Development and validation of a survival nomogram for muscle-invasive bladder cancer in the elderly: using competing risk models and propensity matching to apply the prediction tool

Chenghao Zhanghuang, Zhaoxia Zhang, Hongchao Jiang, Jinkui Wang, Zhigang Yao, Fengming Ji, Chengchuan Wu, Zhen Yang, Yucheng Xie, Haoyu Tang, Bing Yan
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Abstract

Aim: Patients with muscle-invasive bladder cancer (MIBC) have a low survival rate, with a 5-year survival of approximately 45%, regardless of the treatment received. The risk of death within 5 years after radical cystectomy in patients with MIBC remains as high as 60%. Over 80% of patients with bladder cancer are over 65. Therefore, identifying prognostic correlates associated with radical cystectomy in older patients with MIBC could improve survival rates. In addition, radiotherapy and chemotherapy are particularly important as adjuvant treatments for MIBC patients undergoing radical cystectomy. Therefore, this study aimed to find risk factors for cancer-specific survival (CSS) and overall survival (OS) after radical cystectomy in elderly MIBC patients. The difference in survival between radiotherapy and chemotherapy was analyzed by Kaplan-Meier (K-M) curves to provide theoretical support for whether radiotherapy is recommended for such patients. Methods: Patients 65 or older diagnosed with MIBC with radical cystectomy between 2004-2018 were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. 2004-2015 patients were subjected to column line plot production and internal validation, and 2016-2018 patients were subjected to external temporal validation. A single-factor COX regression model was first used to screen for prognostic correlates. Then a multi-factor COX regression model was used to screen for independent risk factors. A nomogram was constructed by using independent risk factors. The accuracy and reliability of the nomogram were examined using calibration curves, consistency index (C-index), and area under subjects (AUC) as operational characteristic curves. Decision curve analysis (DCA) was performed to evaluate the clinical value of the prediction model. Results: A total of 11,557 patients were included in this study, divided into training set (N = 4,712), validation set (N = 4,810) and external validation set (N = 2,035). Multivariate COX regression models showed that chemotherapy, radiotherapy, TNM stage, race, and age were independent risk factors for CSS and OS patients. We constructed a nomogram to predict CSS and OS in elderly MIBC patients undergoing radical cystectomy. The C-indexes were 0.692 (95%CI: 0.680-0.704) and 0.690 (95%CI: 0.678-0.702) for the CSS training and validation sets, respectively, and 0.674 for the OS training and validation sets (95%CI: 0.664-0.684) and 0.672 (95%CI: 0.662-0.682) for the OS training and validation sets, respectively. The C-index of the external validation set CSS was 0.731 (95%CI: 709-0.753), and that of OS was 0.721 (95%CI: 0.701-0.741), indicating that the nomogram prediction model has good discriminative power. The calibration curves and AUC also suggested that the nomogram had good accuracy and discrimination. In addition, the KM curves of propensity-matched pre- and post-radiotherapy showed that radiotherapy was detrimental to patient survival. Meanwhile, chemotherapy favored OS and short-term CSS but not long-term CSS. Conclusions: We established a nomogram to predict the CSS and OS in elderly MIBC patients undergoing radical cystectomy. After internal cross-validation and external validation, the nomogram prediction model showed good accuracy and reliability, and the DCA results showed that the nomogram has good clinical value. In addition, this study gave good suggestions on whether radiotherapy or chemotherapy is necessary for radical cystectomy in elderly MIBC patients.
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老年人肌肉浸润性膀胱癌生存图的开发和验证:使用竞争风险模型和倾向匹配来应用预测工具
目的:肌肉浸润性膀胱癌(MIBC)患者的生存率很低,无论接受何种治疗,其5年生存率约为45%。MIBC患者根治性膀胱切除术后5年内的死亡风险仍高达60%。超过80%的膀胱癌患者年龄在65岁以上。因此,确定老年MIBC患者根治性膀胱切除术的预后相关性可以提高生存率。此外,放疗和化疗作为辅助治疗对于行根治性膀胱切除术的MIBC患者尤为重要。因此,本研究旨在发现老年MIBC患者根治性膀胱切除术后癌症特异性生存(CSS)和总生存(OS)的危险因素。通过Kaplan-Meier (K-M)曲线分析放疗与化疗的生存差异,为该类患者是否推荐放疗提供理论支持。方法:从2004-2018年监测、流行病学和最终结果(SEER)数据库中获得65岁或以上诊断为MIBC并行根治性膀胱切除术的患者。2004-2015年患者进行柱线图制作和内部验证,2016-2018年患者进行外部时间验证。单因素COX回归模型首次用于筛选预后相关因素。然后采用多因素COX回归模型筛选独立危险因素。采用独立的危险因素构建了nomogram。采用标定曲线、一致性指数(C-index)和被试面积(AUC)作为操作特征曲线,对图的准确性和可靠性进行了检验。采用决策曲线分析(DCA)评价预测模型的临床应用价值。结果:共纳入11,557例患者,分为训练集(N = 4,712)、验证集(N = 4,810)和外部验证集(N = 2,035)。多因素COX回归模型显示,化疗、放疗、TNM分期、种族和年龄是CSS和OS患者的独立危险因素。我们构建了一个nomogram来预测行根治性膀胱切除术的老年MIBC患者的CSS和OS。CSS训练集和验证集的c指数分别为0.692 (95%CI: 0.680-0.704)和0.690 (95%CI: 0.678-0.702), OS训练集和验证集的c指数分别为0.674 (95%CI: 0.664-0.684)和0.672 (95%CI: 0.662-0.682)。外部验证集CSS的c指数为0.731 (95%CI: 709 ~ 0.753), OS的c指数为0.721 (95%CI: 0.701 ~ 0.741),说明nomogram预测模型具有较好的判别能力。标定曲线和AUC也表明该图具有较好的准确度和鉴别性。此外,放疗前后倾向匹配的KM曲线显示放疗对患者生存不利。化疗对OS和短期CSS有利,但对长期CSS不利。结论:我们建立了预测行根治性膀胱切除术的老年MIBC患者的CSS和OS的nomogram。经内部交叉验证和外部验证,nomogram预测模型具有较好的准确性和可靠性,DCA结果显示nomogram具有较好的临床应用价值。此外,本研究对老年MIBC患者根治性膀胱切除术是否需要放疗或化疗提出了很好的建议。
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CiteScore
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5.30%
发文量
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