Optimizing prostate cancer care: integrating risks, benefits, and patient experiences in the new era of molecular imaging

项目概要/摘要 前列腺癌的分子成像革命正在进行中。为了克服长期存在的局限性， 前列腺癌分期，最近已经批准了几种正电子发射断层扫描（PET）扫描， 基于提高诊断准确性的证据，快速整合到临床护理中。但 广泛PET成像的后果是未知的。这是因为这些测试的批准是 基于诊断准确性的提高，替代终点，而不是患者受益的直接证据。通过 早期发现小的癌症部位，PET成像可以引入一系列的效应--既有积极的， 阴性-这可能因患者而异。PET成像可以提高生存率， 在一个子集中，转移性癌症的症状，但也可能增加治疗毒性，心理 别人的负担和代价。目前，没有任何信息可以帮助指导患者或利益相关者， 考虑到这些权衡。为了减少这些不确定性，我们的目标是开发一个决策模型， 考虑了PET成像在多个维度上的影响。为了让这个模型更好，我们将生成真实的- 世界各地的证据来源多样。在目标一中，我们将对大型， 评估PET成像有效性的全国代表性数据库，重点关注 全身治疗的影像学启动、进展为难治性疾病和费用之间的关系。在aim中 第二，我们将测量PET成像对患者报告的结局指标的纵向影响， 心理影响（焦虑和不确定性）和健康相关的生活质量。为了获得更深的视角 关于患者的测试体验，我们还将在较小的 患者的子集，并整合定量和定性来源的结果。在第三项研究中，我们 将结合目标1和目标2的输入，构建基于个体的状态转换微观仿真模型 检查PET成像使用的常见场景。这些模型的输出将包括以下估计数： 有效性，以及可能与更大或更小程度的 利或弊。这项研究的结果将使患者，供应商和其他前列腺癌利益相关者 关于PET成像的潜在短期和长期影响的实用新信息。如果成功， 这种评估有效性的方法将适用于其它类似的分子成像模式， 将很快进入临床护理的基础上提高诊断准确性的替代终点，但没有 长期临床疗效的证据。

PROJECT SUMMARY/ABSTRACT A molecular imaging revolution is underway in prostate cancer. To overcome longstanding limitations in prostate cancer staging, several positron-emission tomography (PET) scans have recently been approved and rapidly integrated into clinical care based on evidence of improved diagnostic accuracy. However, the consequences of widespread PET imaging are unknown. This is because the approvals of these tests are based on improved diagnostic accuracy, a surrogate endpoint, rather than direct evidence of patient benefit. By finding small sites of cancer earlier, PET imaging could introduce a cascade of effects—both positive and negative—that could vary from patient to patient. PET imaging could lead to improved survival and fewer symptoms from metastatic cancer in a subset, but could also increase treatment toxicity, psychological burdens, and costs in others. Currently, no information is available to help guide patients or stakeholders when considering these tradeoffs. To reduce these uncertainties, our goal is to develop a decision model that considers the effects of PET imaging across multiple dimensions. To inform this model, we will generate real- world evidence from a diversity of sources. In aim one, we will conduct complementary analyses of large, nationally representative databases to evaluate the effectiveness of PET imaging, focusing on the associations between imaging initiation of systemic therapy, progression to hormone-refractory disease, and costs. In aim two, we will measure the longitudinal impact of PET imaging on patient-reported outcome measures relating to psychological effects (anxiety and uncertainty) and health-related quality of life. To gain a deeper perspective about patient experiences with testing we will also conduct longitudinal qualitative interviews among a smaller subset of patients and integrate the findings from quantitative and qualitative sources. In the third study aim we will incorporate inputs from Aims 1 and 2 to construct individual-based state-transition microsimulation models examining common scenarios for PET imaging use. The outputs from these models will include estimates of effectiveness, as well as patient characteristics that may be associated with greater or lesser degrees of benefit or harm. The results of this study will equip patients, providers, and other prostate cancer stakeholders with practical, new information about the potential short and long-term effects of PET imaging. If successful, this approach for evaluating effectiveness will be applicable to other similar molecular imaging modalities that will soon enter clinical care on the basis of surrogate endpoints of improved diagnostic accuracy, but without evidence of long-term clinical efficacy.