Prognostic DNA Methylation Biomarkers in High-risk Non–muscle-invasive Bladder Cancer: A Systematic Review to Identify Loci for Prospective Validation

2020 ◽  
Vol 6 (4) ◽  
pp. 683-697 ◽  
Author(s):  
Pratik M.S. Gurung ◽  
Abigail R. Barnett ◽  
Jayne S. Wilson ◽  
John Hudson ◽  
Douglas G. Ward ◽  
...  
Keyword(s):  
Systematic Review ◽  
Dna Methylation ◽  
Bladder Cancer ◽  
High Risk ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Muscle Invasive

scholarly journals Application of intra-arterial chemotherapy in high-risk non-muscle invasive bladder cancer: a systematic review and meta-analysis

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e12248
Author(s):  
Chengyu You ◽  
Xianhui Li ◽  
Yuelin Du ◽  
Hui Wang ◽  
Xiaojun Zhang ◽  
...  
Keyword(s):  
Systematic Review ◽  
Bladder Cancer ◽  
High Risk ◽  
Death Rate ◽  
Meta Analysis ◽  
Invasive Bladder Cancer ◽  
Current Evidence ◽  
Muscle Invasive Bladder Cancer ◽  
Free Survival ◽  
Muscle Invasive

Background To summarize the current evidence on the effects of intra-arterial chemotherapy (IAC) on high-risk non-muscle invasive bladder cancer (NMIBC) and compare oncology results with intravesical chemotherapy (IVC). Methods We performed a systematic review and cumulative meta-analysis of the primary outcomes of interest by a systematical search of multiple scientific databases in February 2021. The mean difference (MD) and odds ratio (OR) were calculated for continuous and dichotomous variables respectively, with 95% confidence intervals (CIs). The hazard radio (HR) with 95% CIs was used for overall survival (OS), recurrence-free survival (RFS) and progression-free survival (PFS). Results A total of six studies with 866 patients were included. For IAC combined with IVC versus IVC alone, statistically significant differences were found regarding tumor recurrence rate (OR: 0.51, 95% CI [0.36∼0.72], p = 0.0001), tumor progression rate (OR: 0.47, 95% CI [0.30∼0.72], p = 0.0006), tumor-specific death rate (OR: 0.49, 95% CI [0.25∼0.99], p = 0.05), PFS (HR: 0.47, 95% CI [0.23∼0.96], p = 0.04) and RFS (HR: 0.60, 95% CI [0.41∼0.87], p = 0.007). No significant difference between two groups was found for time to first recurrence (MD: 3.27, 95% CI [−2.37∼8.92], p = 0.26) and OS (HR: 1.20, 95% CI [0.44∼3.32], p = 0.72). For IAC alone versus IVC, There was no statistical difference in the terms of tumor-specific death rate (OR: 0.67, 95% CI [0.29∼1.53], p = 0.34), RFS (HR: 0.90, 95% CI [0.56∼1.46], p = 0.68) and PFS (HR: 0.71, 95% CI [0.32∼1.55], p = 0.39). Adverse events mainly included nausea/vomiting (36.3%), hypoleukemia (19.4%), neutropenia (16.0%), increased creatinine (9.9%), increased alanine aminotransferase (18.7%), and thrombocytopenia (9.9%). Conclusion The IAC combined with IVC is a safe and effective treatment for high risk NMIBC, with lower rates of recurrence, progression, tumor-specific death, PFS and RFS, and with minor and tolerable events. The effectiveness of the IAC alone is parallel to the IVC alone.

scholarly journals 1459 Intravesical Chemohyperthermia Versus Bacillus Calmette-Guerin Instillation for Intermediate- And High-Risk Non-Muscle Invasive Bladder Cancer: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 108 (Supplement_6) ◽  
Author(s):  
H Zhao ◽  
V W S Chan ◽  
D Castellani ◽  
E O T Chan ◽  
W L K Ong ◽  
...  
Keyword(s):  
Systematic Review ◽  
Bladder Cancer ◽  
High Risk ◽  
Safety Profile ◽  
Meta Analysis ◽  
Sensitivity Analyses ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Free Survival ◽  
Muscle Invasive

