Zhang Qian, Xu Rongxuan, Zhen Wenchong, Bai Xueting, Li Zihan, Zhang Yixin, Wu Wei, Yao Zhihan, Li Xiaofeng
Department of Public Health, Dalian Medical University, Dalian, Liaoning, China.
Sci Rep. 2025 Jul 7;15(1):24269. doi: 10.1038/s41598-025-05824-1.
Elderly patients with colorectal cancer (CRC) face an elevated risk of cardiovascular and cerebrovascular death (CVD), yet few studies have explicitly addressed CVD as a competing risk event. Traditional survival analyses often overlook competing risks, potentially biasing prognostic estimates. This study aimed to evaluate cancer-specific survival (CSS) in elderly patients with stage I-III CRC after surgery using Fine-Gray subdistribution hazard model and a random survival forest (RSF) approach, thereby improving clinical decision-making. Older patients (≥ 65 years) with stage I-III CRC between 2010 and 2015 were selected from the Surveillance, Epidemiology and End Results (SEER) database. In addition, data from 2018-2021 in the database is extracted as an external validation set. In this study, CVD was considered as a competing risk event of CRC specific death, and Fine-gray regression analysis was used to construct the Fine-Gray subdistribution hazard model and a competing risk-based random survival forest (RSF) model were used to analyze postoperative cancer-specific survival (CSS) in elderly patients with stage I-III CRC as the best mechanism to obtain more precise results and help make clinical management decisions. Predictors included age, sex, race, marital status, grade, T stage, N stage, histological type, primary site, carcinoembryonic antigen (CEA), perineural invasion, tumor deposits, tumor size. Model performance was assessed through discrimination[C-index, area under the receiver operating curve (AUC)], accuracy[Brier score (BS)], and clinical utility[decision curve analysis (DCA)]. In addition, we also visualized the Fine-Gray subdistribution hazard model with a nomogram and compared it with the nomogram of the Cox model. A total of 19195 elderly (≥ 65 years) patients with stage I-III CRC who underwent primary site surgery between 2010 and 2015 were included in the study. There were 10305 deaths among all patients, including 4253 deaths specific to CRC, 2571 deaths due to cardiovascular and cerebrovascular diseases, 379 deaths due to other neoplastic diseases and 3120 deaths due to other non neoplastic diseases. The Fine-Gray subdistribution risk and RSF models we developed have good discrimination power and accuracy. The Fine-Gray subdistribution risk model:the 1-year, 3-year and 5-year C-index was 0.771, 0.775 and 0.759 in the train set, and 0.744, 0.762 and 0.753 in the internal test set . The 1-year, and 3-year C-index in the external validation set was 0.762 and 0.775.The RSF model:the 1-year, 3-year and 5-year AUC was 0.782 (95% CI 0.765, 0.798), 0.8 (95% CI 0.79, 0.811) and 0.786 (95% CI 0.776, 0.796) in the train set, and 0.754 (95% CI 0.727, 0.782), 0.786 (95% CI 0.769, 0.802) and 0.782 (95% CI 0.766, 0.797) in the internal test set. The 1-year and 3-year AUC was 0.77 (95% CI 0.749, 0.79) and 0.83 (95% CI 0.786, 0.82) in the external verification set. The 1-year, 3-year and 5-year BS was 0.053 (95% CI 0.050, 0.056), 0.104 (95% CI 0.101, 0.107) and 0.128 (95% CI 0.124, 0.132) in the train set, and 0.050 (95% CI0.044, 0.056), 0.106 (95% CI 0.098, 0.112) and 0.130 (95% CI 0.124, 0.136) in the internal test set. The 1-year and 3-year BS was 0.042 (5% CI 0.038, 0.044) and 0.085 (95% CI 0.078, 0.092) in the external verification set. The RSF model we established has good discrimination power and accuracy.The 1-year, 3-year, 5-year C-index was 0.801, 0.788 and 0.769 in the train set, and 0.744, 0.754 and 0.745 in the internal test set of the RSF model. The 1-year, and 3-year C-index in the external validation set was 0.761 and 0.771.The 1-year, 3-year and 5-year AUC was 0.792 (95% CI 0.776, 0.807), 0.813 (95% CI 0.802, 0.823) and 0.801 (95% CI 0.791, 0.811) in the train set and 0.749 (95% CI 0.721, 0.777), 0.779 (95% CI 0.762, 0.796) and 0.782 (95% CI 0.767, 0.798) in the internal test set (Fig. 6a, b). The 1-year and 3-year AUC was 0.767 (95% CI 0.747, 0.788) and 0.8 (95% CI 0.783, 0.817) in the external verification set (Fig. 7c). The 1-year, 3-year and 5-year BS was 0.053 (95% CI 0.51, 0.057), 0.105 (95% CI 0.102, 0.108) and 0.131 (95% CI 0.128, 0.134) in the train set, and 0.051 (95% CI0.45, 0.055), 0.109 (95% CI 0.102, 0.116) and 0.132 (95% CI 0.125, 0.140) in the internal test set (Fig. 7d, e). The 1-year and 3-year BS was 0.042 (95% CI 0.038, 0.045) and 0.086 (95% CI 0.082, 0.091) in the external verification set (Fig. 7f).DCA showed that models could lead to higher clinical benefits for patients. Through the nomogram we constructed, it can be calculated that the traditional Cox model overestimated the CSS of patients compared with the Fine-Gray subdistribution risk model. Based on the SEER database, the Fine-Gray subdistribution hazard model and the competing risk-based RSF model were used to predict CSS after CRC surgery in elderly patients, and models performed well. Incorporating competing risk events in survival analysis improves result accuracy and supports personalized clinical decision-making for elderly CRC patients.
