Determining the clinical impact of gene expression testing in localized prostate cancer

确定基因表达检测对局限性前列腺癌的临床影响

• 批准号: 9979803
• 负责人: Todd M. Morgan
• 金额: $ 40.33万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-01 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9979803
• 关键词: Address; Biochemical; Biopsy; Brain Neoplasms; Cancer Control; Cancer Etiology; Cancer Patient; Categories; Clinical; Conduct Clinical Trials; Data; Decision Making; Development; Diagnosis; Discrimination; Disease; Erectile dysfunction; Evaluation; Failure; Future; Gene Expression; Genetic; Genomics; Goals; Grouping; Guidelines; Health Expenditures; Healthcare Systems; Incidence; Individual; Indolent; Longterm Follow-up; Magnetic Resonance Imaging; Malignant Neoplasms; Malignant neoplasm of pancreas; Malignant neoplasm of prostate; Methods; Michigan; Modeling; Morbidity - disease rate; Nature; Newly Diagnosed; Outcome; Pathologic; Patient Care; Patient risk; Patient-Focused Outcomes; Patients; Population; Prostatectomy; Prostatic Neoplasms; Quality of life; Radiation Oncology; Radical Prostatectomy; Randomized; Randomized Clinical Trials; Recommendation; Recurrence; Recurrent disease; Registries; Reporting; Research; Risk; Risk stratification; Shapes; Staging; Stratification; System; Testing; Time; Tissues; Treatment Failure; Treatment-Related Cancer; Tumor Biology; Ultrasonography; Urinary Incontinence; Urologic Surgical Procedures; Urology; Walking; Work; base; cancer care; clinical decision-making; clinical practice; clinical risk; clinically relevant; cohort; cost; expectation; follow-up; high risk; high risk men; improved; melanoma; men; overtreatment; personalized medicine; price lists; prospective; prostate cancer risk; randomized trial; targeted treatment; tumor; tumor progression; uptake; years lived with disability

The long-term goal of this project is to simultaneously decrease treatment-related morbidity from unnecessary over-treatment of men with localized prostate cancer (PCa) while curing more men by minimizing under- treatment of men with higher risk PCa. In this proposal we aim to determine if tissue based gene expression classifiers (GEC) can be utilized to improve both cancer control and quality of life (QOL) in men with localized PCa. This goal will be carried out through three specific aims. In Aim 1 we will develop a universal risk score that combines genetic, clinical, and pathologic variables in a manner that is agnostic to which of the three commercially available GEC tests used. This will be done through assembling a large cohort of men with targeted MRI/ultrasound fusion biopsies of the same prostate tumor focus and analyzing individual tumors with each of the three tests. We will then develop a conversion method aligning each GEC score with a new universal score, and we will apply this to a cohort of 1000 men with newly diagnosed prostate cancer followed in our statewide prospective registry. This data will be utilized to validate our recently developed clinical- genomic risk grouping system, broadening it to incorporate all GEC tests, and focusing it on appropriate stratification of favorable risk prostate cancer potentially suitable for active surveillance. We hypothesize that the universal integrated clinical-genomic risk groups will provide improved discrimination compared to standard clinical categories and will expand the pool of active surveillance-eligible patients. In Aim 2 we will conduct the first ever prospective randomized trial of the clinical utility and clinical impact of GEC testing in favorable risk localized prostate cancer, leveraging two statewide collaboratives containing over 60 urology and radiation oncology practices. Patients will be randomized to standard clinical risk stratification +/- GEC testing in order to determine the impact of testing on treatment decisions (active surveillance versus radical treatment), cancer control, and QOL. We hypothesize that GEC testing will decrease the use of primary therapy and increase QOL at 3 years, while maintaining rates of grade reclassification and biochemical recurrence at the same time point. Aim 3 seeks to determine the clinical impact of GEC testing on treatment failure and patient-reported QOL in men at high risk of recurrence post-prostatectomy. This aim leverages the recently accrued G-MINOR trial that randomized approximately 350 men at high risk of failure after prostatectomy to clinical risk stratification +/- GEC testing to assess decision making based on GEC testing. By extending the follow-up of this trial, we will determine how GEC testing impacts long-term tumor control and QOL. We hypothesize that GEC use in higher risk patients will provide more accurate risk stratification and targeted treatment decisions, leading to improved cancer control and QOL. This work has the potential to personalize treatment decision- making for PCa patients based on their tumor’s biology, allowing some men to avoid costly and toxic over- treatment while also decreasing the burden of recurrent disease from inappropriate under-treatment.

该项目的长期目标是同时减少与治疗相关的不必要的发病率 对患有局限性前列腺癌(PCA)的男性进行过度治疗，同时通过最小化不足治疗更多的男性- 前列腺癌高危男性的治疗。在这项建议中，我们的目标是确定基于组织的基因表达 分类器(GEC)可用于改善本地化男性癌症控制和生活质量(QOL) PCA。这一目标将通过三个具体目标来实现。在目标1中，我们将开发一个通用的风险评分 它结合了遗传、临床和病理变量，而这三种变量中的哪一种是不可知的 使用商业上可用的GEC测试。这将通过召集一大群男性和 同一前列腺肿瘤病灶的靶向MRI/超声融合活检并分析单个肿瘤与 三种测试中的每一种。然后，我们将开发一种转换方法，将每个GEC分数与新的 通用评分，我们将对1000名新诊断为前列腺癌的男性进行随访 在我们全州范围内的未来登记中。这些数据将被用于验证我们最近开发的临床- 基因组风险分组系统，将其扩大到包括所有GEC测试，并将重点放在适当的 前列腺癌的有利风险分层，可能适合于积极监测。我们假设 与标准相比，普遍整合的临床-基因组风险组将提供更好的鉴别力 临床分类，并将扩大符合积极监测条件的患者池。在目标2中，我们将进行 首次对风险有利的GEC检测的临床实用性和临床影响进行前瞻性随机试验 局限性前列腺癌，利用两个全州范围的合作项目，包含60多个泌尿外科和放射治疗 肿瘤学实践。患者将随机接受标准的临床风险分层+/-GEC测试，以便 确定检测对治疗决策的影响(积极监测与根治性治疗)、癌症 控制力和生活质量。我们假设GEC检测将减少初级治疗的使用，而增加 生活质量3年，同时保持分级再分类和生化复发率 指向。目的3旨在确定GEC检测对治疗失败和患者报告的临床影响 前列腺癌术后复发高危人群的生活质量。这一目标利用了最近积累的G小调 这项试验将大约350名前列腺癌术后失败风险较高的男性随机分为临床风险组 分层+/-GEC测试，以评估基于GEC测试的决策。通过延长以下项目的后续行动 在这项试验中，我们将确定GEC检测如何影响长期的肿瘤控制和生活质量。我们假设 在高危患者中使用GEC将提供更准确的风险分层和有针对性的治疗决定， 从而改善癌症控制和生活质量。这项工作有可能使治疗决策个性化- 根据肿瘤的生物学特性为前列腺癌患者做准备，使一些男性避免昂贵和有毒的过度 治疗的同时也减少了因不适当的治疗而复发的疾病的负担。