此页面是自动翻译的，不保证翻译的准确性。请参阅英文版对于源文本。

Perioperative Systemic Therapies in Muscle-Invasive Bladder Cancer (GUARDIANS) (GUARDIANS)

2026年10月1日更新者：Can Aydogdu, MD、LMU Klinikum

Perioperative GUARDIANS Project: Real-World Evaluation of Feasibility, Toxicity, and Oncologic Outcomes of Perioperative Systemic Therapies in Muscle-Invasive Urothelial Carcinoma

This is a multicenter, non-interventional, prospective and retrospective observational patient registry study of adults with muscle-invasive bladder cancer receiving perioperative systemic therapy as part of routine clinical care. The registry includes patients treated with perioperative systemic therapies such as Enfortumab Vedotin plus Pembrolizumab as well as cisplatin-based combinations including Gemcitabine/Cisplatin/Durvalumab and other standard perioperative treatment approaches in the neoadjuvant and adjuvant setting.

The study aims to evaluate real-world feasibility, treatment tolerability, pathologic response, and oncologic outcomes of perioperative systemic treatment strategies. Key outcomes include event-free survival (EFS), pathologic complete response (pCR), pathologic downstaging, disease-free survival (DFS), overall survival (OS), perioperative complications, and treatment-related adverse events. Patient-reported neurotoxicity symptoms will also be assessed using standardized neuropathy questionnaires.

All treatments, surgeries, and follow-up procedures are performed according to routine clinical practice. No study-specific interventions are assigned. Clinical data are collected pseudonymized through participating GUARDIANS centers using standardized electronic case report forms. Both prospective and retrospective data collection are included.

研究概览

地位

招聘中

条件

干预/治疗

其他：Perioperative Systemic Therapy Registry

详细说明

The GUARDIANS perioperative registry is a multicenter observational study designed to collect real-world data on perioperative systemic therapies in patients with muscle-invasive or locally advanced urothelial carcinoma of the bladder.

Perioperative systemic treatment strategies for muscle-invasive bladder cancer are rapidly evolving and include antibody-drug conjugate-based combinations such as Enfortumab Vedotin plus Pembrolizumab as well as cisplatin-based regimens including Gemcitabine/Cisplatin/Durvalumab and other standard neoadjuvant and adjuvant treatment approaches. While these regimens are increasingly used in routine care, systematic real-world evidence regarding feasibility, dose intensity, perioperative safety, patient-reported neurotoxicity, pathologic response, and long-term oncologic outcomes remains limited.

This registry evaluates perioperative treatment strategies with particular focus on real-world implementation, treatment completion, and comparative outcomes across different systemic therapy approaches. Patients are followed longitudinally from baseline and diagnosis through neoadjuvant therapy, radical cystectomy with pelvic lymph node dissection, adjuvant therapy when applicable, and long-term follow-up.

The primary objective is evaluation of event-free survival (EFS) and treatment feasibility. Feasibility includes completion of intended radical cystectomy, delivery of planned neoadjuvant and adjuvant treatment components, and reasons for treatment delay, modification, or discontinuation.

Secondary objectives include assessment of:

Pathologic complete response (pCR, ypT0N0) Pathologic downstaging Disease-free survival (DFS) Overall survival (OS) Local and distant recurrence patterns 90-day postoperative complications after radical cystectomy CTCAE version 5.0 treatment-related toxicities Patient-reported chemotherapy-induced peripheral neuropathy symptoms Treatment exposure and dose intensity The study is non-interventional. All diagnostic and therapeutic decisions are made independently of study participation according to local standard of care. No additional mandatory visits, diagnostic procedures, or therapeutic interventions are required.

Data are collected pseudonymized using REDCap across participating GUARDIANS centers. Prospective collection includes patient-reported outcome measures for neurotoxicity, while retrospective collection allows inclusion of previously treated patients according to ethics approval and local regulations. The registry supports evaluation of real-world outcomes across multiple perioperative treatment strategies and provides comparative evidence for routine clinical practice.

研究类型

观察性的

注册 (估计的)

500

联系人和位置

本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。

学习地点

德国
- - Munich、德国、81377
    - 招聘中
    - Department of Urology, LMU University Hospital Munich
    - 接触：
      
      Can Aydogdu, MD
      
      电话号码：+49 89 4400 0
      
      邮箱：can.aydogdu@med.uni-muenchen.de

参与标准

研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

18年及以上 (成人、年长者)

接受健康志愿者

不

有资格学习的性别

全部

取样方法

非概率样本

研究人群

Adult patients with muscle-invasive or locally advanced urothelial carcinoma of the bladder receiving perioperative systemic therapy in routine clinical practice. Patients are treated in the neoadjuvant and/or adjuvant setting with curative intent and undergo or are planned for radical cystectomy with pelvic lymph node dissection. Treatment approaches include Enfortumab Vedotin plus Pembrolizumab, Gemcitabine/Cisplatin/Durvalumab, cisplatin-based chemotherapy, immunotherapy, and other standard perioperative systemic therapies. Both prospective and retrospective patients from participating GUARDIANS centers are included.

