed using STATA version 16.0.
RESULTS
Twenty-five articles met inclusion criteria. Nine of these examined diabetes mellitus while 16 studied body mass index. All studies were retrospective. Diabetic patients had significantly higher risk for all-cause mortality (HR 1.24, 95% CI: 1.07, 1.44, n=3), cancer specific mortality (HR 1.67, 95% CI: 1.29, 2.16, n=7), disease progression (HR 1.54, 95% CI: 1.15, 2.06, n=8), and recurrence (HR 1.40, 95% CI: 1.32, 1.48, n=8) compared to non-diabetics. No statistically significant risk change for all-cause mortality, cancer specific mortality, disease progression, and recurrence was found for overweight patients. However, obese individuals were at higher risk for disease progression (HR 1.88, 95% CI: 1.41, 2.50, n=3) and recurrence (HR 1.60, 95% CI: 1.06, 2.40, n=7) compared to normal BMI patients.
CONCLUSIONS
These findings suggest that diabetes and excess body weight negatively influences bladder cancer prognosis and outcome. The increased risk of mortality due to diabetes was similar to that in the general population. Since retrospective studies are potentially susceptible to bias, future prospective studies on this subject are required.
Topics: Animals; Diabetes Mellitus; Disease Progression; Humans; Obesity; Urinary Bladder Neoplasms
PubMed: 34690923
DOI: 10.3389/fendo.2021.699732 -
European Urology Oncology Nov 2023The optimal therapeutic agent with respect to metastatic sites is unclear in advanced urothelial carcinoma (UC). (Review)
Review
CONTEXT
The optimal therapeutic agent with respect to metastatic sites is unclear in advanced urothelial carcinoma (UC).
OBJECTIVE
To investigate the metastatic organotropism differential treatment response in patients with advanced or metastatic UC.
EVIDENCE ACQUISITION
A systematic search and network meta-analysis (NMA) was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. The primary endpoints of interest were the objective response rate, overall survival (OS), and progression-free survival with respect to different metastatic sites.
EVIDENCE SYNTHESIS
Twenty-six trials comprising 9082 patients met our eligibility criteria, and a formal NMA was conducted. Durvalumab plus tremelimumab as first-line systemic therapy was significantly associated with better OS than chemotherapy in visceral metastasis (hazard ratio [HR] 0.81, 95% confidence interval [CI] 0.67-0.98). Pembrolizumab as second-line systemic therapy was significantly associated with better OS than chemotherapy in patients with visceral metastasis (HR 0.75, 95% CI 0.60-0.95). Atezolizumab as second-line systemic therapy was significantly associated with better OS than chemotherapy in patients with liver metastasis (in the population of >5% of tumor-infiltrating immune cells) and lymph node metastasis (HR 0.51, 95% CI 0.28-0.96, and HR 0.59, 95% CI 0.37-0.96, respectively).
CONCLUSIONS
Administration of immune-oncology treatments with respect to metastatic sites in patients with advanced or metastatic UC might have a positive impact on survival outcomes in both the first- and the second-line setting. Nevertheless, further investigations focusing on metastatic organotropism differential response with reliable oncological outcomes are needed to identify the optimal management strategy for these patients.
PATIENT SUMMARY
Although the supporting evidence for oncological benefits of therapeutic systemic agents with respect to metastatic sites is not yet strong enough to provide a recommendation in advanced or metastatic urothelial carcinoma, clinicians may take into account tumor organotropism only in discussion with the patient fully informed on the optimal treatment decision to be taken.
PubMed: 37980251
DOI: 10.1016/j.euo.2023.11.001 -
European Urology Open Science Sep 2021White light (WL) cystoscopy and transurethral resection of bladder tumour (TURBT) comprise the current gold standard technique for detecting and grading bladder cancer.... (Review)
Review
CONTEXT
White light (WL) cystoscopy and transurethral resection of bladder tumour (TURBT) comprise the current gold standard technique for detecting and grading bladder cancer. However, with WL cystoscopy, recurrence following initial TURBT is high, and identification of smaller tumours and carcinoma in situ is poor. Photodynamic diagnosis (PDD) has been developed to improve the detection of bladder.
