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
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 670
- 试验地点
- 5
- 主要终点
- Recurrence-free survival
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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-
- •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.
排除标准
- •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.
研究组 & 干预措施
Active Surveillance
Participants assigned to this arm will undergo active surveillance after complete transurethral resection of bladder tumor. No adjuvant intravesical chemotherapy will be given. Surveillance will include scheduled cystoscopy, urine cytology, urine-based liquid biopsy testing, and other assessments according to the study protocol. Further diagnostic evaluation or treatment will be performed if recurrence or progression is suspected or confirmed.
干预措施: Active Surveillance (Other)
Adjuvant Intravesical Chemotherapy
Participants assigned to this arm will receive one year of adjuvant intravesical chemotherapy after complete transurethral resection of bladder tumor. The preferred agent is gemcitabine; mitomycin C or epirubicin may be used as protocol-allowed alternatives when gemcitabine is unavailable, contraindicated, or not routinely used at the participating center. The planned agent will be specified before randomization. Treatment will consist of an induction course of weekly intravesical instillations followed by maintenance instillations for up to 12 months, according to the study protocol.
干预措施: Adjuvant Intravesical Chemotherapy (Drug)
结局指标
主要结局
Recurrence-free survival
时间窗: Up to 24 months after randomization
Recurrence-free survival is defined as the time from randomization to the first histologically confirmed intravesical recurrence or death from any cause, whichever occurs first.
次要结局
- High-grade recurrence-free survival(Frame: Up to 24 months after randomization)
- Progression-free survival(Up to 24 months after randomization)
- Overall Survival(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(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(Baseline, Weeks 6, 12, 24, 36, and 48)
- EuroQol 5-Dimension 5-Level Questionnaire (EQ-5D-5L) Scores(Baseline, Weeks 6, 12, 24, 36, and 48)