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

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.

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

British Journal of Surgery ◽

10.1093/bjs/znab259.955 ◽

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.

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