Background/Objectives: Systemic immunotherapy, previously used mainly for advanced urothelial carcinoma, now plays an important role in the treatment of non-muscle invasive bladder cancer (NMIBC), either alone or combined with intravesical BCG instillations. Methods: We conducted a collaborative, comprehensive review to summarize the key evidence and future perspectives on therapeutic intensification strategies involving immune checkpoint inhibitors in NMIBC. A total of 51 references published between 2000 and 2025 were included. Results: Four phase II studies evaluated pembrolizumab, atezolizumab, durvalumab, and cetrelimab as monotherapy in 28 to 132 BCG-unresponsive NMIBC patients. They reported complete response rates ranging from 12% to 43% after 3 to 12 months of treatment, with a durable response rate ranging from 49% to 57.4% at 12 months. To improve these results, a phase II trial launched this year tests a new systemic combination targeting both the PD-1/PD-L1 axis and the emerging HLA-E/NKG2A pathway. Regarding BCG-naïve high-risk (HR) NMIBC, four phase III studies are evaluating BCG instillations combined with systemic immunotherapy: sasanlimab (CREST), durvalumab (POTOMAC), atezolizumab (ALBAN), and pembrolizumab (KEYNOTE-676), with significant results reported for the CREST and POTOMAC trials. The key challenge remains selecting patients most likely to benefit from this combination therapy while avoiding overtreatment. Identifying predictive biomarkers of tumor aggressiveness and response to immunotherapy also represents a major future challenge. Conclusions: Therapeutic intensification using systemic immunotherapy applies to both BCG-unresponsive NMIBC, with a new target pathway (HLA-E/NKG2A), and BCG-naïve HR NMIBC, where the combination of BCG instillations and immunotherapy represents a major breakthrough.
背景/目的：系统性免疫治疗既往主要用于晚期尿路上皮癌，如今在非肌层浸润性膀胱癌（NMIBC）的治疗中发挥着重要作用，既可单独应用，亦可与膀胱内卡介苗灌注联合使用。方法：我们通过协作完成全面综述，总结NMIBC领域涉及免疫检查点抑制剂的治疗强化策略的关键证据与未来展望。共纳入2000年至2025年间发表的51篇参考文献。结果：四项II期研究分别评估了帕博利珠单抗、阿替利珠单抗、度伐利尤单抗及西曲利单抗作为单药疗法在28至132例卡介苗无应答NMIBC患者中的应用。研究显示治疗3至12个月后完全缓解率为12%至43%，12个月时持续缓解率达49%至57.4%。为提升疗效，今年启动的一项II期试验正在测试一种同时靶向PD-1/PD-L1轴与新兴HLA-E/NKG2A通路的新型全身联合方案。针对未接受过卡介苗治疗的高危NMIBC，四项III期研究正在评估卡介苗灌注联合系统性免疫治疗的方案：包括沙森利单抗（CREST研究）、度伐利尤单抗（POTOMAC研究）、阿替利珠单抗（ALBAN研究）和帕博利珠单抗（KEYNOTE-676研究），其中CREST与POTOMAC试验已报告显著成果。当前核心挑战在于精准筛选最可能从此联合疗法中获益的患者，同时避免过度治疗。识别肿瘤侵袭性及免疫治疗应答的预测性生物标志物，亦是未来面临的重要课题。结论：系统性免疫治疗强化策略适用于两类NMIBC患者：针对卡介苗无应答型患者，新兴靶向通路（HLA-E/NKG2A）展现出潜力；对于未接受过卡介苗治疗的高危患者，卡介苗灌注与免疫治疗的联合方案代表了重大突破。
肿瘤(癌症)患者之家