The Evolving Landscape of Systemic Immunotherapy for Bacillus Calmette-Guérin–naïve High-risk Non–muscle-invasive Bladder Cancer: At the Edge of a Tsunami?

IF 9.3 1区医学 Q1 ONCOLOGY

European urology oncology Pub Date : 2025-08-01 DOI:10.1016/j.euo.2025.06.003

Pierre-Etienne Gabriel , Mathieu Roumiguié , Gautier Marcq , Yves Allory , François Audenet , Anne Sophie Bajeot , Priscilla Leon , Alexandra Masson-Lecomte , Benjamin Pradère , Thomas Seisen , Constance Thibault , Morgan Rouprêt , Evanguelos Xylinas , for the Cancer Committee of The French Association of Urology (CC-AFU)

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引用次数: 0

Abstract

Background and objective

Treatment options for high-risk (HR) non–muscle-invasive bladder cancer (NMIBC) are still limited. The addition of systemic immunotherapy to intravesical bacillus Calmette-Guérin (BCG) instillations is currently being explored as an initial strategy for BCG-naïve HR NMIBC patients to enhance treatment effectiveness and decrease the risk of BCG failure.

Methods

A collaborative narrative review of the literature by the Cancer Committee of the French Association of Urology (CC-AFU) was carried out to describe ongoing studies assessing systemic immunotherapy in BCG-naïve HR NMIBC patients, focus on the different study designs, and evaluate the clinical pertinence of the endpoints. In total, 37 references published between 2003 and 2025 were included in our review.

Key findings and limitations

The ongoing phase 3 trials in BCG-naïve HR NMIBC patients include CREST (sasanlimab; NCT04165317), ALBAN (atezolizumab; NCT03799835), POTOMAC (durvalumab; NCT03528694), KEYNOTE-676 (pembrolizumab; NCT03711032), and SunRISe-3 (cetrelimab; NCT05714202). These five randomized, multicenter, multinational, open-label studies are evaluating the efficacy and safety of systemic intravenous or subcutaneous immunotherapy in combination with intravesical BCG, or in combination with TAR-200 in SunRISe-3, compared with BCG alone in BCG-naïve HR NMIBC patients. Recently, the CREST and POTOMAC studies demonstrated statistically significant and clinically meaningful improvements in event-free and disease-free survival, respectively, heralding a new therapeutic era in this field. Other results from these studies are expected between 2025 and 2030.

Conclusions and clinical implications

The combination of systemic immunotherapy with intravesical BCG instillations is being investigated and may become a new therapeutic strategy for BCG-naïve HR NMIBC.

查看原文本刊更多论文

芽孢杆菌系统免疫治疗的发展前景Calmette-Guérin-naïve高危非肌肉浸润性膀胱癌：在海啸的边缘？

背景和目的：高风险（HR）非肌肉浸润性膀胱癌（NMIBC）的治疗选择仍然有限。目前正在探索将全身免疫治疗添加到膀胱内卡介苗（BCG）注射中，作为BCG-naïve HR NMIBC患者的初始策略，以提高治疗效果并降低卡介苗失败的风险。方法：由法国泌尿外科协会癌症委员会（CC-AFU）对文献进行协作性叙述性回顾，描述正在进行的研究，评估BCG-naïve HR NMIBC患者的全身免疫治疗，重点关注不同的研究设计，并评估终点的临床相关性。我们的综述共纳入了2003年至2025年间发表的37篇参考文献。主要发现和局限性：正在进行的BCG-naïve HR NMIBC患者的3期试验包括CREST (sasanlimab；NCT04165317), ALBAN (atezolizumab；NCT03799835), POTOMAC (durvalumab；NCT03528694), KEYNOTE-676 (pembrolizumab；NCT03711032)和SunRISe-3 (cetrelimab；NCT05714202)。这五项随机、多中心、多国、开放标签的研究正在评估全身静脉或皮下免疫治疗联合膀胱内卡介苗，或在rise -3中联合ar -200，与单独卡介苗在BCG-naïve HR NMIBC患者中的疗效和安全性。最近，CREST和POTOMAC研究分别证明了无事件和无病生存的统计学意义和临床意义的改善，预示着该领域的一个新的治疗时代。这些研究的其他结果预计将在2025年至2030年之间公布。结论和临床意义：正在研究全身免疫治疗联合膀胱内注射卡介苗，可能成为BCG-naïve HR NMIBC的一种新的治疗策略。

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来源期刊

European urology oncology Multiple-

CiteScore

15.50

自引率

2.40%

发文量

128

审稿时长

20 days

期刊介绍： Journal Name: European Urology Oncology Affiliation: Official Journal of the European Association of Urology Focus: First official publication of the EAU fully devoted to the study of genitourinary malignancies Aims to deliver high-quality research Content: Includes original articles, opinion piece editorials, and invited reviews Covers clinical, basic, and translational research Publication Frequency: Six times a year in electronic format