Replacing Invasive Cystoscopy with Urine Testing for Non-muscle Invasive Bladder Cancer Surveillance

项目摘要 美国约有80万膀胱癌幸存者，使其成为第五大最常见的癌症。本研究 重点关注人群最大的膀胱癌患者，79%的患者早期无肌肉侵袭 癌症。根据目前的指南建议，这些患者接受经尿道内窥镜电切术。 其次是每隔3至6个月进行一次监视膀胱镜检查，使膀胱镜检查在100多万人中很常见 每年的程序。膀胱镜检查需要通过膀胱镜直接检查膀胱，膀胱镜被插入到 病人的尿路。它可能会相当不舒服，因为它是在未服用镇静剂的患者身上进行的。尽管如此 对于患者的负担，高强度监视膀胱镜检查的好处缺乏高质量的数据。这个 撰写指南的专家认识到了高强度监视的不明确好处，特别是 声明：“目前迫切需要进行研究，以确定是否可以采用不那么严格的后续治疗方案。 而不会对这些患者的肿瘤学结果产生重大影响。以更小的侵入性取代膀胱镜检查 尿检是这样一种不那么严格的后续治疗方案。初步数据显示，尿液测试Xpert 膀胱癌监测(基于mRNA)和膀胱表检查(DNA甲基化检测)可能取代膀胱镜检查 程序，鉴于其高度敏感性。然而，在特异性为0.76和0.84的情况下，多达四分之一的测试 可能是假阳性，所以许多患者仍然需要接受膀胱镜检查才能呈阳性。因此，纵向的 在考虑将这些测试用于常规护理之前，需要比较数据。具体地说，我们需要 有证据表明，通过尿检进行程序性监测显著减少了对儿童的监测负担 并且在不同人群的膀胱癌幸存者中具有可接受的肿瘤学结果。在这里，我们 将确定通过膀胱癌尿检可以在多大程度上减轻患者的监测负担。 我们提出了一项包括240名早期膀胱癌患者的三点随机第二阶段试验。之后 在研究开始时，患者将随机进行1：1：1的程序性监测 使用Xpert膀胱癌尿检、膀胱镜尿检或标准膀胱镜检查。我们会 (1)确定尿液检测部门的监测负担是否显著低于 标准膀胱镜检查，(2)比较尿检臂和标准膀胱镜检查的短期安全结果 一年和两年的膀胱镜检查，以及(3)评估重要的可行性数据，以确定随后的大范围非劣势 比较有效性试验。综上所述，我们将系统研究监控负担是否 用尿液代替侵入性膀胱镜检查可以改善膀胱癌幸存者的膀胱镜检查 测试，最终提高他们的生活质量。如果膀胱癌患者进行尿检，会大大减轻负担 ，我们的数据将为随后的比较有效性试验提供强有力的理由 使用尿液检测的程序化监控与大到可以供电的标准膀胱镜检查 肿瘤学结果。

Project Summary There are ~800,000 bladder cancer survivors in the US, making it the fifth most prevalent cancer. This study focuses on the largest group of patients with bladder cancer, the 79% with non-muscle invasive early-stage cancer. Per current guideline recommendations, these patients undergo transurethral endoscopic resection followed by surveillance cystoscopy every 3 to 6 months, making cystoscopy common with over a million procedures per year. Cystoscopy entails direct inspection of the bladder via a cystoscope that is inserted into a patient's urethra. It can be quite uncomfortable as it is performed in non-sedated patients. In spite of this burden on patients, high-quality data on the benefits of high-intensity surveillance cystoscopy are lacking. The experts writing the guidelines recognized the unclear benefit of high-intensity surveillance and specifically stated: “There is an urgent need for studies to determine if less stringent follow-up regimens can be employed without significantly affecting oncologic outcomes in these patients.” Replacing cystoscopy with less invasive urine testing is such a less stringent follow-up regimen. Preliminary data show that the urine tests Xpert Bladder Cancer Monitor (mRNA-based) and Bladder EpiCheck (DNA methylation test) may replace cystoscopy procedures, given their high sensitivities. However, with a specificity 0.76 and 0.84, up to one out of four tests may be false positive, so many patients still have to undergo cystoscopy for positive tests. Thus, longitudinal comparative data are needed before these tests can be considered for routine care. Specifically, we need evidence that programmatic surveillance with urine tests significantly decreases the burden of surveillance for patients and has acceptable oncologic outcomes in diverse populations of bladder cancer survivors. Here, we will define the extent to which patients' burden of surveillance can be reduced with bladder cancer urine tests. We propose a three-site randomized phase 2 trial including 240 patients with early-stage bladder cancer. After a normal surveillance cystoscopy at study entry, patients will be randomized 1:1:1 to programmatic surveillance with the Xpert bladder cancer urine test, the Bladder EpiCheck urine test, or standard cystoscopy. We will (1) determine whether burden of surveillance is significantly decreased in the urine testing arms versus standard cystoscopy, (2) compare short-term safety outcomes in the urine testing arms versus standard cystoscopy at 1 and 2 years, and (3) estimate important feasibility data for a subsequent large non-inferiority comparative effectiveness trial. In summary, we will systematically study whether the burden of surveillance cystoscopy can be improved among bladder cancer survivors by replacing invasive cystoscopy with urine testing, ultimately improving their quality of life. If bladder cancer urine tests significantly decrease the burden of surveillance, our data will provide a strong justification for a subsequent comparative effectiveness trial of programmatic surveillance with urine testing versus standard cystoscopy that is large enough to be powered for oncologic outcomes.