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[一种预测根治性肾切除术后总生存期的新型列线图的建立与验证]

[Establishment and validation of a novel nomogram to predict overall survival after radical nephrectomy].

作者信息

Xiong L B, Zou X P, Ning K, Luo X, Peng Y L, Zhou Z H, Wang J, Li Z, Yu C P, Dong P, Guo S J, Han H, Zhou F J, Zhang Z L

机构信息

Department of Urology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.

出版信息

Zhonghua Zhong Liu Za Zhi. 2023 Aug 23;45(8):681-689. doi: 10.3760/cma.j.cn112152-20221027-00722.

Abstract

To establish a nomogram prognostic model for predicting the 5-, 10-, and 15-year overall survival (OS) of non-metastatic renal cell carcinoma patients managed with radical nephrectomy (RN), compare the modelled results with the results of pure pathologic staging, the Karakiewicz nomogram and the Mayo Clinic Stage, Size, Grade, and Necrosis (SSIGN) score commonly used in foreign countries, and stratify the patients into different prognostic risk subgroups. A total of 1 246 non-metastatic renal cell carcinoma patients managed with RN in Sun Yat-sen University Cancer Center (SYSUCC) from 1999 to 2020 were retrospectively analyzed. Multivariate Cox regression analysis was used to screen the variables that influence the prognosis for nomogram establishment, and the bootstrap random sampling was used for internal validation. The time-receiver operating characteristic curve (ROC), the calibration curve and the clinical decision curve analysis (DCA) were applied to evaluate the nomogram. The prediction efficacy of the nomogram and that of the pure pathologic staging, the Karakiewicz nomogram and the SSIGN score was compared through the area under the curve (AUC). Finally, patients were stratified into different risk subgroups according to our nomogram scores. A total of 1 246 patients managed with RN were enrolled in this study. Multivariate Cox regression analysis showed that age, smoking history, pathological nuclear grade, sarcomatoid differentiation, tumor necrosis and pathological T and N stages were independent prognostic factors for RN patients (all <0.05). A nomogram model named SYSUCC based on these factors was built to predict the 5-, 10-, and 15-year survival rate of the participating patients. In the bootstrap random sampling with 1 000 iterations, all these factors occurred for more than 800 times as independent predictors. The Harrell's concordance index (C-index) of SYSUCC was higher compared with pure pathological staging [0.770 (95% 0.716-0.823) vs 0.674 (95% 0.621-0.728)]. The calibration curve showed that the survival rate as predicted by the SYSUCC model simulated the actual rate, while the clinical DCA showed that the SYSUCC nomogram has a benefit in certain probability ranges. In the ROC analysis that included 857 patients with detailed pathological nuclear stages, the nomogram had a larger AUC (5-/10-year AUC: 0.823/0.804) and better discriminating ability than pure pathological staging (5-/10-year AUC: 0.701/0.658), Karakiewicz nomogram (5-/10-year AUC: 0.772/0.734) and SSIGN score (5-/10-year AUC: 0.792/0.750) in predicting the 5-/10-year OS of RN patients (all <0.05). In addition, the AUC of the SYSUCC nomogram for predicting the 15-year OS (0.820) was larger than that of the SSIGN score (0.709), and there was no statistical difference (<0.05) between the SYSUCC nomogram, pure pathological staging (0.773) and the Karakiewicz nomogram (0.826). The calibration curve was close to the standard curve, which indicated that the model has good predictive performance. Finally, patients were stratified into low-, intermediate-, and high-risk subgroups (738, 379 and 129, respectively) according to the SYSUCC nomogram scores, among whom patients in intermediate- and high-risk subgroups had a worse OS than patients in the low-risk subgroup (intermediate-risk group vs. low-risk group: =4.33, 95% 3.22-5.81, <0.001; high-risk group vs low-risk group: =11.95, 95% 8.29-17.24, <0.001), and the high-risk subgroup had a worse OS than the intermediate-risk group (=2.63, 95% : 1.88-3.68, <0.001). Age, smoking history, pathological nuclear grade, sarcomatoid differentiation, tumor necrosis and pathological stage were independent prognostic factors for non-metastasis renal cell carcinoma patients after RN. The SYSUCC nomogram based on these independent prognostic factors can better predict the 5-, 10-, and 15-year OS than pure pathological staging, the Karakiewicz nomogram and the SSIGN score of patients after RN. In addition, the SYSUCC nomogram has good discrimination, agreement, risk stratification and clinical application potential.