老年结直肠癌(CRC)患者面临心血管和脑血管死亡(CVD)风险升高的问题,但很少有研究明确将CVD视为竞争风险事件。传统生存分析常常忽略竞争风险,这可能会使预后估计产生偏差。本研究旨在使用Fine-Gray亚分布风险模型和随机生存森林(RSF)方法评估I-III期CRC老年患者术后的癌症特异性生存(CSS),从而改善临床决策。从监测、流行病学和最终结果(SEER)数据库中选取2010年至2015年间年龄≥65岁的I-III期CRC老年患者。此外,提取数据库中2018 - 2021年的数据作为外部验证集。在本研究中,将CVD视为CRC特异性死亡的竞争风险事件,使用Fine-gray回归分析构建Fine-Gray亚分布风险模型,并使用基于竞争风险的随机生存森林(RSF)模型分析I-III期CRC老年患者术后的癌症特异性生存(CSS),作为获得更精确结果并帮助做出临床管理决策的最佳方法。预测因素包括年龄、性别、种族、婚姻状况、分级、T分期、N分期、组织学类型、原发部位、癌胚抗原(CEA)、神经周围侵犯、肿瘤沉积物、肿瘤大小。通过区分度[C指数、受试者操作特征曲线下面积(AUC)]、准确性[Brier评分(BS)]和临床实用性[决策曲线分析(DCA)]评估模型性能。此外,我们还用列线图直观展示了Fine-Gray亚分布风险模型,并将其与Cox模型的列线图进行比较。本研究共纳入2010年至2015年间19195例接受原发部位手术的年龄≥65岁的I-III期CRC老年患者。所有患者中有10305例死亡,其中包括4253例CRC特异性死亡、2571例心血管和脑血管疾病死亡、379例其他肿瘤疾病死亡以及3120例其他非肿瘤疾病死亡。我们开发的Fine-Gray亚分布风险模型和RSF模型具有良好的区分能力和准确性。Fine-Gray亚分布风险模型:训练集中1年、3年和5年的C指数分别为0.771、0.775和0.759,内部测试集中分别为0.744、0.762和0.753。外部验证集中1年和3年的C指数分别为0.762和0.775。RSF模型:训练集中1年、3年和5年的AUC分别为0.782(95%CI 0.765,0.798)、0.8(95%CI 0.79,0.811)和0.786(95%CI 0.776,0.796),内部测试集中分别为0.754(95%CI 0.727,0.782)、0.786(95%CI 0.769,0.802)和0.782(95%CI 0.766,0.797)。外部验证集中1年和3年的AUC分别为0.77(95%CI 0.749,0.79)和0.83(95%CI 0.786,0.82)。训练集中1年、3年和5年的BS分别为0.053(95%CI 0.050,0.056)、0.104(95%CI 0.101,0.107)和0.128(95%CI 0.124,0.132),内部测试集中分别为0.050(95%CI0.044,0.056)、0.106(95%CI 0.098,0.112)和0.130(95%CI 0.124,0.136)。外部验证集中1年和3年的BS分别为0.042(5%CI 0.038,0.044)和0.085(95%CI 0.078,0.092)。我们建立的RSF模型具有良好的区分能力和准确性。RSF模型训练集中1年、3年、5年的C指数分别为0.801、0.788和0.769,内部测试集中分别为0.744、0.754和0.745。外部验证集中1年和3年的C指数分别为0.761和0.771。训练集中1年、3年和5年的AUC分别为0.792(95%CI 0.776,0.807)、0.813(95%CI 0.802,0.823)和0.801(95%CI 0.791,0.811),内部测试集中分别为0.749(95%CI 0.721,0.777)、0.779(95%CI 0.762,0.796)和0.782(95%CI 0.767,0.798)(图6a,b)。外部验证集中1年和3年的AUC分别为0.767(95%CI 0.747,0.788)和0.8(95%CI 0.783,0.817)(图7c)。训练集中1年、3年和5年的BS分别为0.053(95%CI 0.51,0.057)、0.105(95%CI 0.102,0.108)和0.131(95%CI 0.128,0.134),内部测试集中分别为0.051(95%CI0.45,0.055)、0.109(95%CI 0.102,0.116)和0.132(95%CI 0.125,0.140)(图7d,e)。外部验证集中1年和3年的BS分别为0.042(95%CI 0.038,0.045)和0.086(95%CI 0.082,0.091)(图7f)。决策曲线分析表明模型可为患者带来更高的临床获益。通过我们构建的列线图可以计算出,与Fine-Gray亚分布风险模型相比,传统Cox模型高估了患者的CSS。基于SEER数据库,使用Fine-Gray亚分布风险模型和基于竞争风险的RSF模型预测老年CRC患者CRC术后的CSS,模型表现良好。在生存分析中纳入竞争风险事件可提高结果准确性,并支持为老年CRC患者进行个性化临床决策。
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