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

1 октября 2026 г. обновлено: 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.

Обзор исследования

Статус

Рекрутинг

Условия

Вмешательство/лечение

Другой: Perioperative Systemic Therapy Registry

Подробное описание

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.

Тип исследования

Наблюдательный

Регистрация (Оцененный)

500

Контакты и местонахождение

В этом разделе приведены контактные данные лиц, проводящих исследование, и информация о том, где проводится это исследование.

Места учебы

Германия
- - Munich, Германия, 81377
    - Рекрутинг
    - Department of Urology, LMU University Hospital Munich
    - Контакт:
      
      Can Aydogdu, MD
      
      Номер телефона: +49 89 4400 0
      
      Электронная почта: can.aydogdu@med.uni-muenchen.de

Критерии участия

Исследователи ищут людей, которые соответствуют определенному описанию, называемому критериям приемлемости. Некоторыми примерами этих критериев являются общее состояние здоровья человека или предшествующее лечение.

Критерии приемлемости

Возраст, подходящий для обучения

18 лет и старше (Взрослый, Пожилой взрослый)

Принимает здоровых добровольцев

Нет

Полы, имеющие право на обучение

Все

Метод выборки

Невероятностная выборка

Исследуемая популяция

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.

Описание

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

Учебный план

В этом разделе представлена подробная информация о плане исследования, в том числе о том, как планируется исследование и что оно измеряет.

Как устроено исследование?

Детали дизайна

Наблюдательные модели: COHORT
Временные перспективы: PROSPECTIVE

Что измеряет исследование?

Первичные показатели результатов

Мера результата	Временное ограничение
Event Free Survival (EFS) Временное ограничение: From treatment initiation up to 36 months	From treatment initiation up to 36 months

Вторичные показатели результатов

Мера результата	Мера Описание	Временное ограничение
Pathologic Complete Response (pCR) Временное ограничение: At radical cystectomy		At radical cystectomy
Pathologic Downstaging Временное ограничение: 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) Временное ограничение: Up to 36 months after surgery	Time from curative surgery until recurrence or death.	Up to 36 months after surgery
Overall Survival (OS) Временное ограничение: 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 Временное ограничение: 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 Временное ограничение: 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 Временное ограничение: 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 Временное ограничение: 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

Соавторы и исследователи

Здесь вы найдете людей и организации, участвующие в этом исследовании.

Спонсор

LMU Klinikum

Даты записи исследования

Эти даты отслеживают ход отправки отчетов об исследованиях и сводных результатов на сайт ClinicalTrials.gov. Записи исследований и сообщаемые результаты проверяются Национальной медицинской библиотекой (NLM), чтобы убедиться, что они соответствуют определенным стандартам контроля качества, прежде чем публиковать их на общедоступном веб-сайте.

Изучение основных дат

Начало исследования (Действительный)

17 мая 2026 г.

Первичное завершение (Оцененный)

31 декабря 2026 г.

Завершение исследования (Оцененный)

31 мая 2029 г.

Даты регистрации исследования

Первый отправленный

17 мая 2026 г.

Впервые представлено, что соответствует критериям контроля качества

1 октября 2026 г.

Первый опубликованный (Действительный)

2 октября 2026 г.

Обновления учебных записей

Последнее опубликованное обновление (Действительный)