Open vs Robot-Assisted Radical Cystectomy: A Randomized Trial

描述（由申请人提供）：开放性根治性膀胱癌（ORC）目前是肌肉浸润性膀胱癌的金标准治疗。虽然它与足够的生存结局相关，但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，手术机器人已经应用于膀胱癌患者。据推测，机器人辅助根治性膀胱切除术（RARC）可显著改善围手术期结局和功能恢复时间，而不会影响肿瘤学有效性。如果RARC可能导致有利的围手术期和功能结局，如果其导致肿瘤有效性和控制低于传统ORC，则其在膀胱癌手术治疗中的常规使用可能是不合理的。此外，RARC在市场上被认为上级传统手术，但没有通过随机试验进行系统的比较有效性评估。到目前为止，大多数RARC的结局研究要么是病例系列报告，要么是比较有效性的研究，具有重大的方法学局限性。需要比较RARC与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的使命保持一致，追求研究和应用知识，延长健康的生活，减少疾病和残疾的负担，我们计划进行一项3期多机构随机临床试验，比较膀胱癌患者的长期肿瘤和功能结果之间的ARC和ORC，严格评估的影响，ARC相比，ORC。我们将测量2年无进展生存期、总生存期、患者报告的围手术期发病率以及功能独立性、生活质量和成本结局的性能相关指标。我们的入组目标为总共320例患者，这将充分支持使用非劣效性设计（预定义的非劣效性界值为15%）进行研究。13个三级护理学术中心积极参与我们的提案，验证了进行我们拟议试验的重要性。这项研究的结果对于确定RARC与ORC相比的比较有效性至关重要，并可能改变膀胱癌患者手术方法的护理标准。参与机构沿着的根治性细胞切除术数量极高，且患者参与NIH资助的随机对照试验的经验丰富，这使得患者参与的机会和意愿显著增加。在我们努力实现医疗资源的有效利用时，至关重要的是我们要评估新技术的真正有效性，并确定其他领域的改进是否证明了更高的前期成本是合理的。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。 公共卫生相关性：与传统的开放手术相比，手术机器人的使用有可能显着改善膀胱癌患者的恢复并降低发病率。然而，机器人技术与陡峭的学习曲线相关，被认为更昂贵，并且对长期癌症相关结果具有不确定性。卫生资源的优化利用是当前社会面临的一个重要问题。我们提出的临床试验将是第一个明确的比较有效性研究，比较机器人和开放式手术方法在长期癌症结局，恢复，围手术期发病率，成本和生活质量方面的差异，这将有助于影响膀胱癌患者未来的手术方法。

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.