Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Epidemiology, School of Public Health, Fudan University, Shanghai, China.
Cancer Med. 2020 Nov;9(21):7800-7809. doi: 10.1002/cam4.3513. Epub 2020 Oct 11.
Intravesical instillation therapy is the mainstay of prophylaxis of tumor recurrence and progression in non-muscle-invasive bladder cancer. However, there is no study evaluating the superiority of monotherapy. The aim of this study is to compare the efficacy of preventing recurrence and progression of intravesical monotherapies via network meta-analysis (NMA) of randomized controlled trials. Database searches were conducted on Embase, Ovid Medline, Web of Science, ScienceDirect, Cochrane Library, and ClinicalTrials.com from the time of establishment to February 6, 2020. The monotherapies included Bacille Calmette-Guérin (BCG), mitomycin C (MMC), interferon (IFN), adriamycin, epirubicin, gemcitabine (GEM), and thiotepa (THP). A Bayesian consistency network model was generated under a random-effects model. The superiority of therapy was identified based on the surface under the cumulative ranking curve (SUCRA). Fifty-seven studies with 12462 patients are included. NMA shows that GEM (SUCRA = 0.92), BCG (SUCRA = 0.82), and IFN (SUCRA = 0.78) are the top three effective drugs to reduce recurrence. GEM (SUCRA = 0.87) is the most effective therapy to prevent progress, followed by BCG, MMC, THP, and IFN with similar efficacy. Subgroup analysis of pairwise meta-analysis and NMA was performed on publication year, trial initiation year, study origin, center involvement, sample size, drug schedule, tumor characteristics, and trial quality to address confounding factors, which suggests the robustness of the results with stable effect sizes. Network meta-regression also indicates consistent rank by analyzing year, sample size, and quality. Compared with BCG, GEM is also a promising therapy with favorable efficacy to reduce tumor recurrence and progression. IFN and MMC could be alternative therapies for BCG with slightly inferior efficacy in recurrence prevention and similar efficacy in progression prevention. However, the results of this study should be treated with caution since most of the included studies are of moderate to high risk of bias.
膀胱内灌注治疗是非肌层浸润性膀胱癌肿瘤复发和进展的主要预防手段。然而，目前尚无研究评估单药治疗的优势。本研究旨在通过对随机对照试验的网络荟萃分析（NMA）比较膀胱内单药治疗预防复发和进展的疗效。从建立数据库到 2020 年 2 月 6 日，我们在 Embase、Ovid Medline、Web of Science、ScienceDirect、Cochrane Library 和 ClinicalTrials.com 上进行了数据库检索。纳入的单药治疗包括卡介苗（BCG）、丝裂霉素 C（MMC）、干扰素（IFN）、阿霉素、表柔比星、吉西他滨（GEM）和噻替派（THP）。采用随机效应模型生成贝叶斯一致性网络模型。根据累积排序曲线下面积（SUCRA）确定治疗的优越性。纳入了 57 项研究，共 12462 例患者。NMA 显示，GEM（SUCRA=0.92）、BCG（SUCRA=0.82）和 IFN（SUCRA=0.78）是降低复发的前三种有效药物。GEM（SUCRA=0.87）是预防进展最有效的治疗方法，其次是 BCG、MMC、THP 和 IFN，疗效相似。对发表年份、试验启动年份、研究来源、中心参与、样本量、药物方案、肿瘤特征和试验质量进行了成对荟萃分析和 NMA 的亚组分析，以解决混杂因素，结果表明，效果大小稳定，结果具有稳健性。网络荟萃回归分析也表明，通过分析年份、样本量和质量，排名一致。与 BCG 相比，GEM 也是一种有前途的治疗方法，具有降低肿瘤复发和进展的良好疗效。IFN 和 MMC 可能是 BCG 的替代疗法，在预防复发方面效果稍差，但在预防进展方面效果相似。然而，由于纳入的大多数研究存在中高度偏倚风险，因此应谨慎对待本研究的结果。