OBJECTIVE
To assess the effect of PDD-guided TURBT compared with WL on recurrence rates (RRs) in non-muscle-invasive bladder cancer (NMIBC).
EVIDENCE ACQUISITION
A systematic review of the literature from inception to April 2020 using Medline, EMBASE, and CENTRAL was undertaken. Randomised control trials comparing TURBT undertaken with PDD to WL that reported RRs of at least 12 mo were included in the analysis. The primary outcomes were RRs at 12 and 24 mo. The secondary outcomes were reported adverse effects. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to assess the certainty of the evidence.
EVIDENCE SYNTHESIS
Twelve randomised controlled trials (2288 patients) were included for the meta-analysis. PDD was found to reduce RRs at 12 mo (RR 0.73, confidence interval [CI] 0.60-0.88) and 24 mo (RR 0.75, CI 0.62-0.91). There was an increased risk of recurrence for patients undergoing WL at 12 mo (hazard ratio [HR] 1.14, CI 1.05-1.23) and 24 mo (HR 1.25, CI 1.15-1.35). Two studies reported recurrence data at 60 mo showing statistically significant outcomes in favour of PDD: one showed lower RRs for PDD (49% PDD vs 68% WL), whilst the other showed increased recurrence-free survival (68.2% PDD vs 57.3% WL). Adverse effects appeared to be minimal, though poorly reported. A GRADE analysis showed the evidence to be of moderate certainty overall.
CONCLUSIONS
This systematic review found that PDD reduced RRs and improved recurrence-free survival compared with WL in NMIBC over at least 2-yr follow-up. These effects may persist up to 5 yr. Further research in a pragmatic study looking at longer-term outcomes beyond 24 mo will help guide recommendations on clinical adoption.
PATIENT SUMMARY
This review suggests that photodynamic diagnosis, compared with white light cystoscopy, improves recurrence-free survival in non-muscle-invasive bladder cancer over at least 2 yr of follow-up. However, confirmatory pragmatic studies with longer-term outcomes are required for its clinical adoption.
PubMed: 34467237
DOI: 10.1016/j.euros.2021.06.011 -
International Journal of Molecular... Nov 2014Epithelial-to-mesenchymal transition (EMT) facilitates tumor metastasis. Twist is a basic helix-loop-helix protein that modulates many target genes through... (Meta-Analysis)
Meta-Analysis Review
Epithelial-to-mesenchymal transition (EMT) facilitates tumor metastasis. Twist is a basic helix-loop-helix protein that modulates many target genes through E-box-responsive elements. There are two twist-like proteins, Twist-1 and Twist-2, sharing high structural homology in mammals. Twist-1 was found to be a key factor in the promotion of metastasis of cancer cells, and is known to induce EMT. Twist-1 participation in carcinoma progression and metastasis has been reported in a variety of tumors. However, controversy exists concerning the correlation between Twist-1 and prognostic value with respect to carcinoma. A systematic review and meta-analysis were performed to determine whether the expression of Twist-1 was associated with the prognosis of carcinoma patients. This analysis included 17 studies: four studies evaluated lung cancer, three evaluated head and neck cancer, two evaluated breast cancer, two evaluated esophageal cancer, two evaluated liver cancer and one each evaluated osteosarcoma, bladder, cervical and ovarian cancer. A total of 2006 patients were enrolled in these studies, and the median trial sample size was 118 patients. Twist-1 expression was associated with worse overall survival (OS) at both 3 years (hazard ratio "HR" for death = 2.13, 95% CI = 1.86 to 2.45, p < 0.001) and 5 years (HR for death = 2.01, 95% CI = 1.76 to 2.29, p < 0.001). Expression of Twist-1 is associated with worse survival in carcinoma.
Topics: Gene Expression Regulation, Neoplastic; Genetic Heterogeneity; Humans; Neoplasms; Nuclear Proteins; Prognosis; Publication Bias; Survival Analysis; Twist-Related Protein 1; Up-Regulation
PubMed: 25429425
DOI: 10.3390/ijms151221621