Modeling to Improve Prostate Cancer Outcomes Across Diverse Populations

 描述(申请人提供)：前列腺癌是男性最常见的癌症。在美国，每7名男性中就有1名在有生之年被诊断患有前列腺癌。找出方法 因此，减轻前列腺癌的负担是研究的重中之重。自从PSA检测的出现和广泛传播以来，前列腺癌的管理已经发生了巨大的变化。自20世纪90年代初以来，美国前列腺癌死亡率下降了近一半。为了使用疾病模型来解释这些死亡率趋势，成立了CISNET前列腺癌工作组(PWG)。CISNET PWG开发了前列腺癌自然病史、检测和生存的三个模型，并根据美国前列腺癌的趋势对它们进行了校准。结果表明，筛查和治疗的改变都降低了前列腺癌的死亡率。然而，必须调整政策，以限制与过度诊断和过度治疗相关的危害和成本。已经提出了不同的方法来做到这一点，但不可能都在前瞻性研究中进行调查。该应用程序的目标是利用和扩展CISNET PWG模型，以确定在限制危害和成本的同时提供最大收益的量身定做和有针对性的干预策略。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进筛查，以及我们是否可以通过明智地选择初级和次级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口和可能需要修改策略的国际癌症控制环境中。我们将通过具有图形用户界面的在线计算器为决策者提供模型访问。我们的具体目标是：目标1：确定积极的监测战略，在不增加进展为不可治愈的疾病或死亡的风险的情况下将患者负担降至最低。目标2：根据多基因风险和45岁时的基线PSA，开发针对高危男性的前列腺癌分层筛查方法。目的3：模型二次治疗策略，它们的影响，以及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口的癌症控制计划，并与英国和加勒比海地区的研究人员合作，为他们的人口和资源制定政策。目标6：开发在线计算器，以支持患者-医生的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筹资机会的宣布，涉及9个目标优先领域中的6个。我们在前列腺建模方面的累积专业知识、我们现有的模型以及我们与临床专家的密切联系，这些专家为模型验证和校准提供了大型、高质量的数据集，使我们能够为如何最好地应对和控制这种最常见的男性癌症的国内和国际对话做出独特贡献。

 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.