Non-inferiority, Phase IV, Open-label, Randomized Controlled Trial of primary Photodynamic Trans-urethral Resection of Bladder Tumors (PDD-TURBT) versus conventional white-light TURBT plus Repeated-TURBT (Re-TURBT) in Non-Muscle Invasive Bladder Cancers (NMIBCs) candidate for second look and resection
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 258
- 试验地点
- 1
- 主要终点
- The relative proportions of patients with early BCa recurrence detected during first follow-up cystoscopy will be compared between the experimental and the standard of care arms. Given the different timetable pathway of the two arms under investigation, early BCa recurrence is defined in the experimental arm as any BCa recurrence at 3-months from primary PDD-TURBT while at 3-months from WL Re-TURBT in the standard of care arm.
研究概览
简要总结
To leverage our expertise in Bladder Cancer (BCa)intraoperative Trans-Uretrhal Resection of Bladder Tumor (TURBT), optical imaging enhancement by photodynamic (PDD)-guided resection, and clinical practice shift to improve the therapeutic algorithm and personalization of Non-muscle Invasive Bladder Cancers (NMIBCs). We aim to provide the highest level of evidence for re-defining European Association of Urology (EAU) Guidelines selecting criteria among NMIBCs who could safely avoid unjustified and unnecessary secondary resection (Re-TURBT) procedures. We intend to demonstrate how our experimental multidisciplinary approach will be not oncological inferior to the current standard of care algorithm thus justifying a paradigmatic shift towards a potentially more sustainable and cost-effective patient-tailored surgical approach in NMIBCs candidate for second look and resection (Re-TURBT). To this purpose, in a homogeneous cohort of pre-operative selected patients, we will determine the proportion of early BCa recurrences (i.e., within 4.5 months follow-up) in those NMIBC treated by standard of care (i.e., TURBT followed by Re-TURBT) compared to our novel algorithm proposal (i.e., primary PDD-TURBT followed by no Re-TURBT).
入排标准
- 年龄范围
- 18 years 至 65+ years（65+ Years, 18-64 Years）
- 接受健康志愿者
- 否
入选标准
- •Female and Male patients at least 18 years old referred for clinical suspicion of primary or recurrent BCa who have been advised to undergo TURBT.
- •Patients with a TUR-confirmed diagnosis of NMIBC and candidate for second look and resection (Re-TURBT) according to EAU Guidelines
- •No imaging evidence (i.e., mpMRI/VI-RADS score 1 or 2) of muscle-invasive, locally advanced, or metastatic BCa (i.e., only confirmed CIS, Ta, T1, N0, M0 will be considered eligible).
- •Patients who never received adjuvant Bacillus of Calmette-Guérin (BCG) immunotherapy (i.e., BCG naïve patients) for previous BCa history
- •Fit to undergo all procedures listed in protocol
- •Able to provide written informed consent
排除标准
- •Contraindication to TURBT and/or Re-TURBT
- •Initial TURBT diagnosis of Muscle-Invasive Bladder Cancer (MIBC, i.e., T2) or locally advanced BCa (i.e., T3-T4).
- •Preoperative evidence of metastatic disease (i.e., cN1 – N3 and/or cM1).
- •Visual evidence of low-risk NMIBC (solitary tumor and/or < 1 cm) before initial TURBT.
- •Visual evidence of MIBC on preliminary cystoscopy (i.e., non-papillary or sessile mass attached directly by its base without a stalk).
- •TURBT diagnosis of NMIBCs not eligible for Re-TURBT according to EAU Guidelines (i.e., Ta-LG; Ta-HG with detrusor muscle in the specimen; primary CIS)
- •Concomitant Upper tract (kidney or ureteric) tumours on imaging
- •Contraindication to adjuvant intravesical BCG immunotherapy
- •Unfit to undergo any procedures listed in protocol
结局指标
主要结局
The relative proportions of patients with early BCa recurrence detected during first follow-up cystoscopy will be compared between the experimental and the standard of care arms. Given the different timetable pathway of the two arms under investigation, early BCa recurrence is defined in the experimental arm as any BCa recurrence at 3-months from primary PDD-TURBT while at 3-months from WL Re-TURBT in the standard of care arm.
The relative proportions of patients with early BCa recurrence detected during first follow-up cystoscopy will be compared between the experimental and the standard of care arms. Given the different timetable pathway of the two arms under investigation, early BCa recurrence is defined in the experimental arm as any BCa recurrence at 3-months from primary PDD-TURBT while at 3-months from WL Re-TURBT in the standard of care arm.
次要结局
- The relative proportions of patient with late BCa recurrences (i.e., detected after 4.5 months follow-up) between the experimental and the standard of care arms.
- Time to late BCa recurrences (i.e., late disease-free interval), defined as first recurrence (including progression to muscle-invasive disease, distant metastases, and death due to bladder cancer) in patients without an early recurrence who had follow-up after 4.5 months (landmark analysis). Patients still alive without recurrence will be censored at the last follow-up. The time will be censored at death and/or radical cystectomy in the absence of recurrence (competing risk).
- The relative proportions of patient with progression to MIBC over follow-up between the experimental and the standard of care arms.
- Time to progression to MIBC (i.e., progression-free interval) defined as the time from randomization to first increase to BCa stage T2 or higher or distant metastases. Patients still alive without progression will be censored at the last follow-up. The time will be censored upon death and/or radical cystectomy before progression (competing risks).
- Standardized mean difference of total in-hospital cost and informal costs between the experimental and the standard of care arms. We will model costs and health state changes over a patient lifetime to estimate the incremental cost per Re-TURBT avoided, QALYs and costs to the NHS. This will be based on the updated version of the existing National Institute of Health Research (NIHR) HTA economic model using 2-year data from within the trial.
- Health related quality of life (HRQoL) from the administered questionnaires will be compared at three years between the experimental and the standard of care arms. Subsequently, these outcomes will be modelled over a patient lifetime time horizon using trial data.
研究者
Dr Francesco Del Giudice
Scientific
Universita' Degli Studi Di Roma La Sapienza