Longoni Mattia, Scilipoti Pietro, Soria Francesco, Pradere Benjamin, Krajewski Wojciech, D'Andrea David, Mari Andrea, Del Giudice Francesco, Pichler Renate, Subiela José Daniel, Afferi Luca, Albisinni Simone, Gallioli Andrea, Mertens Laura S, Laukhtina Ekaterina, Mori Keiichiro, Radziszewski Piotr, Ślusarczyk Aleksander, Shariat Shahrokh F, Necchi Andrea, Xylinas Evanguelos, Gontero Paolo, Rouprêt Morgan, Montorsi Francesco, Briganti Alberto, Moschini Marco
Unit of Urology/Division of Oncology, Gianfranco Soldera Prostate Cancer Lab, IRCCS San Raffaele Scientific Institute, Milan, Italy; "Vita-Salute" San Raffaele University, Milan, Italy.
Division of Urology, Department of Surgical Sciences, San Giovanni Battista Hospital, University of Studies of Torino, Turin, Italy.
Eur Urol Oncol. 2025 Apr 8. doi: 10.1016/j.euo.2025.03.007.
Bacillus Calmette-Guérin (BCG) is the standard treatment in patients harboring high-risk (HR) non-muscle-invasive bladder cancer (NMIBC). However, BCG therapy faces frequent adverse events (AEs), limited efficacy, and ongoing shortages, leading to a low completion rate, access challenges, and high recurrence. In consequence, there is a growing interest in exploring alternative treatments, including immune checkpoint inhibitors, chemotherapy combinations, and novel intravesical therapies. This systematic review summarizes current prospective evidence on BCG and alternative treatment options for BCG-naïve HR-NMIBC patients (PROSPERO: CRD42024564900).
A systematic search in MEDLINE, EMBASE, Scopus, Web of Science, and Cochrane Library retrieved 1042 studies, of which 17 met the inclusion criteria (following the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines).
In 12 studies on BCG-treated patients (n = 1418), recurrence-free survival (RFS) rates were 66-96% at 1-yr, 63-96% at 2-yr, and 39-66% at 5-yr follow-up. Progression-free survival (PFS) rates were 81-98% at 1-yr, 70-96% at 2-yr, and 70-84% at 5-yr follow-up. In nine studies focusing on patients treated with alternative strategies (n = 657), RFS rates were 51-99% at 1-yr, 48-88% at 2-yr, and 47-55% at 5-yr follow-up. PFS was 90-100% at 1-yr, 88-96% at 2-yr, and 84-93% at 5-yr follow-up. AE rates varied widely across studies, for both BCG and alternative treatments. Unfortunately, studies heterogeneity and a small sample sizes limit statistically meaningful conclusions. Twelve clinical trials are currently investigating new strategies for BCG-naïve HR NMIBC patients.
Alternative therapies for BCG-naïve HR NMIBC patients are emerging but need further validation. As challenges such as toxicity, cost, and long-term efficacy persist, ongoing trial results will be crucial in determining their role in future clinical practice.
卡介苗（BCG）是高危（HR）非肌层浸润性膀胱癌（NMIBC）患者的标准治疗方法。然而，卡介苗治疗面临着频繁的不良事件（AE）、疗效有限以及持续短缺的问题，导致完成率低、获取困难和高复发率。因此，人们对探索替代治疗方法的兴趣日益浓厚，包括免疫检查点抑制剂、化疗联合方案和新型膀胱内治疗。本系统评价总结了目前关于初治HR-NMIBC患者使用卡介苗及替代治疗方案的前瞻性证据（国际前瞻性系统评价注册库：CRD42024564900）。
在MEDLINE、EMBASE、Scopus、Web of Science和Cochrane图书馆进行系统检索，共检索到1042项研究，其中17项符合纳入标准（遵循系统评价和Meta分析的首选报告项目指南）。
在12项关于卡介苗治疗患者的研究（n = 1418）中，1年无复发生存（RFS）率为66%-96%，2年为63%-96%，5年为39%-66%。1年无进展生存（PFS）率为81%-98%，2年为70%-96%，5年为70%-84%。在9项关注替代策略治疗患者的研究（n = 657）中，1年RFS率为51%-99%；2年为48%-88%，5年为47%-55%。1年PFS为90%-100%，2年为88%-96%，5年为84%-93%。卡介苗和替代治疗的不良事件发生率在各研究中差异很大。遗憾的是，研究的异质性和小样本量限制了具有统计学意义的结论。目前有12项临床试验正在研究初治HR NMIBC患者的新策略。
初治HR NMIBC患者的替代疗法正在兴起，但需要进一步验证。由于毒性、成本和长期疗效等挑战依然存在，正在进行的试验结果对于确定它们在未来临床实践中的作用至关重要。
