Predicting Functional Decline and Clinical Outcomes in Newly Diagnosed Older Patients with Localized Bladder Cancer

项目总结/摘要： 老年癌症患者不成比例地被认为不适合积极治疗， 明确的癌症治疗率显著降低，结果不佳。我们缺乏有效的工具来可靠地预测 治疗相关不良事件的个性化风险和老年患者的显著结局，如功能 下降虽然指南提倡广泛采用老年评估（GA）来量化 老年癌症患者在治疗决策前的多维脆弱性，临床采用 与缺乏评价GA在临床实践中区分风险的能力的数据相关性较低 功能下降、不良临床和肿瘤学结局。此外，传统遗传算法不包括 经验证的肌肉质量指标可独立预测临床和肿瘤学结局。膀胱癌是 评估和开发个性化老年肿瘤风险分层工具的理想健康状况， 考虑到诊断时的中位年龄为73岁，合并症的基线患病率较高， 治疗相关的不良事件，以及如果不治疗的普遍致死性。我们的目标是量化功能 新诊断的膀胱癌患者的下降，并开发预测模型，将GA- 基于虚弱和肌肉指标的功能下降、治疗相关发病率和 mortality.具体目的是：（1A）描述老年人功能下降的患病率和预测因素 新诊断膀胱癌的成人，（1B）以确定基线虚弱和肌肉指标是否预测 功能下降，以及（2）评估虚弱、肌肉指标和治疗相关结局的相关性 (i.e.,不良事件、生存率）。为实现目标1，基线 将功能状态与前瞻性新诊断老年膀胱的3个月评估进行比较 癌症队列（N=250）接受治疗前基于GA的虚弱自我评估和肌肉指标， 将建立预测模型。对于目标2，我们将构建治疗相关的多变量模型， 不良事件、术后并发症和死亡率，包括基于GA的虚弱和肌肉指标 从一个强大的膀胱癌登记。这项创新的研究通过将经过验证的 GA工具增强了强大的身体组成数据。这项工作意义重大：它将是第一项研究， 描述老年膀胱癌患者功能下降的风险因素，同时解决急性需求 验证严格的个性化风险分层工具，将老年疾病纳入其中， 决策，确保与患者优先事项保持一致。这项工作将直接转化为成果的改善 并外推到其他恶性肿瘤。这个GEMSSTAR项目，指导 专业发展计划将帮助PI成为少数独立的PI之一。 研究人员具有交叉老化，泌尿肿瘤学和以患者为中心的结果研究的专业知识。

PROJECT SUMMARY/ABSTRACT: Older patients with cancer are disproportionately perceived as unfit for aggressive therapies, resulting in significantly lower rates of definitive cancer care and poor outcomes. We lack validated tools to reliably predict personalized risks of adverse treatment-related events and salient outcomes for older patients such as functional decline. While guidelines advocate for widespread adoption of Geriatric Assessments (GAs) to quantify multidimensional vulnerabilities prior to treatment decision-making in older patients with cancer, clinical adoption is low related to a dearth of data evaluating the ability of GAs in clinical practice to discriminate those at risk for functional decline, adverse clinical and oncologic outcomes. Furthermore, traditional GAs do not include validated metrics of muscle mass that independently predict clinical and oncologic outcomes. Bladder cancer is an ideal health condition in which to evaluate and develop personalized geriatric oncology risk stratification tools, given median age at diagnosis of 73 years, a high baseline prevalence of comorbidities, substantial risk of treatment-associated adverse events, and universal lethality if untreated. Our objective is to quantify functional decline in patients with newly diagnosed bladder cancer, and to develop prediction models incorporating GA- based frailty and muscle metrics for the outcomes of functional decline, treatment-associated morbidity and mortality. The Specific Aims are: (1A) To characterize prevalence and predictors of functional decline in older adults with newly diagnosed bladder cancer, (1B) to determine if baseline frailty and muscle metrics predict functional decline, and (2) To evaluate associations frailty, muscle metrics, and treatment-associated outcomes (i.e., adverse events, survival) in older adults with localized high-risk bladder cancer. To achieve Aim 1, baseline functional status will be compared with a 3-month assessment in a prospective newly diagnosed older bladder cancer cohort (N=250) undergoing a pretreatment GA-based frailty self-assessment and muscle metrics and a predictive model will be developed. For Aim 2, we will construct multivariable models for treatment-associated adverse events, postoperative complications, and mortality incorporating GA-based frailty and muscle metrics from a robust bladder cancer registry. This innovative study advances risk stratification by incorporating validated GA tools augmented with robust body composition data. This work is significant: it will be the first study to characterize risk factors for functional decline in older bladder cancer patients, while addressing the acute need to validate rigorous personalized risk stratification tools incorporating geriatric conditions to inform treatment decisions, ensuring alignment with patient priorities. This work will directly translate to improvements in outcomes of older patients with cancer and extrapolate to other malignancies. This GEMSSTAR project, mentoring committee, and professional development plan will help the PI to become one of the few independent investigators with expertise intersecting aging, urologic oncology, and patient-centered outcomes research.