A Superiority Trial to Compare Re-resection of High-grade T1 Bladder Urothelial Carcinoma to no Re-resection for Improving Progression Free Survival

Titre officiel

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

Sommaire:

Les chercheurs veulent comparer la survie sans progression, la survie globale, la qualité de vie et l’innocuité chez des patients atteints d’une tumeur de la vessie soumis à une deuxième résection transurétrale par rapport à ceux qui n’y sont pas soumis

Description de l'essai

Primary Outcome:

  • 5 year Progression Free Survival
Secondary Outcome:
  • 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.
  • Survival Measures - These include disease specific survival and overall survival as measured over time from intervention to 5-years post-intervention.
  • Perioperative Safety Measures - These include rate of major complications as defined by the Clavien-Dindo classification as grade 3, 4, and 5.
  • Mean Change of Patient FACT BI Scores - This includes prospective collection with a validated BCa HRQOL instruments performed at each patient visit.
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 tumour (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) tumours 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 tumours, 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 tumour, 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.

Randomization: Randomization will occur at the central coordinating site using a computer-generated randomization schedule and random permuted blocks (of lengths 4 or 6). The allocation sequence will be implemented using sequentially numbered, opaque, sealed envelopes.

Blinding: Neither participants nor treating physicians will be blinded to treatment allocation. The research/data analyst team will be blinded as will the radiologists that assess surveillance imaging.

Sample Size: To test feasibility, a sample of 18 cases in 1 year is expected. Analysis: Proportional outcomes will be analyzed with Chi-square or Fisher's exact test and continuous variables will be analyzed with Student's t-test. Time to event outcomes will be analyzed using log-rank tests on Kaplan-Meier estimates, followed by adjusted Cox proportional-hazard models. Continuous variables with differences between two time periods will be analyzed suing an analysis of covariance, with baseline values and centre adjusted for as covariates. Continuous variable outcomes with values over multiple time periods will be analyzed using repeated measures analysis of covariance.

Follow-Up: In addition to baseline assessment, each participant will be followed up at 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 48, 60 months after the intervention with cystoscopic evaluation, and assessment of disease progression and QOL. Surveillance imaging will be every 6 months for the 5-year follow-up.

Voir cet essai sur ClinicalTrials.gov

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