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

用尿液检测代替侵入性膀胱镜检查进行非肌肉侵入性膀胱癌监测

• 批准号: 10559724
• 负责人: Florian R Schroeck
• 金额: $ 58.39万
• 依托单位: VETERANS EDUCATION/RES/ASSN/NORTH/NE
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-01 至 2028-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10559724
• 关键词: Affect; Anxiety; Biological; Bladder; Cancer Survivor; Cystoscopes; Cystoscopy; DNA Methylation; Data; Dropout; Enrollment; Evaluation; Excision; Goals; Guidelines; Incidence; Intervention; Malignant Neoplasms; Malignant neoplasm of urinary bladder; Measures; Messenger RNA; Modeling; Monitor; Outcome; Patients; Pattern; Population Heterogeneity; Procedures; Quality of life; Randomized; Recommendation; Recurrence; Recurrent Malignant Neoplasm; Regimen; Safety; Site; Specificity; Testing; Time; Urethra; Urine; Visual; Work; Writing; analog; arm; cancer recurrence; comparative; comparative effectiveness trial; efficacy evaluation; follow-up; improved; interest; methylation testing; non-muscle invasive bladder cancer; patient oriented; phase II trial; primary outcome; routine care; safety and feasibility; safety outcomes; screening; secondary outcome; sex; tumor progression; urinary; validation studies; Affect; Anxiety; Biological; Bladder; Cancer Survivor; Cystoscopes; Cystoscopy; DNA Methylation; Data; Dropout; Enrollment; Evaluation; Excision; Goals; Guidelines; Incidence; Intervention; Malignant Neoplasms; Malignant neoplasm of urinary bladder; Measures; Messenger RNA; Modeling; Monitor; Outcome; Patients; Pattern; Population Heterogeneity; Procedures; Quality of life; Randomized; Recommendation; Recurrence; Recurrent Malignant Neoplasm; Regimen; Safety; Site; Specificity; Testing; Time; Urethra; Urine; Visual; Work; Writing; analog; arm; cancer recurrence; comparative; comparative effectiveness trial; efficacy evaluation; follow-up; improved; interest; methylation testing; non-muscle invasive bladder cancer; patient oriented; phase II trial; primary outcome; routine care; safety and feasibility; safety outcomes; screening; secondary outcome; sex; tumor progression; urinary; validation studies

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.

项目摘要 美国有约800,000个膀胱癌存活，使其成为第五大癌症。这项研究 重点是最大的膀胱癌患者组，有79％的非肌肉侵入性早期阶段 癌症。根据当前的指南建议，这些患者接受了尿道尿道内窥镜切除术 然后每3至6个月进行一次监视膀胱镜检查，使膀胱镜检查与超过一百万 每年程序。膀胱镜需要通过插入膀胱镜进行直接检查膀胱 病人的尿道。由于在非服装患者中进行，因此可能会非常不舒服。尽管如此 对患者的负担，缺乏有关高强度监测膀胱镜检查益处的高质量数据。 撰写准则的专家认识到高强度监视的不清楚好处 指出：“迫切需要研究来确定是否可以雇用较少严格的随访方案 在这些患者中没有显着影响肿瘤学结局。 尿液测试是一种不太严格的随访方案。初步数据显示尿液测试XPERT 膀胱癌监测仪（基于mRNA）和膀胱叶片（DNA甲基化测试）可能会取代膀胱镜检查 鉴于其高灵敏度，程序。但是，特异性为0.76和0.84，最多四个测试中有一个 可能是假阳性的，因此许多患者仍必须进行膀胱镜检查以进行阳性测试。那，纵向 在考虑常规护理之前，需要进行比较数据。具体来说，我们需要 证据表明，通过尿液测试进行程序性监测大大减轻了监视负担 患者并具有可接受的肿瘤学结局，在Bladeder癌症存活的潜水员种群中。在这里，我们 将确定通过膀胱癌尿液检查可以减少患者监测的程度。 我们提出了一项三个位置随机2期试验，包括240例早期膀胱癌患者。后 在研究条目时进行的正常监视膀胱镜检查，患者将被随机分为1：1：1。 通过Xpert膀胱癌尿液测试，膀胱尿液测试或标准膀胱镜检查。我们将 （1）确定尿液测试中的监视负担是否显着减轻 标准膀胱镜检查，（2）比较尿液测试手臂中的短期安全结果与标准 1和2年的膀胱镜检查，以及（3）估计随后的大型非效率的重要可行性数据 比较有效性试验。总而言之，我们将系统地研究监视的燃烧 膀胱镜可以通过用尿液代替侵入性膀胱镜来改善膀胱癌存活中的膀胱镜 测试，最终改善其生活质量。如果膀胱癌尿液测试显着降低燃烧 监视，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 通过尿液测试与标准膀胱镜检查的程序化监测，足够大的膀胱镜检查 用于肿瘤学结果。