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

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 在美国有大约80万膀胱癌幸存者，使其成为第五大流行癌症。本研究 专注于最大的膀胱癌患者群体，79%的非肌层浸润性早期 癌根据目前的指南建议，这些患者接受经尿道内窥镜切除术 随后每3至6个月进行一次监测性膀胱镜检查， 每年的程序。膀胱镜检查需要通过膀胱镜直接检查膀胱，该膀胱镜插入到膀胱内。 患者的尿道。它可以是相当不舒服，因为它是在非镇静病人进行。尽管如此 患者的负担，高强度监测膀胱镜检查的好处缺乏高质量的数据。的 撰写指南的专家们认识到高强度监测的好处并不明确， 他说：“迫切需要研究来确定是否可以采用不太严格的随访方案 而不会显著影响这些患者的肿瘤结果。”用微创膀胱镜替代膀胱镜 尿检是这样一种不太严格的随访方案。初步数据显示， 膀胱癌监测（基于mRNA）和膀胱EpiCheck（DNA甲基化测试）可能取代膀胱镜检查 由于其高度的敏感性。然而，特异性为0.76和0.84，四分之一的测试 可能是假阳性，所以很多患者仍然要接受膀胱镜检查，以获得阳性结果。因此，纵向 在考虑将这些测试用于常规护理之前，需要比较数据。具体来说，我们需要 有证据表明，通过尿检进行的方案性监测大大减轻了监测的负担， 在不同的膀胱癌幸存者人群中，肿瘤学结局可接受。这里我们 将确定膀胱癌尿液检查可以在多大程度上减轻患者的监测负担。 我们提出了一个三个网站的随机2期试验，包括240例早期膀胱癌患者。后 研究入组时进行正常监测膀胱镜检查，患者将以1：1：1的比例随机分配至计划监测组 使用Xpert膀胱癌尿液检测、膀胱EpiCheck尿液检测或标准膀胱镜检查。我们将 (1)确定尿检组与对照组相比， 标准膀胱镜检查，（2）比较尿液检测组与标准组的短期安全性结果 第1年和第2年的膀胱镜检查，以及（3）估计后续较大非劣效性的重要可行性数据 效果比较试验。总之，我们将系统地研究监测的负担是否 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。如果膀胱癌尿检显著减轻负担 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， 与标准膀胱镜检查相比，尿液检测的程序性监测足够大， 用于肿瘤学结果。