MULTIPLEXED PROTEIN BIOMARKER-BASED ASSAY FOR THE DETECTION OF BLADDER CANCER

用于检测膀胱癌的多重蛋白质生物标志物检测

• 批准号: 10307878
• 负责人: Charles J Rosser
• 金额: $ 72.61万
• 依托单位: CEDARS-SINAI MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-05-01 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10307878
• 关键词: Adjuvant; Age; Algorithms; BCG Live; Biological Assay; Biological Markers; Bladder; Blood; Cancer Detection; Cancer Patient; Caring; Clinic; Clinical; Cohort Studies; Cost Analysis; Cost Savings; Cost utility; Costs and Benefits; Cystectomy; Cystoscopy; Cytology; Data; Diagnosis; Diagnostic; Disease; Effectiveness; Ensure; Evaluation; Excision; Funding; Gender; General Population; Gold; Guidelines; Health Care Costs; Hematuria; Image; Immunoassay; Institution; Invasive Lesion; Laboratories; Life; Malignant neoplasm of urinary bladder; Manuscripts; Measures; Medicine; Methodology; Methods; Microscopic; Molecular Profiling; Muscle; Newly Diagnosed; Outpatients; Parents; Patient Care; Patient Rights; Patients; Performance; Prediction of Response to Therapy; Predictive Value; Prospective cohort; Publishing; Recording of previous events; Recurrence; Research; Residual Tumors; Retrospective cohort; Risk; Sampling; Schedule; Specificity; Survival Rate; Technology; Technology Transfer; Testing; Time; Tobacco; Translating; Translations; Transurethral Resection; Tumor stage; Urine; Validation; Weight; base; cancer biomarkers; cancer diagnosis; clinically relevant; cohort; cost; cost effective; cost effectiveness; detection assay; diagnostic assay; high risk; improved; intravesical; markov model; multiplex assay; muscle invasive bladder cancer; patient response; patient stratification; predicting response; predictive modeling; preservation; prospective; protein biomarkers; response; risk stratification; treatment response; tumor; tumorigenesis; urinary

Project Summary/Abstract Background Microscopic hematuria (blood in urine) may occur in up to 10% of the general population and results in costly evaluation to ensure it is of no consequence, i.e., no bladder cancer (BCa) is present since hematuria is typically the initial sign of BCa. Furthermore, 75% of patients with newly diagnosed BCa have non- muscle-invasive disease (NMIBC), which has a very high recurrence rate (>70%). Because of this, it is recommended that the patients have adjuvant intravesical bacillus Calmette-Guerin (BCG) instillation to reduce this risk. Despite BCG treatment, up to 50% of patients fail to respond and 20% progress to muscle invasive bladder cancer (MIBC) mandating more radical treatment (i.e., cystectomy - removal of the urinary bladder). Moreover, the delay in radical treatment can negatively impact survival rates, hence, a test that could predict treatment response to intravesical BCG, ensuring the right patient, gets the right treatment at the right time is urgently required. To date, no such test is available. There exists an unmet clinical need for reliable biomarkers to a) ‘rule out’ which patients with microscopic hematuria do not require further evaluation and b) predict which patients will respond to BCG. Hypothesis Our central hypothesis is that a molecular profile exists that is specifically associated with BCa that a) can be utilized to indicate the presence of BCa in non-invasively obtained urine samples and b) can be utilized to predict response to BCG. This hypothesis will be tested by completing the following Specific Aims: 1) To validate the multiplex immunoassay for BCa detection in subjects presenting with microscopic hematuria, 2) To evaluate the cost benefit, cost utility and cost effectiveness of the multiplex immunoassay in subjects with hematuria and a history of BCa on tumor surveillance and 3) To validate prospectively the urine-based multiplex immunoassay to predict BCG response in subjects with intermediate/high risk NMIBC. Significance This research will open the door for improving on the non-invasive methods for detecting BCa and predicting treatment response as such it will have a marked impact on patient care. Methodology Our group has developed and tested a multiplex immunoassay towards a BCa signature with extremely encouraging results in subjects evaluated for gross hematuria and a history of BCa on tumor surveillance. In the current proposal, we now seek to test the multiplex assay in two additional independent cohorts: intermediate/high-risk patients (AUA microscopic hematuria guidelines 2020) presenting with microscopic hematuria for early BCa detection and patients with intermediate/high risk NMIBC treated with intravesical BCG to predict treatment response. Furthermore, we will generate Markov models and using data collected from the parent R01 to assess cost benefit, cost utility and cost effectiveness of the multiplex immunoassay. Expected Results The validation of the multiplex immunoassay will reduce the need to subject large numbers of patients who do not have BCa to frequent, uncomfortable and expensive cystoscopic examinations. Specifically, we would anticipate a reduction in the number of cystoscopies/year by 500,000, which would translate into cost savings of $225 million/year.

项目总结/摘要 显微镜下血尿（尿中带血）可能发生在高达10%的普通人群中， 导致昂贵的评估，以确保它是没有后果的，即，没有膀胱癌（BCa），因为 血尿通常是BCa的初始体征。此外，75%的新诊断BCa患者没有 肌肉浸润性疾病（NMIBC），其具有非常高的复发率（>70%）。正因为如此， 建议患者辅助膀胱内卡介苗（BCG）灌注，以减少 这个风险。尽管BCG治疗，高达50%的患者没有反应，20%的进展为肌肉侵入性 膀胱癌（MIBC）要求更彻底的治疗（即，膀胱切除术-切除膀胱）。 此外，根治性治疗的延迟会对生存率产生负面影响，因此，可以预测 膀胱内BCG的治疗反应，确保正确的患者，在正确的时间得到正确的治疗， 迫切需要。到目前为止，还没有这样的测试。存在对可靠生物标志物的未满足的临床需求 a）“排除”哪些显微镜下血尿患者不需要进一步评估，以及B）预测哪些 患者对BCG有反应。假设我们的中心假设是存在一种分子谱， a）可用于非侵入性地指示BCa在 获得的尿样和B）可用于预测对BCG的反应。这一假设将由以下人员进行检验： 完成以下具体目的：1）验证BCa检测的多重免疫测定法， 以显微镜下血尿为表现的受试者，2）评价成本效益、成本效用和成本 多重免疫测定法在血尿和BCa肿瘤史受试者中的有效性 前瞻性验证尿免疫多重检测法预测BCG反应 中/高风险NMIBC受试者。意义本研究将为改进 用于检测BCa和预测治疗反应的非侵入性方法本身将具有 对病人护理有明显影响。我们的小组已经开发并测试了一种多重免疫测定法， BCa标志在肉眼血尿评估的受试者中具有非常令人鼓舞的结果， 肿瘤监测中的BCa病史。在目前的建议中，我们现在试图在两个实验室中测试多重测定法。 其他独立队列：中/高风险患者（AUA显微镜下血尿指南2020） 出现显微镜下血尿以进行早期BCa检测和中/高危NMIBC患者 用膀胱内BCG治疗以预测治疗反应。此外，我们将生成马尔可夫模型， 使用从母公司R 01收集的数据，评估成本效益、成本效用和成本效益， 多重免疫测定预期结果多重免疫分析的验证将减少 使大量没有BCa的患者接受频繁、不舒服和昂贵的治疗， 膀胱镜检查。具体而言，我们预计膀胱镜检查次数/年将减少 50万美元，相当于每年节省费用2.25亿美元。