摘要

建立列线图预后模型以预测接受根治性肾切除术(RN)的非转移性肾细胞癌患者的5年、10年和15年总生存期(OS),将建模结果与国外常用的单纯病理分期、Karakiewicz列线图以及梅奥诊所分期、大小、分级和坏死(SSIGN)评分的结果进行比较,并将患者分层为不同的预后风险亚组。回顾性分析了1999年至2020年在中山大学肿瘤防治中心(SYSUCC)接受RN治疗的1246例非转移性肾细胞癌患者。采用多因素Cox回归分析筛选影响列线图建立的预后变量,并采用自抽样随机抽样进行内部验证。应用时间-受试者工作特征曲线(ROC)、校准曲线和临床决策曲线分析(DCA)对列线图进行评估。通过曲线下面积(AUC)比较列线图与单纯病理分期、Karakiewicz列线图和SSIGN评分的预测效能。最后,根据我们的列线图评分将患者分层为不同的风险亚组。本研究共纳入1246例接受RN治疗的患者。多因素Cox回归分析显示,年龄、吸烟史、病理核分级、肉瘤样分化、肿瘤坏死以及病理T和N分期是RN患者的独立预后因素(均<0.05)。基于这些因素构建了一个名为SYSUCC的列线图模型,以预测参与患者的5年、10年和15年生存率。在1000次迭代的自抽样随机抽样中,所有这些因素作为独立预测因子出现超过800次。SYSUCC的Harrell一致性指数(C指数)高于单纯病理分期[0.770(95% 0.716 - 0.823)对0.674(95% 0.621 - 0.728)]。校准曲线显示,SYSUCC模型预测的生存率模拟了实际生存率,而临床DCA显示SYSUCC列线图在特定概率范围内具有优势。在纳入857例有详细病理核分期患者的ROC分析中,列线图在预测RN患者的5年/10年OS方面比单纯病理分期(5年/10年AUC:0.701/0.658)、Karakiewicz列线图(5年/10年AUC:0.772/0.734)和SSIGN评分(5年/10年AUC:0.792/0.750)具有更大的AUC(5年/10年AUC:0.823/0.804)和更好的区分能力(均<0.05)。此外,SYSUCC列线图预测15年OS的AUC(0.820)大于SSIGN评分(0.709),SYSUCC列线图、单纯病理分期(0.773)和Karakiewicz列线图(0.826)之间无统计学差异(<0.05)。校准曲线接近标准曲线,表明该模型具有良好的预测性能。最后,根据SYSUCC列线图评分将患者分层为低、中、高风险亚组(分别为738例、379例和129例),其中中、高风险亚组患者的OS比低风险亚组患者差(中风险组与低风险组:=4.33,95% 3.22 - 5.81,<0.001;高风险组与低风险组:=11.95,95% 8.29 - 17.24,<0.001),且高风险亚组患者的OS比中风险组差(=2.63,95%:1.88 - 3.68,<0.001)。年龄、吸烟史、病理核分级、肉瘤样分化、肿瘤坏死和病理分期是RN术后非转移性肾细胞癌患者的独立预后因素。基于这些独立预后因素的SYSUCC列线图在预测RN术后患者的5年、10年和15年OS方面比单纯病理分期、Karakiewicz列线图和SSIGN评分表现更好。此外,SYSUCC列线图具有良好的区分度、一致性、风险分层和临床应用潜力。

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