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

• 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
• 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

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.

摘要 筛查前列腺癌（PCa）是非常有争议的，因为积累的证据表明，广泛， 常规的前列腺特异性抗原（PSA）筛查可降低PCa死亡率，但代价是显著的 诊断和过度治疗。基于PSA的风险分层筛查可以获得筛查的大部分益处 同时大大减少过度诊断。这种有前途的方法使用男性的基线PSA值来告知他们的 未来侵袭性和/或致命性PCa的风险，并确定其进一步筛查的频率。根据本 采用这种方法，基线年龄特异性总PSA水平高的男性接受更频繁的筛查， 较低级别的人接受检查的频率较低。这种有效的方法目前得到至少三个美国国家的支持。 咨询机构，但不是由其他几个，包括最值得注意的是，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"- 基于风险分层筛选。还需要更多的数据来优化PSA的每个组成部分- 基于风险分层的筛选，包括：（1）应获得基线PSA值的年龄，（2）身高 量身定制的再筛查间隔，（3）量身定制的筛查停止年龄，（4）为黑人男性量身定制的策略， 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明显不足。 文献，和（5）用于筛选的前列腺特异性激肽释放酶，因为总PSA以外的激肽释放酶也已被 发现PSA可以预测PCa的风险和死亡率，因此可能有助于优化基于PSA的风险分层筛查。 因此，为了解决这些差距中的每一个，我们建议利用在 大型种族多元化的凯撒永久北方加州综合卫生系统，沿着其长期， 运行（超过50年），嵌入式多相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）确定最佳的再筛查 基线PSA检测后的间隔时间，（3）确定60岁时可能考虑停药的男性人群 筛查，（4）探讨黑人男性是否应该更早开始筛查，并比男性更频繁地进行筛查。 白色男性，和（5）评估是否增加其他前列腺特异性激肽释放酶的总PSA增强预测 临床相关前列腺癌我们的总体目标是为“更智能”或更细致入微的PSA筛查提供证据 保持或提高PSA筛查的死亡率益处，同时最大限度地减少其危害的策略 和成本。