Population Modeling of Bladder Cancer Detection and Control

摘要 膀胱癌是美国第二常见的泌尿生殖系统恶性肿瘤， 每年新增8万例，死亡1.77万例。它是一组异质性疾病，范围从 局部可治疗的浅表肿瘤，通常不危及生命，但需要长期管理， 需要多模式侵入性治疗且远端转移风险较高的晚期疾病 与死它是美国第九大最昂贵的癌症，也是每个确诊患者最昂贵的癌症。 昂贵的癌症治疗膀胱癌的危险因素广泛包括化学和环境 暴露，如吸烟和化学致癌物，摄入或发现在 工作场所，以及遗传异常和慢性膀胱刺激。膀胱癌的预后 在过去的二十年里保持相对稳定。然而，有很多机会可以改善 膀胱癌的预防、检测和管理。新生物标志物的出现，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 共轭物在未来几年可能会产生很大的影响。膀胱癌适合人群建模 因为它具有高发病率、高死亡率和高成本，通过减少吸烟和毒素， 暴露，以及新的有前途的生物标志物和治疗方法的出现。我们的长期目标是 研究计划是为了提高人口和人的水平的有效性和效率 膀胱癌的预防，检测和管理的方法， 约束本提案的总体目标是解决监督中的主要问题， 膀胱癌的治疗、预防和诊断。 我们将实现六个具体目标：我们将（1）完成以下的开发、校准和验证 膀胱癌的两个独立人群模型;（2）解释膀胱癌的长期趋势 吸烟率与主要人口亚组吸烟趋势的关系，并估计 1964年卫生部长的吸烟建议;（3）评估戒烟的有效性， 减少和预防膀胱癌的发病率和死亡率的干预措施;（4） 评估通用和定制/以患者为中心的监测政策的有效性和成本效益 对于非肌层浸润性膀胱癌患者;（5）评估 器官局限性膀胱癌的治疗;以及（6）评估膀胱癌筛查的有效性。 高风险亚组中的癌症。

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.