Li Roger, Hensley Patrick J, Gupta Shilpa, Al-Ahmadie Hikmat, Babjuk Marko, Black Peter C, Brausi Maurizio, Bree Kelly K, Fernández Mario I, Guo Charles C, Horowitz Amir, Lamm Donald L, Lerner Seth P, Lotan Yair, Mariappan Paramananthan, McConkey David, Mertens Laura S, Mir Carmen, Ross Jeffrey S, O'Donnell Michael, Palou Joan, Pohar Kamal, Steinberg Gary, Soloway Mark, Spiess Philippe E, Svatek Robert S, Tan Wei Shen, Taoka Rikiya, Buckley Roger, Kamat Ashish M
Department of Genitourinary Oncology, H. Lee Moffitt Cancer Center, Tampa, FL, USA.
Department of Urology, University of Kentucky College of Medicine, Lexington, KY, USA.
Eur Urol. 2024 Dec;86(6):516-527. doi: 10.1016/j.eururo.2024.08.001. Epub 2024 Aug 24.
There has been a recent surge in the development of agents for bacillus Calmette-Guérin-unresponsive (BCG-U) non-muscle-invasive bladder cancer (NMIBC). Critical assessment of these agents and practical recommendations for optimal selection of patients and therapies are urgently needed, especially in the absence of randomized trials on bladder-sparing treatment (BST) options.
A global committee of bladder cancer experts was assembled to develop recommendations on BST for BCG-U NMIBC. Working groups reviewed the literature and developed draft recommendations, which were then voted on by International Bladder Cancer Group (IBCG) members using a modified Delphi process. During a live meeting in August 2023, voting results and supporting evidence were presented, and recommendations were refined on the basis of meeting discussions. Final recommendations achieved >75% agreement during the meeting, and some were further refined via web conferences and e-mail discussions.
There is currently no single optimal agent for patients with BCG-U disease who seek to avoid radical cystectomy (RC). BST selection should be personalized, taking into account individual patient characteristics and preferences, tumor attributes, and efficacy/toxicity data for the agents available. For patients with BCG-U carcinoma in situ (CIS), gemcitabine/docetaxel (GEM/DOCE), nadofaragene firadenovec (NFF), and nogapendekin alfa inbakicept-pmln (NAI) + BCG are recommended; because of its systemic toxicity, pembrolizumab should only be offered after other options are exhausted. For patients with BCG-U papillary-only tumors, GEM/DOCE, NFF, NAI + BCG, single-agent chemotherapy, hyperthermic mitomycin C, and pembrolizumab are recommended. Given the modest efficacy of available options, clinical trial participation is encouraged. For unapproved agents with reported data, IBCG recommendations await the final results of pivotal trials.
The IBCG consensus recommendations provide practical guidance on BST for BCG-U NMIBC.
近期，用于卡介苗无反应性（BCG-U）非肌肉浸润性膀胱癌（NMIBC）的治疗药物研发激增。迫切需要对这些药物进行严格评估，并就患者和治疗的最佳选择提出实用建议，尤其是在缺乏膀胱保留治疗（BST）方案随机试验的情况下。
组建了一个全球膀胱癌专家委员会，以制定关于BCG-U NMIBC的BST建议。工作组回顾了文献并制定了建议草案，然后国际膀胱癌小组（IBCG）成员使用改良的德尔菲法进行投票。在2023年8月的一次现场会议上，展示了投票结果和支持证据，并根据会议讨论对建议进行了完善。最终建议在会议期间达成了>75%的共识，一些建议通过网络会议和电子邮件讨论进一步完善。
对于寻求避免根治性膀胱切除术（RC）的BCG-U疾病患者，目前没有单一的最佳药物。BST的选择应个性化，考虑个体患者特征和偏好、肿瘤属性以及可用药物的疗效/毒性数据。对于BCG-U原位癌（CIS）患者，推荐使用吉西他滨/多西他赛（GEM/DOCE）、纳多福韦基因腺病毒载体（NFF）以及nogapendekin alfa inbakicept-pmln（NAI）+卡介苗；由于其全身毒性，帕博利珠单抗仅在其他选择都用尽后才考虑使用。对于仅为BCG-U乳头状肿瘤的患者，推荐使用GEM/DOCE、NFF、NAI+卡介苗、单药化疗、热灌注丝裂霉素C和帕博利珠单抗。鉴于现有方案疗效有限，鼓励患者参加临床试验。对于有报告数据的未获批药物，IBCG的建议有待关键试验的最终结果。
IBCG的共识建议为BCG-U NMIBC的BST提供了实用指导。
