Population Modeling of Bladder Cancer Detection and Control

摘要 膀胱癌是美国第二大最常见的泌尿生殖系统恶性肿瘤，约有 每年新增8万例，死亡17700人。它是一组不同的疾病，范围从 一般不会危及生命但需要长期治疗的局部可治疗的浅表肿瘤， 到需要多模式侵入性治疗且远端转移风险较高的晚期疾病 和死亡。它是美国第九大最昂贵的癌症，也是每名确诊患者中最昂贵的 治疗癌症的费用很高。膀胱癌的危险因素广泛地包括化学和环境因素。 摄取或发现的暴露，如吸烟和化学致癌物 工作场所，以及遗传异常和慢性膀胱炎。膀胱癌的预后 在过去的二十年里保持了相对稳定。然而，机会比比皆是，改善 膀胱癌的预防、检测和治疗。新的生物标志物的出现，以及新的 治疗，包括免疫疗法(检查点抑制剂)、基因疗法和抗体药物 在接下来的几年里，共轭可能会产生巨大的影响。膀胱癌易受人口模型的影响 因为它有很高的发病率、死亡率和成本，很可能可以通过减少吸烟和毒素来预防。 暴露，以及新的有希望的生物标记物和治疗方法的出现。我们的长期目标是 研究方案是提高人口和人的水平的有效性和效率 膀胱癌的预防、检测和治疗方法 约束条件。目前提案的总体目标是解决监测中的主要问题， 用比较数学模型研究膀胱癌的治疗、预防和诊断。 我们将实现六个具体目标：(1)完成开发、校准和验证 膀胱癌的两个独立人口模型；(2)解释膀胱癌的长期趋势 与关键人群亚组烟草使用趋势有关的发病率，并估计 1964年卫生局局长的吸烟建议；(3)评估戒烟的有效性， 为预防膀胱癌发病率和死亡率而采取的减少和预防干预措施； 评估通用和定制/以患者为中心的监测策略的有效性和成本效益 对于非肌肉浸润性膀胱癌患者；(5)评估 器官受限膀胱癌的治疗；及(6)评估膀胱癌筛查的效果 高危人群中的癌症。

Abstract Bladder cancer is the second most common genitourinary malignancy in the US with approximately 80,000 new cases and 17,700 deaths each year. It is a heterogeneous set of diseases that range from locally treatable superficial tumors that are generally not life-threatening but require chronic management, to advanced disease that requires multimodal invasive treatments and has higher risk of distal metastasis and death. It is the ninth most expensive cancer overall in the US, and, per diagnosed patient, the most expensive cancer to manage. Risk factors for bladder cancer broadly include chemical and environmental exposures such as cigarette smoking and chemical carcinogens that are ingested or found in the workplace, as well as genetic abnormalities and chronic bladder irritation. Outcomes for bladder cancer have remained relatively stable in the last two decades. However, opportunities abound to improve the prevention, detection, and management of bladder cancer. The advent of novel biomarkers, and novel treatments, including immunotherapies (checkpoint inhibitors), gene therapies, and antibody-drug conjugates may have a large impact in coming years. Bladder cancer is amenable to population modeling because it has high morbidity, mortality, and cost, is likely preventable by minimizing smoking and toxin exposure, and the emergence of novel promising biomarkers and treatments. The long-term goal of our research program is to improve the effectiveness and efficiency of population- and person-level approaches to bladder cancer prevention, detection, and management given current knowledge and constraints. The overall objective of the current proposal is to address major questions in the surveillance, treatment, prevention, and diagnosis of bladder cancer by means of comparative mathematical modeling. We will address six specific aims: We will (1) complete the development, calibration, and validation of two independent population models of bladder cancer; (2) explain secular trends in bladder cancer incidence in relation to trends in tobacco use in key population subgroups and estimate the impact of the 1964 Surgeon General’s smoking recommendations; (3) assess the effectiveness of smoking cessation, reduction and prevention interventions for the prevention of bladder cancer incidence and mortality; (4) assess the effectiveness and cost-effectiveness of generic and tailored/patient-centric surveillance policies for patients with non-muscle invasive bladder cancer; (5) assess the comparative effectiveness of treatments for organ-confined bladder cancer; and (6) assess the effectiveness of screening for bladder cancer among high-risk subgroups.