Tailored prostate cancer screening: addressing USPSTF priority research gaps in a racially-diverse study population

量身定制的前列腺癌筛查：解决 USPSTF 在种族多样化研究人群中的优先研究差距

基本信息

批准号：
10735739
负责人：
Marvin Epolian Langston
金额：
$ 68.02万
依托单位：
STANFORD UNIVERSITY
依托单位国家：
美国
项目类别：
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/10735739
关键词：
Address Adoption Age Archives Black race California Cancer Diagnostics Cancer Etiology Categories Cessation of life Clinical Cohort Studies Data Detection Diagnosis Economics Electronic Health Record Erectile dysfunction European Exposure to Frequencies Future Goals Health Health Care Costs Human Glandular Kallikrein 2 Integrated Health Care Systems Investigation Kininogenase Length Literature Malignant Neoplasms Malignant neoplasm of prostate Morbidity - disease rate PSA level PSA screening Phase Population Preventive care Prostate Prostate Cancer therapy Prostate-Specific Antigen Psyche structure Race Recommendation Relative Risks Research Priority Risk Running Sample Size Sampling Screening for Prostate Cancer Serum Specimen Testing Treatment Side Effects Uncertainty United States Preventative Services Task Force Variant base black men checkup examination clinical predictors clinically relevant cohort comorbidity cost design early screening empowerment evidence base follow-up high risk men high standard improved indexing member men mortality novel novel strategies older men overtreatment preservation prevent prostate cancer prevention prostate cancer risk racial diversity risk prediction risk stratification screening screening guidelines study population validation studies young man

项目摘要

ABSTRACT Screening for prostate cancer (PCa) is highly controversial, as accumulated evidence indicates that widespread, routine prostate-specific antigen (PSA)-based screening reduces PCa mortality but at the cost of significant over- diagnosis and over-treatment. PSA-based risk-stratified screening could capture much of the benefit of screening while greatly reducing over-diagnosis. This promising approach uses men’s baseline PSA values to inform their risk of future aggressive and/or fatal PCa and determine their frequency of further screening. Under this approach, men with high baseline age-specific total PSA levels receive more frequent screening and men with lower levels receive less frequent screening. This efficient approach is currently supported by at least three US advisory agencies, but not by several others, including most notably, the US Preventive Services Task Force. This agency recommends additional “validation studies” with “longer-term follow-up” before considering PSA- based risk-stratified screening. Additional data are also needed to optimize each of the components of PSA- based risk-stratified screening, including the: (1) age at which baseline PSA values should be obtained, (2) length of tailored re-screening intervals, (3) tailored age at screening cessation, (4) tailored strategies for Black men, as these men are at higher risk of aggressive and fatal PCa, yet remarkably under-represented in the screening literature, and (5) prostate-specific kallikreins used for screening, as kallikreins beyond total PSA have also been found to predict PCa risk and mortality and thus might help to optimize PSA-based risk-stratified screening. Therefore, to address each of these gaps, we propose to leverage data and serum specimens collected in the large racially-diverse Kaiser Permanente Northern California integrated health system, along with its long- running (over 5 decades), embedded Multiphasic Health Checkups cohort and nested case-cohort to: (1) evaluate the utility of initiating baseline PSA screening before age 50, (2) determine the optimal re-screening interval after a baseline PSA test, (3) identify populations of men at age 60 who might consider stopping screening, (4) explore whether Black men should initiate screening earlier and be screened more frequently than White men, and (5) evaluate whether adding other prostate-specific kallikreins to total PSA enhances prediction of clinically-relevant PCa. Our overall goal is to provide evidence for “smarter” or more nuanced PSA screening strategies to preserve or enhance the mortality benefits of PSA screening, while greatly minimizing its harms and costs.

抽象的前列腺癌 (PCa) 筛查极具争议性，因为积累的证据表明，前列腺癌 (PCa) 筛查广泛存在基于前列腺常规特异性抗原 (PSA) 的筛查可降低 PCa 死亡率，但代价是显着过度基于 PSA 的风险分层筛查可以从筛查中获益。同时大大减少过度诊断，这种有希望的方法使用男性的基线 PSA 值来告知他们。未来侵袭性和/或致命性前列腺癌的风险，并根据此确定进一步筛查的频率。方法中，基线年龄特定总 PSA 水平较高的男性接受更频繁的筛查，而患有较低水平的筛查频率较低，这种有效的方法目前得到至少三个美国的支持。咨询机构，但其他几个机构则没有，其中最著名的是美国预防服务工作组。该机构建议在考虑 PSA 之前进行额外的“验证研究”和“长期随访” 还需要额外的数据来优化 PSA 的每个组成部分。基于风险分层的筛查，包括：（1）应获得基线PSA值的年龄，（2）身长定制的重新筛查间隔，(3) 定制的停止筛查年龄，(4) 为黑人男性定制的策略，因为这些男性患侵袭性和致命性前列腺癌的风险较高，但在筛查中的代表性却明显不足文献，以及（5）用于筛查的前列腺特异性激肽释放酶，因为超出总 PSA 的激肽释放酶也已被发现可以预测 PCa 风险和死亡率，因此可能有助于优化基于 PSA 的风险分层筛查。因此，为了解决这些差距，我们建议利用收集的数据和血清样本北加州凯撒医疗机构 (Kaiser Permanente) 拥有庞大的种族多元化综合医疗系统，以及其长期运行（超过 5 年）、嵌入式多阶段健康检查队列和嵌套病例队列：(1) 评估 50 岁之前开始基线 PSA 筛查的效用，(2) 确定最佳的重新筛查基线 PSA 测试后的间隔，(3) 确定 60 岁可能考虑停止测试的男性群体筛查，（4）探讨黑人男性是否应该更早开始筛查并更频繁地进行筛查白人男性，以及 (5) 评估在总 PSA 中添加其他前列腺特异性激肽释放酶是否可以增强预测我们的总体目标是为“更智能”或更细致的 PSA 筛查提供证据。保持或提高 PSA 筛查的死亡率益处，同时大大减少其危害的策略和成本。