VI-RADS指导下的非肌层浸润性膀胱癌经光动力经尿道切除术与白光传统及二次切除术的‘无切除’随机试验方案

欧洲泌尿学会（EAU）指南建议对非肌层浸润性膀胱癌（NMIBC）患者进行第二次经尿道切除术（Re-TURBT），以应对初次切除后可能的分期不足和/或疾病持续。然而，在许多情况下，这可能是不必要的、潜在有害且昂贵的，属于过度治疗。’无切除’试验旨在结合膀胱影像报告与数据系统（VI-RADS）的术前分期准确性和光动力诊断（PDD）的术中增强能力，克服初次TURBT的缺陷，从而可能重新定义Re-TURBT的适应症。为期4年在单中心进行的非劣效性、IV期、开放标签、随机对照试验，比例为1:1。主要终点是两组间短期膀胱癌复发率，以评估对于术前被分类为VI-RADS 1和/或2分（即极低和低可能性肌层浸润性膀胱癌，MIBC）患者，是否可以在避免Re-TURBT的情况下，进行初次PDD-TURBT。次要终点包括中长期的膀胱癌复发和进展（i-ii）、生活质量（iii）以及健康经济成本效益分析（iv）。所有患者将接受膀胱的多参数磁共振成像，确定VI-RADS评分。计划在3年内招募327名符合中高风险NMIBC标准、符合Re-TURBT指征的患者。患者将随机（1:1）分配到常规护理（包括初次白光TURBT及随后的二次白光Re-TURBT）或试验组（初次PDD-TURBT，省略Re-TURBT）。两组均接受风险调整的辅助膀胱内治疗和随访。主要指标为在4.5个月内（首次随访膀胱镜检查时）检测到的膀胱癌早期复发比例。次要指标为4.5个月后检测到的晚期复发及/或进展比例。此外，将模拟患者终生的膀胱癌生活质量变化，并进行短期成本效益分析，包括避免Re-TURBT的增量成本和长远的品质调整生命年（QALY）成本效益分析，利用两组治疗的2年临床结果驱动终生模型。ClinicalTrial.gov编号：NCT05962541；EudraCT编号：2023-507307-64-00。

A second transurethral resection of bladder tumour (Re-TURBT) is recommended by European Association of Urology (EAU) Guidelines on non-muscle-invasive bladder cancers (NMIBCs) due to the risk of understaging and/or persistent disease following the primary resection. However, in many cases this may be unnecessary, potentially harmful, and significantly expensive constituting overtreatment. The CUT-less trial aims to combine the preoperative staging accuracy of Vesical Imaging-Reporting and Data System (VI-RADS) and the intraoperative enhanced ability of photodynamic diagnosis (PDD) to overcome the primary TURBT pitfalls thus potentially re-defining criteria for Re-TURBT indications.Single-centre, non-inferiority, phase IV, open-label, randomised controlled trial with 1:1 ratio.The primary endpoint is short-term BC recurrence between the study arms to assess whether patients preoperatively categorised as VI-RADS Score 1 and/or Score 2 (i.e., very-low and low likelihood of MIBC) could safely avoid Re-TURBT by undergoing primary PDD-TURBT. Secondary endpoints include mid- and long-term BC recurrences and progression (i-ii). Also, health-related quality of life (HRQoL) outcomes (iii) and health-economic cost-benefit analysis (iv) will be performed.All patients will undergo preoperative Multiparametric Magnetic Resonance Imaging of the bladder with VI-RADS score determination. A total of 327 patients with intermediate-/high-risk NMIBCs, candidate for Re-TURBT according to EAU Guidelines, will be enrolled over a 3-year period. Participants will be randomised (1:1 ratio) to either standard of care (SoC), comprising primary white-light (WL) TURBT followed by second WL Re-TURBT; or the Experimental arm, comprising primary PDD-TURBT and omitting Re-TURBT. Both groups will receive adjuvant intravesical therapy and surveillance according to risk-adjusted schedules. Measure of the primary outcome will be the relative proportion of BC recurrences between the SoC and Experimental arms within 4.5 months (i.e., any 'early' recurrence detected at first follow-up cystoscopy). Secondary outcomes measures will be the relative proportion of late BC recurrences and/or BC progression detected after 4.5 months follow-up. Additionally, we will compute the HRQoL variation from NMIBC questionnaires modelled over a patient lifetime horizon and the health-economic analyses including a short-term cost-benefit assessment of incremental costs per Re-TURBT avoided and a longer-term cost-utility per quality-adjusted life year gained using 2-year clinical outcomes to drive a lifetime model across the two arms of treatment.ClinicalTrial.gov identifier (ID): NCT05962541; European Union Drug Regulating Authorities Clinical Trials Database (EudraCT) ID: 2023-507307-64-00.