Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Department of Urology, The Jikei University School of Medicine, Tokyo, Japan.
Urol Oncol. 2023 Jun;41(6):261-273. doi: 10.1016/j.urolonc.2023.04.003. Epub 2023 May 2.
This study aimed to assess both efficacy and safety outcomes of lowering the dose of BCG compared to intravesical chemotherapies in non-muscle-invasive bladder cancer (NMIBC) patients using a systematic review, meta-analysis, and network meta-analysis approach. A comprehensive literature search was performed through Pubmed®, Web of Science™, and Scopus® in December 2022 to identify randomized controlled trials comparing the oncologic and/or safety outcomes of reduced dose intravesical BCG and/or intravesical chemotherapies according to the Preferred Reporting Items for Systematic Review and Meta-analyses (PRISMA) statement. The outcomes of interest were risk of recurrence, progression, treatment-related adverse events, and discontinuation. Overall, 24 studies were eligible for quantitative synthesis. Among 22 studies that adopted induction followed by maintenance intravesical therapy, with reference to the lower-dose BCG, epirubicin was associated with a significantly higher risk of recurrence (Odds ratio [OR]: 2.82, 95% CI: 1.54-5.15), but not other intravesical chemotherapies. There were no significant differences in risk of progression among the intravesical therapies. On the other hand, standard-dose BCG was associated with a higher risk of any AEs (OR: 1.91, 95% CI: 1.07-3.41) but other intravesical chemotherapies had a comparable risk of AEs compared to lower-dose BCG. The discontinuation rate did not significantly differ between lower-dose and standard-dose BCG (OR: 1.40, 95% CI: 0.81-2.43) as well as other intravesical. According to the surface under the cumulative ranking curve, gemcitabine, and standard-dose BCG were preferable to lower-dose BCG in terms of recurrence risk; gemcitabine was also preferable to lower-dose BCG in terms of risk of AEs. In patients with NMIBC, lowering the dose of BCG decreases the risks of AEs and discontinuation rate compared to standard-dose BCG, but there is no difference in these endpoints compared to other intravesical chemotherapies. Standard-dose of BCG is preferred for all intermediate and high-risk NMIBC patients based on oncologic efficacy; however, lower-dose BCG and intravesical chemotherapies, especially gemcitabine, could be considered a reasonable alternative to BCG in selected patients who suffer from significant AEs or in case standard-dose BCG is not available.
本研究旨在通过系统评价、荟萃分析和网络荟萃分析方法，评估与膀胱内化学疗法相比，降低剂量的卡介苗（BCG）在非肌肉浸润性膀胱癌（NMIBC）患者中的疗效和安全性结果。通过 2022 年 12 月在 Pubmed®、Web of Science™和 Scopus®上进行全面的文献检索，以确定比较降低剂量膀胱内 BCG 和/或膀胱内化学疗法的肿瘤学和/或安全性结果的随机对照试验，这些试验符合系统评价和荟萃分析的首选报告项目（PRISMA）声明。感兴趣的结果是复发风险、进展风险、治疗相关不良事件和停药率。总体而言，有 24 项研究符合定量综合标准。在 22 项采用诱导后维持膀胱内治疗的研究中，与低剂量 BCG 相比，表柔比星与复发风险显著增加相关（优势比[OR]：2.82，95%置信区间[CI]：1.54-5.15），但与其他膀胱内化学疗法无显著差异。在膀胱内治疗中，进展风险无显著差异。另一方面，标准剂量 BCG 与任何不良事件（AE）的风险较高相关（OR：1.91，95%CI：1.07-3.41），但与低剂量 BCG 相比，其他膀胱内化学疗法的 AE 风险相当。低剂量和标准剂量 BCG 之间的停药率无显著差异（OR：1.40，95%CI：0.81-2.43），与其他膀胱内治疗也无显著差异。根据累积排序曲线下面积，吉西他滨和标准剂量 BCG 在复发风险方面优于低剂量 BCG；吉西他滨在 AE 风险方面也优于低剂量 BCG。在 NMIBC 患者中，与标准剂量 BCG 相比，降低 BCG 剂量可降低 AE 和停药率的风险，但与其他膀胱内化学疗法相比，这些终点无差异。基于肿瘤学疗效，所有中高危 NMIBC 患者均首选标准剂量 BCG；然而，对于患有严重 AE 的患者，或者在无法使用标准剂量 BCG 的情况下，低剂量 BCG 和膀胱内化学疗法，尤其是吉西他滨，可能是 BCG 的合理替代选择。