Abstract Introduction Traditional intravesical chemotherapy instillations under room temperature post trans-urethral resection (TUR) of non-muscle invasive bladder cancer (NMIBC) have lower efficacies than maintenance BCG installations. Intravesical chemo-hyperthermia (CHT) at higher temperatures is developed to improve the efficacy of chemotherapy instillation. This systematic review aims to compare the use of CHT and BCG instillation post-TUR. Method The protocol of this review is registered on PROSPERO(CRD42020223277). A comprehensive literature search was performed on Medline, EMBASE, and Cochrane CENTRAL to identify studies comparing CHT and BCG post-TUR for intermediate- or high-risk NMIBC. Primary outcomes include recurrence-free survival (RFS) and progression-free survival (PFS). Secondary outcomes include adverse events (AE). Results From 2,375 identified records, four randomised control trials incorporating 327 patients were included for meta-analysis. The use of CHT was found to be non-inferior to BCG in RFS, PFS and AEs (Grades 1-3) (p > 0.05). Sensitivity analysis, excluding patients with BCG failures, show 24-36 months recurrence rate to be significantly lower in CHT group (RR 0.64, 95% CI 0.42-0.98, p = 0.04) compared to the BCG group. In patients without carcinoma in situ (CIS), RFS is also significantly better in CHT patients (HR 0.52, 95% CI 0.32- 0.85, p < 0.01). Safety profile remains non-inferior to the BCG group in sensitivity analyses. Quality of evidence across all outcomes ranged from moderate to low. Conclusions In well-selected patients, intravesical CHT has superior oncological outcomes and non-inferior safety profile when compared to BCG maintenance therapy for patients with intermediate- and high-risk NMIBC. CHT is a possible alternative treatment during BCG shortage.

scholarly journals HumanMethylation450K Array–Identified Biomarkers Predict Tumour Recurrence/Progression at Initial Diagnosis of High-risk Non-muscle Invasive Bladder Cancer

2018 ◽  
Vol 10 ◽  
pp. 1179299X1775192 ◽  
Author(s):  
Mark O Kitchen ◽  
Richard T Bryan ◽  
Richard D Emes ◽  
Christopher J Luscombe ◽  
KK Cheng ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Bladder Cancer ◽  
High Risk ◽  
Clinical Outcomes ◽  
Patient Management ◽  
Initial Diagnosis ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Genome Wide ◽  
Muscle Invasive

Background: High-risk non-muscle invasive bladder cancer (HR-NMIBC) is a clinically unpredictable disease. Despite clinical risk estimation tools, many patients are undertreated with intra-vesical therapies alone, whereas others may be over-treated with early radical surgery. Molecular biomarkers, particularly DNA methylation, have been reported as predictive of tumour/patient outcomes in numerous solid organ and haematologic malignancies; however, there are few reports in HR-NMIBC and none using genome-wide array assessment. We therefore sought to identify novel DNA methylation markers of HR-NMIBC clinical outcomes that might predict tumour behaviour at initial diagnosis and help guide patient management. Patients and methods: A total of 21 primary initial diagnosis HR-NMIBC tumours were analysed by Illumina HumanMethylation450 BeadChip arrays and subsequently bisulphite Pyrosequencing. In all, 7 had not recurred at 1 year after resection and 14 had recurred and/or progressed despite intra-vesical BCG. A further independent cohort of 32 HR-NMIBC tumours (17 no recurrence and 15 recurrence and/or progression despite BCG) were also assessed by bisulphite Pyrosequencing. Results: Array analyses identified 206 CpG loci that segregated non-recurrent HR-NMIBC tumours from clinically more aggressive recurrence/progression tumours. Hypermethylation of CpG cg11850659 and hypomethylation of CpG cg01149192 in combination predicted HR-NMIBC recurrence and/or progression within 1 year of diagnosis with 83% sensitivity, 79% specificity, and 83% positive and 79% negative predictive values. Conclusions: This is the first genome-wide DNA methylation analysis of a unique HR-NMIBC tumour cohort encompassing known 1-year clinical outcomes. Our analyses identified potential novel epigenetic markers that could help guide individual patient management in this clinically unpredictable disease.

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