Urinary Biomarkers in the Detection of Urothelial Carcinoma of the Bladder
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- Change in urinary biomarker value from baseline following removal of bladder tumor
研究概览
简要总结
To assess the persistence of bladder cancer-specific biomarkers in urine collected pre-operatively, in resected cancer tissue, and in urine collected post-operatively. A panel of sensitive and specific bladder cancer biomarkers will be used to establish a signature of disease in pre-operative patients with a positive diagnosis for bladder cancer by current standard of care (e.g., in-office cystoscopy, OR cystoscopy). The specificity of these markers will be assessed, as well as the degree of non-specific signal attributable to other sources of biomolecules, by analyzing resected tumor tissue for the same biomarkers. Finally, post-operative urine will be assessed for the presence of these markers. To the extent this biomarker panel can be determined to be specific and sensitive, it may serve as an indicator of the degree to which the surgical intervention successfully eradicated the underlying disease. The investigators also aim to assess the stability of a biomarker signature in urine but evaluating several patient specimens over various time points throughout the day.
详细描述
Current standard of care in non-muscle invasive bladder cancer (NMIBC) relies on pathologic confirmation of negative margins as well as repeat transurethral resection. National Comprehensive Cancer Network (NCCN) and American Urological Association (AUA) guidelines specify a regular schedule of continued examination by cystoscopy and cytology to monitor the patient for the recurrence of disease.
Physicians Choice Laboratory Services (PCLS) is validating a panel of biomarkers isolated from voided urine for their combined ability to reliably detect the presence of transformed cell populations. These markers include somatic mutations in a number of oncogenes that have been well established as important etiologic factors in the development of bladder cancer in the scientific and clinical literature. In addition, regional hypermethylation of the genome is evaluated, as is the presence or absence of specific proteins involved in the disease state. Through measurement of these biomarkers using next generation sequencing and immunoassays, PCLS has been able to establish both the analytical and clinical validity of these markers in diagnosing disease. The statistical correlation of these biomarkers with the presence of transitional cell carcinoma has resulted in the ability to define a distinct disease signature indicative of disease in preliminary studies. The current study aims to expand upon these findings in an effort to offer physicians an additional tool with which to manage bladder cancer.
Hypothesis: Bladder cancer biomarkers will be elevated in preoperative and intraoperative urine specimens with direct correlation to the intact lesion(s), but will diminish significantly or disappear in urine specimens post-operatively with as a function of completion of resection. Further, the persistence of disease-specific biomarkers in urine post-operatively may correlate with the risk of recurrence or progression.
Biomarker levels will be determined from pre-, intra- and post-operative urine specimens, as well as from resected bladder tissue and will be statistically compared for changes that correlate with presence or absence of visible disease. Biomarkers from tissue samples will be quantified and compared with urine sample values.
The specific aims of the current proposal are to:
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Suspected or confirmed urothelial type bladder cancer
- •Scheduled for a transurethral resection of bladder tumor (TURBT) or cystectomy
排除标准
- •Less than 18 years of age
- •Known concurrent upper urinary tract disease
- •History of bladder or prostate radiation
- •Patients who are unwilling or unable to give consent
结局指标
主要结局
Change in urinary biomarker value from baseline following removal of bladder tumor
时间窗: An average of 1 month after surgery
Urinary biomarkers will be assessed pre-operatively from voided specimens. One month post-operatively, voided urine will again be assessed for changes in the level of urinary biomarker. DNA will be isolated from tissue or urine using commercially available validated kits. DNA will be quantified by standard procedures and analyzed for somatic mutation by targeted resequencing of selected regions of the genome. Specific gene targets include TP53, FGFR3, CDKN2A, TERT, and PIK3CA. Hypermethylation analysis will be conducted by bisulfite conversion of isolated DNA and sequencing to determine degree of methylation of specific CpG islands. CpG islands located in the promoter regions of OTX1, TWIST1 and ONECUT2 will be analyzed. Levels of Cystatin B will be assessed by quantitative immunoassay directly from urine.
次要结局
- Change in urinary biomarker value throughout the day(One day)
研究者
Kristen Scarpato
Assistant Professor
Vanderbilt University