描述

Inclusion Criteria:

Age ≥18 years
Histologically confirmed muscle-invasive or locally advanced urothelial carcinoma of the bladder
Planned, ongoing, or completed perioperative systemic therapy, including but not limited to Enfortumab Vedotin plus Pembrolizumab, Gemcitabine/Cisplatin/Durvalumab, cisplatin-based chemotherapy, immunotherapy, or other standard perioperative treatment approaches
Radical cystectomy planned or performed as part of curative-intent treatment strategy
Written informed consent for prospective data collection, where required
Sufficient clinical documentation available for retrospective inclusion, including at least one follow-up assessment

Exclusion Criteria:

Missing informed consent where prospectively required
Insufficient documentation of key baseline data or treatment exposure
No perioperative systemic therapy or inability to assign patient to a study cohort
Follow-up data unavailable or inconsistent documentation preventing endpoint assessment

学习计划

本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。

研究是如何设计的？

设计细节

观测模型：COHORT
时间观点：PROSPECTIVE

研究衡量的是什么？

主要结果指标

结果测量	大体时间
Event Free Survival (EFS) 大体时间：From treatment initiation up to 36 months	From treatment initiation up to 36 months

次要结果测量

结果测量	措施说明	大体时间
Pathologic Complete Response (pCR) 大体时间：At radical cystectomy		At radical cystectomy
Pathologic Downstaging 大体时间：At radical cystectomy	Defined as less than ypT2N0 in the cystectomy specimen, including pT0, pTis, pTa, and pT1.	At radical cystectomy
Disease-Free Survival (DFS) 大体时间：Up to 36 months after surgery	Time from curative surgery until recurrence or death.	Up to 36 months after surgery
Overall Survival (OS) 大体时间：Up to 60 months	Time from treatment initiation until death from any cause.	Up to 60 months
Change Over Time in Patient-Reported Peripheral Neuropathy Assessed by the EORTC QLQ-CIPN20 大体时间：Baseline; within 14 days before radical cystectomy; start of adjuvant therapy ±14 days; weeks 12, 21, and 30 of adjuvant therapy ±14 days; and end of treatment ±14 days	Patient-reported peripheral neuropathy symptoms will be assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Chemotherapy-Induced Peripheral Neuropathy 20 (EORTC QLQ-CIPN20). The questionnaire assesses sensory, motor, and autonomic symptoms of peripheral neuropathy. Subscale scores are calculated according to the EORTC scoring procedure and linearly transformed to a scale ranging from 0 to 100. Higher scores indicate greater peripheral neuropathy symptom burden and therefore a worse outcome. Changes from baseline will be assessed longitudinally during perioperative treatment through end of treatment.	Baseline; within 14 days before radical cystectomy; start of adjuvant therapy ±14 days; weeks 12, 21, and 30 of adjuvant therapy ±14 days; and end of treatment ±14 days
Treatment-Related Adverse Events 大体时间：From first administration of neoadjuvant therapy through the end-of-treatment visit, up to approximately 12 months	Occurrence, type, severity, attribution, management, and outcome of treatment-related adverse events associated with perioperative enfortumab vedotin and pembrolizumab. Adverse event severity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 5.0.	From first administration of neoadjuvant therapy through the end-of-treatment visit, up to approximately 12 months
90-Day Postoperative Complications 大体时间：Up to 90 days after radical cystectomy	Occurrence and severity of postoperative complications within 90 days after radical cystectomy, graded according to the Clavien-Dindo classification.	Up to 90 days after radical cystectomy
90-Day Perioperative Mortality 大体时间：Up to 90 days after radical cystectomy	All-cause mortality occurring within 90 days after radical cystectomy following perioperative systemic therapy. This includes deaths related to surgical complications, treatment-related toxicity, or other causes during the perioperative period.	Up to 90 days after radical cystectomy

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

赞助

LMU Klinikum

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始 (实际的)

2026年5月17日

初级完成 (估计的)

2026年12月31日

研究完成 (估计的)

2029年5月31日

研究注册日期

首次提交

2026年5月17日

首先提交符合 QC 标准的

2026年10月1日

首次发布 (实际的)

2026年10月2日

研究记录更新

最后更新发布 (实际的)