Department of Urology, Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Miami, FL, USA.
Division of Biostatistics, Department of Public Health Sciences, Sylvester Biostatistics and Bioinformatics Shared Resource, Miller School of Medicine, University of Miami, Miami, FL, USA.
Lancet. 2018 Jun 23;391(10139):2525-2536. doi: 10.1016/S0140-6736(18)30996-6.
Radical cystectomy is the surgical standard for invasive bladder cancer. Robot-assisted cystectomy has been proposed to provide similar oncological outcomes with lower morbidity. We aimed to compare progression-free survival in patients with bladder cancer treated with open cystectomy and robot-assisted cystectomy.
The RAZOR study is a randomised, open-label, non-inferiority, phase 3 trial done in 15 medical centres in the USA. Eligible participants (aged ≥18 years) had biopsy-proven clinical stage T1-T4, N0-N1, M0 bladder cancer or refractory carcinoma in situ. Individuals who had previously had open abdominal or pelvic surgery, or who had any pre-existing health conditions that would preclude safe initiation or maintenance of pneumoperitoneum were excluded. Patients were centrally assigned (1:1) via a web-based system, with block randomisation by institution, stratified by type of urinary diversion, clinical T stage, and Eastern Cooperative Oncology Group performance status, to receive robot-assisted radical cystectomy or open radical cystectomy with extracorporeal urinary diversion. Treatment allocation was only masked from pathologists. The primary endpoint was 2-year progression-free survival, with non-inferiority established if the lower bound of the one-sided 97·5% CI for the treatment difference (robotic cystectomy minus open cystectomy) was greater than -15 percentage points. The primary analysis was done in the per-protocol population. Safety was assessed in the same population. This trial is registered with ClinicalTrials.gov, number NCT01157676.
Between July 1, 2011, and Nov 18, 2014, 350 participants were randomly assigned to treatment. The intended treatment was robotic cystectomy in 176 patients and open cystectomy in 174 patients. 17 (10%) of 176 patients in the robotic cystectomy group did not have surgery and nine (5%) patients had a different surgery to that they were assigned. 21 (12%) of 174 patients in the open cystectomy group did not have surgery and one (1%) patient had robotic cystectomy instead of open cystectomy. Thus, 302 patients (150 in the robotic cystectomy group and 152 in the open cystectomy group) were included in the per-protocol analysis set. 2-year progression-free survival was 72·3% (95% CI 64·3 to 78·8) in the robotic cystectomy group and 71·6% (95% CI 63·6 to 78·2) in the open cystectomy group (difference 0·7%, 95% CI -9·6% to 10·9%; p=0·001), indicating non-inferiority of robotic cystectomy. Adverse events occurred in 101 (67%) of 150 patients in the robotic cystectomy group and 105 (69%) of 152 patients in the open cystectomy group. The most common adverse events were urinary tract infection (53 [35%] in the robotic cystectomy group vs 39 [26%] in the open cystectomy group) and postoperative ileus (33 [22%] in the robotic cystectomy group vs 31 [20%] in the open cystectomy group).
In patients with bladder cancer, robotic cystectomy was non-inferior to open cystectomy for 2-year progression-free survival. Increased adoption of robotic surgery in clinical practice should lead to future randomised trials to assess the true value of this surgical approach in patients with other cancer types.
National Institutes of Health National Cancer Institute.
根治性膀胱切除术是浸润性膀胱癌的手术标准。机器人辅助膀胱切除术被提议提供类似的肿瘤学结果，同时降低发病率。我们旨在比较接受开放性膀胱切除术和机器人辅助膀胱切除术治疗的膀胱癌患者的无进展生存率。
RAZOR 研究是在美国 15 个医疗中心进行的一项随机、开放标签、非劣效性、3 期试验。合格的参与者（年龄≥18 岁）有经活检证实的临床 T1-T4、N0-N1、M0 膀胱癌或难治性原位癌。以前接受过开放性腹部或骨盆手术的患者，或有任何会妨碍安全开始或维持气腹的预先存在的健康状况的患者被排除在外。患者通过一个基于网络的系统以 1:1 的比例进行中心分配，通过机构进行块随机化，按尿流改道类型、临床 T 分期和东部合作肿瘤学组表现状态分层，接受机器人辅助根治性膀胱切除术或开放性根治性膀胱切除术伴体外尿流改道。治疗分配仅对病理学家保密。主要终点是 2 年无进展生存率，如果治疗差异（机器人膀胱切除术减去开放性膀胱切除术）的单侧 97.5%CI 的下限大于-15 个百分点，则确定非劣效性。主要分析在方案人群中进行。安全性在同一人群中进行评估。该试验在 ClinicalTrials.gov 注册，编号为 NCT01157676。
2011 年 7 月 1 日至 2014 年 11 月 18 日期间，350 名参与者被随机分配到治疗组。176 名患者的预期治疗是机器人膀胱切除术，174 名患者的预期治疗是开放性膀胱切除术。机器人膀胱切除术组的 17 名（10%）患者未进行手术，9 名（5%）患者接受了与预期手术不同的手术。开放性膀胱切除术组的 21 名（12%）患者未进行手术，1 名（1%）患者接受了机器人膀胱切除术而不是开放性膀胱切除术。因此，302 名患者（机器人膀胱切除术组 150 名，开放性膀胱切除术组 152 名）被纳入方案分析集。机器人膀胱切除术组的 2 年无进展生存率为 72.3%（95%CI 64.3-78.8），开放性膀胱切除术组为 71.6%（95%CI 63.6-78.2）（差异 0.7%，95%CI-9.6%至 10.9%；p=0.001），表明机器人膀胱切除术具有非劣效性。机器人膀胱切除术组 150 名患者中有 101 名（67%）和开放性膀胱切除术组 152 名患者中有 105 名（69%）发生了不良事件。最常见的不良事件是尿路感染（机器人膀胱切除术组 53 例[35%]，开放性膀胱切除术组 39 例[26%]）和术后肠梗阻（机器人膀胱切除术组 33 例[22%]，开放性膀胱切除术组 31 例[20%]）。
在膀胱癌患者中，机器人膀胱切除术在 2 年无进展生存率方面与开放性膀胱切除术相比非劣效。机器人手术在临床实践中的广泛应用应导致未来的随机试验，以评估这种手术方法在其他癌症类型患者中的真正价值。
美国国立卫生研究院国家癌症研究所。
