Active Surveillance Versus Adjuvant Intravesical Chemotherapy in Liquid Biopsy-Defined Low-Shedding Intermediate-Risk NMIBC

Официальное название

A Prospective, Multicenter, Randomized, Open-Label, Non-Inferiority Trial of Active Surveillance Versus Adjuvant Intravesical Chemotherapy After Complete Transurethral Resection in Patients With Preoperative Liquid Biopsy-Negative, Intermediate-Risk Non-Muscle-Invasive Bladder Cancer

Обзор

This study will evaluate whether adjuvant intravesical chemotherapy can be safely omitted under active surveillance after complete transurethral resection in selected patients with EAU intermediate-risk non-muscle-invasive bladder cancer. Patients with intermediate-risk non-muscle-invasive bladder cancer are commonly treated with transurethral resection followed by adjuvant intravesical chemotherapy to reduce the risk of recurrence. However, not all patients may derive the same benefit from additional intravesical treatment. Some tumors may have a low-shedding phenotype, meaning that they show no detectable tumor-associated signals in urine despite the presence of visible bladder tumors. In this study, preoperative urine-based liquid biopsy will be used to identify patients with a low-shedding profile. This profile is defined by negative results across urine cytology, NMP22, urinary DNA methylation, and urinary tumor DNA testing before transurethral resection. Eligible patients with EAU intermediate-risk non-muscle-invasive bladder cancer, a negative preoperative urine-based liquid biopsy profile, and complete tumor resection will be randomly assigned to active surveillance or standard adjuvant intravesical chemotherapy. The study will compare recurrence-free survival between the two groups and assess whether active surveillance can avoid immediate intravesical chemotherapy without compromising oncologic safety. Secondary outcomes will include high-grade recurrence, disease progression, need for subsequent bladder cancer treatment, safety, patient-reported outcomes.

Вмешательства

• Другое Active Surveillance
  Participants assigned to active surveillance will not receive adjuvant intravesical chemotherapy after complete transurethral resection of bladder tumor. They will undergo scheduled follow-up assessments, including cystoscopy, urine cytology, urine-based liquid biopsy testing, imaging when clinically indicated, and other evaluations according to the study protocol. Further diagnostic evaluation or treatment will be initiated if recurrence or progression is suspected or confirmed.
• Препарат Adjuvant Intravesical Chemotherapy
  Participants assigned to this intervention will receive one year of adjuvant intravesical chemotherapy after complete transurethral resection of bladder tumor. Gemcitabine is the preferred protocol-specified agent. Mitomycin C or epirubicin may be used as protocol-allowed alternatives when gemcitabine is unavailable, contraindicated, or not routinely used at the participating center. Treatment will include an induction course followed by maintenance intravesical instillations for up to 12 months

Первичные конечные точки

• Recurrence-free survival [Срок оценки: Up to 24 months after randomization]

Вторичные конечные точки (6)

• High-grade recurrence-free survival [Срок оценки: Frame: Up to 24 months after randomization]
• Progression-free survival [Срок оценки: Up to 24 months after randomization]
• Overall Survival [Срок оценки: Up to 24 months after randomization]
• European Organization for Research and Treatment of Cancer-Quality of Life Questionnaire Core-30 items (EORTC-QLQ-C30) Scores [Срок оценки: Baseline, Weeks 6, 12, 24, 36, and 48]
• European Organization for Research and Treatment of Cancer-Quality of Life Questionnaire for Non muscle Invasive Bladder Cancer (EORTC-QLQ-NMIBC24) Scores [Срок оценки: Baseline, Weeks 6, 12, 24, 36, and 48]
• EuroQol 5-Dimension 5-Level Questionnaire (EQ-5D-5L) Scores [Срок оценки: Baseline, Weeks 6, 12, 24, 36, and 48]

Критерии участия

Критерии включения

• Age ≥18 years.
• Histologically confirmed urothelial carcinoma of the urinary bladder, including tumors with divergent differentiation, provided that the urothelial carcinoma component accounts for >50% of the tumor
• Non-muscle-invasive bladder cancer classified as intermediate-risk according to the 2021 European Association of Urology (EAU) NMIBC prognostic risk-group definition. Intermediate-risk disease is defined as NMIBC without concomitant carcinoma in situ that does not meet the criteria for the EAU low-, high-, or very-high-risk groups.
• Complete transurethral resection of all visible bladder tumors performed within 6 weeks before randomization, with no macroscopically visible residual disease.
• Negative multi-urinary liquid biopsy results after complete TURBT and before randomization.
• Eastern Cooperative Oncology Group performance status of 0-2.
• Adequate clinical condition to undergo protocol-specified intravesical therapy, cystoscopic surveillance, and study-related procedures.
• Ability to understand the study requirements and provide written informed consent.

Критерии исключения

• EAU low-risk, high-risk, or very-high-risk NMIBC.
• Any current or previous concomitant carcinoma in situ associated with the qualifying tumor episode.
• Muscle-invasive bladder cancer, locally advanced urothelial carcinoma, lymph-node involvement, or metastatic urothelial carcinoma.

Incomplete TURBT, macroscopically visible residual tumor, or inability to achieve complete endoscopic resection before randomization.

• Urothelial carcinoma involving the prostatic stroma or prostatic ducts, or carcinoma in situ of the prostatic urethra.
• Severe lower urinary tract dysfunction, bladder capacity considered insufficient for intravesical treatment, or another clinically significant urological condition that may interfere with treatment or outcome assessment.
• Another active malignancy requiring systemic treatment or likely to interfere with the assessment of study endpoints, except adequately treated non-melanoma skin cancer, localized prostate cancer under surveillance, or another malignancy with a negligible risk of recurrence, as determined by the investigator.
• Pregnant or breastfeeding women.
• Any serious uncontrolled medical, psychiatric, or social condition that, in the investigator's judgment, would compromise participant safety, protocol adherence, or interpretation of study results.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 5 центров

• Daqing Oil General Hopital — Daqing
• Nanchang Second People's Hospital — Nanchang
• The Second Hospital of Tianjin Medical University — Тяньцзинь
• General Hospital of Tianjin Medical University — Тяньцзинь
• Tianjin Hospital — Тяньцзинь

Идентификаторы

NCT: NCT07749924 · Truce-LB04

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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