Open vs Robot-Assisted Radical Cystectomy: A Randomized Trial

描述（由申请人提供）：开放式根治性膀胱切除术（ORC）是目前治疗肌肉浸润性膀胱癌的金标准。虽然它与足够的生存结果相关，但它也与相当长的恢复时间和术后发病率相关。为了减少手术的侵入性，手术机器人已被应用于膀胱癌患者。据推测，机器人辅助根治性膀胱切除术（RARC）在不影响肿瘤疗效的情况下显著改善围手术期预后和功能恢复时间。如果RARC可以获得良好的围手术期和功能预后，那么如果RARC在肿瘤疗效和控制方面不如传统ORC，那么RARC在膀胱癌手术治疗中的常规应用可能是不合理的。此外，在没有通过随机试验进行系统的比较效果评估的情况下，RARC被宣传为优于传统手术。迄今为止，RARC的大多数结果研究要么是病例系列报告，要么是比较有效性研究，方法上存在主要局限性。需要比较RARC和ORC有效性的3期前瞻性随机试验来验证这一假设。为了与NIH追求研究和应用知识以延长健康生命和减少疾病和残疾负担的使命保持一致，我们计划开展一项多机构随机临床试验，比较RARC和ORC对膀胱癌患者的长期肿瘤学和功能结果，以严格评估RARC与ORC的影响。我们将测量每组的2年无进展生存期、总生存期、患者报告的围手术期发病率和功能独立性、生活质量和成本结果的表现相关指标。我们的累积目标是总共320名患者，使用非劣效性设计，预定义的非劣效性裕度为15%，足以为研究提供足够的动力。13个三级医疗学术中心积极参与我们的提案，验证了开展我们提议的试验的重要性。这项研究的结果对于确定RARC与ORC的比较效果至关重要，并可能改变膀胱癌患者手术入路的护理标准。在每一个参与的机构中都进行了大量的根治性膀胱切除术，并且在nih资助的随机对照试验中积累了丰富的经验，这大大增加了患者积累的机会和参与的意愿。在我们努力实现医疗保健资源的有效利用时，评估新技术的真正有效性并确定在其他领域的改进是否证明前期成本较高是合理的，这一点至关重要。在市场力量决定护理标准之前，有机会收集随机的前瞻性数据，比较RARC和ORC。

DESCRIPTION (provided by applicant): Open Radical Cystectomy (ORC) is currently the gold standard treatment for muscle-invasive bladder cancer. While it is associated with adequate survival outcomes, it is also associated with considerable recovery time and postoperative morbidity. With the intent of making the surgery less invasive, the use of surgical robot has been applied in patients with bladder cancer. It has been hypothesized that Robotic- Assisted Radical Cystectomy (RARC) significantly improves perioperative outcomes and time to functional recovery without compromising on the oncologic effectiveness. If RARC presumably results in favorable perioperative and functional outcomes, its routine use in surgical treatment of bladder cancer may not be justifiable if it results in inferior oncologic effectiveness and control compared to traditional ORC. Moreover, RARC is being marketed as superior to the traditional operation without systematic comparative effectiveness evaluations through randomized trials. To date, most outcome studies of RARC are either case series reports or comparative effectiveness studies with major methodological limitations. Phase 3 prospective randomized trials comparing the effectiveness of RARC to ORC are needed to validate this hypothesis. In keeping with NIH's mission to pursue research and apply knowledge that extends healthy life and reduces the burdens of illness and disability, we plan on conducting a phase 3 multi-institutional randomized clinical trial comparing long term oncologic and functional outcomes between RARC and ORC for bladder cancer patients to rigorously evaluate the impact of RARC compared to ORC. We will measure 2-year progression free survival, overall survival, perioperative morbidity patient reported and performance related measures of functional independence, quality of life and cost outcomes in each group. Our accrual goal of a total of 320 patients will adequately power the study using a non inferiority design with a predefined non inferiority margin of 15%. The importance of conducting our proposed trial is validated by the active participation of 13 tertiary care academic centers in our proposal. The results from this study will be critical to determining the comparative effectiveness of RARC compared with ORC and potentially change the standard of care in the surgical approach for patients with bladder cancer. The exceedingly high volume of radical cystectomies performed at each of the participating institutions along with the wealth of experience accruing patients to NIH-funded randomized controlled trials lends itself to significantly higher chances of patient accrual and willingness to participate. As we strive toward efficient utilization of healthcare resources, it is critical that we evaluate the true effectiveness of new technologies and determine whether the higher upfront costs are justified by improvements in other areas. There is a window of opportunity to gather randomized, prospective data, comparing RARC to ORC before the forces of the marketplace determine the standard of care. PUBLIC HEALTH RELEVANCE: The use of surgical robot has the potential to significantly improve recovery and decrease morbidity in patients with bladder cancer compared to the traditional open surgery. However, the robotic technology is associated with a steep learning curve, perceived as more expensive with uncertainty about long term cancer related outcomes. Optimal utilization of health care resources is a critical issue faced by our society at present. Our proposed clinical trial will be the first definitive comparative effectiveness study comparing robotic and open approach to surgery with regards to long term cancer outcomes, recovery, perioperative morbidity, costs and quality of life that will help influence future surgical approaches in patients with bladder cancer.