Re-analysis of intravesical gemcitabine in the era of Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle-invasive bladder cancer.

IF 2.3 3区医学 Q3 ONCOLOGY

Urologic Oncology-seminars and Original Investigations Pub Date : 2025-05-24 DOI:10.1016/j.urolonc.2025.04.006

Manuel R De Jesus Escano, Emily A Vertosick, Neeta D'Souza, Nicole Benfante, Andrew T Lenis, Peter A Reisz, Christopher Gaffney, Alvin Goh, Timothy F Donahue, Eugene Cha, S Machele Donat, Harry W Herr, Guido Dalbagni, Dean Bajorin, Judy Sarungbam, Hikmat Al-Ahmadie, Bernard H Bochner, Daniel D Sjoberg, Eugene J Pietzak

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引用次数: 0

Abstract

Purpose: Uncertainty exits over the best treatments for patients whom Bacillus Calmette-Guérin (BCG) has failed. We aim to contextualize novel therapies approved based on single-arm, nonrandomized trials and those supported only by retrospective data by re-analyzing oncologic outcomes achieved with intravesical gemcitabine.

Materials and methods: Patients with non-muscle-invasive bladder cancer (NMIBC) who were treated for BCG failure with single agent intravesical gemcitabine at our institution were analyzed to compare clinical outcomes (high-grade recurrence/progression) across different BCG failure definitions. Associations between clinicopathologic variables with outcomes after gemcitabine were estimated using Cox models.

Results: Of the 127 patients, 57% met the historical definition of BCG-refractory NMIBC and 33% met BCG-unresponsive criteria using a 12-month cut-off. Twelve-month recurrence-free survival was similar between BCG-refractory (47%; 95% CI: 36%, 60%) and BCG-unresponsive (52%; 95% CI: 38%, 71%) definitions. BCG-unresponsive patients who received gemcitabine in a clinical trial had significantly worse recurrence-free survival compared to those receiving the same treatment outside a trial (12-month recurrence-free survival difference: 41%; P = 0.02). A positive pretreatment urine cytology was associated with increased risk of recurrence (P = 0.005) and progression (P = 0.002) and may better indicate minimal residual disease than carcinoma in-situ on pretreatment biopsies.

Conclusions: Our data raise concern over US Food and Drug Administration approval based on single-arm, nonrandomized trials using expert-based BCG-unresponsive criteria and for the use of combination gemcitabine-docetaxel as a de facto standard treatment based on retrospective data alone. Improved assessments of minimal residual disease, such as pretreatment urinary cytology, are needed to improve risk stratification in NMIBC.

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吉西他滨在卡介苗-卡介苗-无反应性非肌侵性膀胱癌时代的再分析。

目的：卡介苗治疗无效的最佳治疗方案存在不确定性。我们的目标是通过重新分析膀胱内注射吉西他滨获得的肿瘤学结果，将基于单臂、非随机试验和仅由回顾性数据支持的新疗法纳入背景。材料和方法：对我院接受单药膀胱内吉西他滨治疗卡介苗失败的非肌浸润性膀胱癌（NMIBC）患者进行分析，比较不同卡介苗失败定义的临床结果（高级别复发/进展）。使用Cox模型估计吉西他滨后临床病理变量与预后之间的关系。结果：在127例患者中，57%符合bcg难治性NMIBC的历史定义，33%符合bcg无反应标准。bcg难治性患者的12个月无复发生存率相似(47%；95% CI: 36%, 60%)和bcg无反应(52%；95% CI: 38%, 71%)定义。与在临床试验外接受相同治疗的患者相比，在临床试验中接受吉西他滨治疗的bcg无反应患者的无复发生存期明显更差(12个月无复发生存期差异：41%； = 0.02页)。预处理尿细胞学阳性与复发（P = 0.005）和进展（P = 0.002）的风险增加相关，并且在预处理活检中可能比原位癌更好地提示微小残留疾病。结论：我们的数据引起了美国食品和药物管理局对单臂非随机试验的关注，该试验采用专家为基础的bcg无反应标准，并且仅基于回顾性数据将吉西他滨-多西他赛联合使用作为事实上的标准治疗。需要改进对微小残留疾病的评估，如预处理尿细胞学，以改善NMIBC的风险分层。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Urologic Oncology-seminars and Original Investigations 医学-泌尿学与肾脏学

CiteScore

4.80

自引率

3.70%

发文量

297

审稿时长

7.6 weeks

期刊介绍： Urologic Oncology: Seminars and Original Investigations is the official journal of the Society of Urologic Oncology. The journal publishes practical, timely, and relevant clinical and basic science research articles which address any aspect of urologic oncology. Each issue comprises original research, news and topics, survey articles providing short commentaries on other important articles in the urologic oncology literature, and reviews including an in-depth Seminar examining a specific clinical dilemma. The journal periodically publishes supplement issues devoted to areas of current interest to the urologic oncology community. Articles published are of interest to researchers and the clinicians involved in the practice of urologic oncology including urologists, oncologists, and radiologists.