A Pilot, Single-centre, Randomized, 5-year, Parallel-group, Superiority Trial to Compare Re-resection of High-grade T1 Bladder Urothelial Carcinoma to no Re-resection for Improving Progression Free Survival
试验速览
- 阶段
- 早期 1 期
- 状态
- 终止
- 入组人数
- 2
- 试验地点
- 1
- 主要终点
- 5 year Progression Free Survival
研究概览
简要总结
The investigators would like to compare the progression free survival, overall survival, quality of life, and safety outcomes of patients receiving versus not receiving a 2nd transurethral resection of bladder tumor.
详细描述
Background: Bladder cancer (BCa) is the 4th and 12th most common malignancies by incidence in Canadian men and women, respectively. In Canada, the lifetime probability of developing BCa is 1 in 27 men and 1 in 84 women. Urologists use a transurethral resection of bladder tumor (TURBT) to diagnose and stage patients with non-muscle invasive bladder cancer (NMIBC). While the value of repeat TURBT is not questioned for incomplete endoscopic resections, retrospective studies have suggested value in repeat resection for high grade T1 (T1HG) tumors even if they are completely resected, typically done within 6 weeks of the initial resection. Repeat TURBT for T1HG BCa has been touted to detect understaged tumors, remove occult residual disease, provide prognostic value and improve subsequent bladder therapy. To date, there is a paucity of high quality level-1 evidence validating repeat TURBT for T1HG compared to a single TURBT for improved long term disease specific outcomes.
Research Question: Among patients with T1HG BCa with completely resected tumor, is repeat TURBT superior to single TURBT for improving 53-year progression free survival (PFS), defined as >/=T2 local disease or lymph node disease/distant metastasis? Study Design: The RESECT trial is designed as a pilot, single-centre, 2-arm parallel-group, superiority randomized trial, with random permuted blocks (lengths of 4 or 6) and balanced allocation (1:1), conducted at the University Health Network.
Patient Population: Adult patients with completely resected T1HG bladder urothelial carcinoma are eligible to participate. Patients with either lymph node/distant metastases at presentation, variant histology, those that had their initial resection performed outside of a study centre, or patients with severe comorbidities are excluded.
Intervention: Repeat TURBT (experimental) versus T1HG standard of care (active control).
Outcomes: The primary outcome is the difference between the two intervention arms with regards to PFS over 5-years of follow-up. Secondary outcomes are the difference between the two intervention arms in: (i) clinical measures; (ii) survival measures; (iii) perioperative safety measures; and (iv) quality of life (QOL) questionnaires.
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 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Complete initial resection by a BCa-focused urologic oncologist; mandatory bladder detrusor muscle in the initial TURBT specimen and complete visible resection documented by the surgeon/OR staff by intra-operative photography.
- •Urothelial carcinoma as the predominant histology as determined by genitourinary specific pathologist (e.g. small (<50%) components of small cell, squamous cell or adenocarcinoma are allowable).
- •Able and willing to consent.
- •≥18 years old: BCa is primarily a disease of the elderly, thus we have elected to include healthy octogenarian/nonagenarian patients. Additionally, since a TURBT can be performed under general or spinal anesthesia, we feel that including these patients is acceptable.
排除标准
- •Lymph node or distant metastases at initial presentation - determined on standard BCa staging evaluation with a CT-urogram of the abdomen/pelvis and/or a preoperative chest x-ray demonstrating pulmonary metastases.
- •Extensive NMIBC disease warranting immediate cystectomy.
- •Variant histology (not urothelial carcinoma) - ie. micropapillary, plasmacytoid, nested or sarcomatoid variants.
- •No muscularis propria (inadequate bladder staging) present in the initial TURBT specimen.
- •Initial TURBT demonstrating T1HG disease performed outside of study centre - as per study protocol, quality control of surgical performance for this trial requires the TURBT to be performed by an experienced BCa-dedicated surgeon.
- •Patients with severe comorbidities, including but not limited to: (i) previous stroke with persistent cognitive, motor, etc deficits; (ii) recent (<6 months) myocardial infarction or current unstable angina; (iii) liver cirrhosis; (iv) severe chronic obstructive pulmonary disease (COPD)/respiratory disease. Patients must be suitable candidates for either spinal or general anesthesia.
- •Pregnancy or lactation.
研究组 & 干预措施
re-TURBT
Patients in this arm will receive a 2nd TURBT within 4-6 weeks of initial TURBT
干预措施: re-TURBT (Procedure)
6 BCG instillations
Patients in this arm will not receive a 2nd TURBT, but will receive 6 instillations of BCG.
干预措施: 6 weeks BCG instillation (Drug)
结局指标
主要结局
5 year Progression Free Survival
时间窗: 5 years
次要结局
- Survival Measures - These include disease specific survival and overall survival as measured over time from intervention to 5-years post-intervention.(5 years)
- Perioperative Safety Measures - These include rate of major complications as defined by the Clavien-Dindo classification as grade 3, 4, and 5.(5 years)
- Mean Change of Patient FACT BI Scores - This includes prospective collection with a validated BCa HRQOL instruments performed at each patient visit.(5 years)
- Clinical Measures - These include recurrence free survival (in the bladder), time to cystectomy, and metastases-free survival as measured over time from intervention to 5-years post-intervention.(5 years)