Modeling to Improve Prostate Cancer Outcomes Across Diverse Populations

 描述（由申请人提供）：前列腺癌是男性中最常见的癌症。在美国，七分之一的男性在一生中会被诊断为前列腺癌。确定如何 因此，减少前列腺癌的负担是一项首要的研究重点。前列腺癌的管理已经发生了巨大的变化，因为PSA测试的出现和广泛传播。自20世纪90年代初以来，美国的前列腺癌死亡率下降了近一半。CISNET前列腺工作组（PWG）的成立是为了使用疾病模型来解释这些死亡率趋势。CISNET PWG开发了三种前列腺癌自然史、检测和生存模型，并根据美国前列腺癌趋势对其进行了校准。结果表明，筛查和治疗的变化都降低了前列腺癌的死亡率。然而，政策必须量身定制，以限制与过度诊断和过度治疗相关的伤害和成本。已经提出了不同的方法来实现这一点，但不能在前瞻性研究中进行研究。本应用程序的目的是利用和扩展CISNET PWG模型，以确定量身定制的有针对性的干预策略，提供最大的好处，同时限制伤害和成本。我们将确定我们是否可以通过使用新的分层方法进一步改善筛查，以及我们是否可以通过明智地选择主要和次要治疗来安全地限制过度治疗的危害。这些方法将应用于美国人群和可能需要修改策略的国际癌症控制环境。我们将为决策者提供通过图形用户界面的在线计算器访问模型。我们的具体目标是：目标1：确定积极的监测策略，最大限度地减少患者负担，而不增加进展为不可治愈疾病或死亡的风险。目标2：基于多基因风险和45岁时的基线PSA，开发针对高危男性的前列腺癌筛查分层方法。目标3：模型二级治疗策略，其影响，并对人群前列腺癌控制的影响。目的4：确定是否可以通过分层筛查和治疗策略减少前列腺癌死亡率的种族差异。目标5：模块化模型，以评估非美国人群的癌症控制计划，并与英国和加勒比地区的研究人员合作，为其人口和资源制定政策。目标六：开发在线计算器，以支持患者-医生决策和政策制定者对PSA筛查和治疗局限性前列腺癌的审议。这些目标高度响应了供资机会公告，涉及9个目标优先领域中的6个。我们在前列腺建模方面积累的专业知识，我们现有的模型，以及我们与临床专家的密切联系，这些专家提供了用于模型验证和校准的大型高质量数据集，使我们能够为国家和国际对话做出独特的贡献，讨论如何最好地解决和控制这种最常见的男性癌症。

 DESCRIPTION (provided by applicant): Prostate cancer is the most common cancer in men. In the US, 1 in 7 men will experience a prostate cancer diagnosis in his lifetime. Identifying ways to reduce the burden of prostate cancer is therefore a top research priority. Management of prostate cancer has changed dramatically since the advent and widespread dissemination of the PSA test. Since the early 1990s, prostate cancer mortality in the US has dropped by almost half. The CISNET Prostate Working Group (PWG) was formed to use disease modeling to explain these mortality trends. The CISNET PWG has developed three models of prostate cancer natural history, detection, and survival and calibrated them against US prostate cancer trends. Results indicate that both screening and treatment changes have reduced prostate cancer deaths. However, policies must be tailored to limit harms and costs associated with overdiagnosis and overtreatment. Different approaches for doing this have been proposed but cannot all be investigated in prospective studies. The objective of this application is to utilize and extend the CISNET PWG models to identify tailored and targeted intervention strategies that offer the most benefit while limiting harms and costs. We will determine whether we can improve screening further by using novel stratification approaches and also whether we can safely limit harms of overtreatment by judicious choices of primary and secondary therapies. These approaches will be applied in the US population and in international cancer control settings that may require modified strategies. We will provide decision makers with model access via online calculators with graphical user interfaces. Our specific aims are: Aim 1: Identify active surveillance strategies that minimize patient burden without increasing risks of progression to non-curable disease or death. Aim 2: Develop stratified approaches to prostate cancer screening that target high-risk men based on polygenic risk and baseline PSA at age 45. Aim 3: Model secondary treatment strategies, their impact, and implications for population prostate cancer control. Aim 4: Determine whether racial disparities in prostate cancer mortality can be reduced by using stratified screening and treatment strategies. Aim 5: Modularize models to evaluate cancer control programs in non-US populations and collaborate with investigators in the UK and the Caribbean to develop policies for their populations and resources. Aim 6: Develop online calculators to support patient-physician decisions and policymaker deliberations about PSA screening and treatment for localized prostate cancer. These aims are highly responsive to the funding opportunity announcement, addressing 6 of the 9 targeted priority areas. Our cumulative expertise in prostate modeling, our existing models, and our close ties with clinical experts who provide access to large, high-quality datasets for model validation and calibration position us well to uniquely contribute to the national and international dialogue about how best to address and control this most common cancer in men.