Artiles Medina Alberto, Subiela José Daniel, Pichler Renate, Guerrero-Ramos Felix, Burgos Revilla Francisco Javier
Department of Urology, Hospital Universitario Ramón y Cajal, IRYCIS, Universidad de Alcala, Madrid.
Medical University of Innsbruck, Department of Urology, Comprehensive Cancer Center Innsbruck (CCCI), Innsbruck, Austria.
Curr Opin Urol. 2025 Jul 14. doi: 10.1097/MOU.0000000000001319.
Bacillus Calmette-Guérin (BCG) remains the standard of care for high-risk non-muscle-invasive bladder cancer (NMIBC), yet up to 40-50% of patients experience treatment failure, leaving limited alternatives to avoid radical cystectomy. This narrative review critically examines both traditional and emerging BCG-based strategies - including repeat induction and modern combination regimens - for patients with BCG-unresponsive NMIBC.
BCG monotherapy after BCG failure has shown limited effectiveness, with recent studies reporting 12-month disease-free survival (DFS) rates of 60-70%. Nonetheless, BCG continues to serve as an immunotherapeutic backbone in combination strategies. Chemo-immunotherapy regimens, particularly those using gemcitabine or mitomycin C, have achieved 1-year DFS rates of up to 80%. Combinations with cytokines and immunocytokines - such as interferon-α or nogapendekin alfa inbakicept-pmln (NAI) - have demonstrated DFS rates of 45-61%, and NAI has recently received FDA approval. Immune checkpoint inhibitors (e.g., pembrolizumab, durvalumab, atezolizumab) in combination with BCG have shown DFS rates ranging from 42 to 73% at 12 months. However, many studies are limited by small sample sizes and heterogeneous designs.
Despite its limited efficacy as monotherapy in unresponsive cases, BCG retains therapeutic relevance as part of combination strategies that enhance its immunologic activity. Emerging data suggest that these BCG-based regimens offer a promising, bladder-sparing alternative for patients who are ineligible for or decline radical cystectomy. Ongoing and future trials will be essential to define optimal combinations and identify which patients are most likely to benefit, thereby enabling appropriate patient selection.
卡介苗（BCG）仍然是高危非肌层浸润性膀胱癌（NMIBC）的标准治疗方法，但高达40%-50%的患者会出现治疗失败，避免根治性膀胱切除术的替代方案有限。本叙述性综述批判性地研究了针对BCG无反应的NMIBC患者的传统和新兴的基于BCG的策略，包括重复诱导和现代联合方案。
BCG失败后采用BCG单药治疗显示效果有限，最近的研究报告12个月无病生存率（DFS）为60%-70%。尽管如此，BCG在联合策略中仍然是免疫治疗的支柱。化学免疫治疗方案，特别是使用吉西他滨或丝裂霉素C的方案，1年DFS率高达80%。与细胞因子和免疫细胞因子联合使用——如干扰素-α或诺加彭德金α英巴凯普特-pmln（NAI）——DFS率为45%-61%，NAI最近已获得美国食品药品监督管理局（FDA）批准。免疫检查点抑制剂（如帕博利珠单抗、度伐利尤单抗、阿替利珠单抗）与BCG联合使用，12个月时DFS率为42%-73%。然而，许多研究受样本量小和设计异质性的限制。
尽管BCG在无反应病例中作为单药治疗疗效有限，但作为增强其免疫活性的联合策略的一部分，BCG仍具有治疗意义。新出现的数据表明，这些基于BCG的方案为不符合根治性膀胱切除术条件或拒绝接受根治性膀胱切除术的患者提供了一种有前景的保留膀胱的替代方案。正在进行的和未来的试验对于确定最佳联合方案以及确定哪些患者最可能受益至关重要，从而能够进行适当的患者选择。
