Zhou Siyu, Sheng Nengquan, Ren Jiazi, He Qian, Zhang Yaya, Gong Jianfeng, Wang Zhigang
Department of Gastrointestinal Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
College of Clinical Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Front Oncol. 2021 Oct 7;11:741309. doi: 10.3389/fonc.2021.741309. eCollection 2021.
Recently, a few researches focus on the correlation between postoperative carcinoembryonic antigen (post-CEA) and the outcome of colorectal cancer (CRC), but none investigates the predictive value of post-CEA in a prognostic model. Besides, current recommendations on the frequency of post-CEA surveillance are not individualized and well followed. There is an absence of identification of patients who are more likely to have abnormal post-CEA levels and need more frequent CEA measurements.
Consecutive CRC patients who underwent curative surgery were enrolled and randomly divided into the discovery (n=352) and testing cohort (n=233). Impacts of preoperative CEA (pre-CEA) and post-CEA on prognosis were assessed. Cox regression model was applied to develop prognostic nomograms, which were validated by the concordance index (C-index), calibration curve, and receiver operating characteristic curve (ROC) analysis. And prediction improvement of the nomograms was assessed with net reclassification improvement (NRI) and integrated discrimination improvement (IDI). Logistic regression was used to identify predictive risk factors and construct the prediction model for post-CEA elevation.
Post-CEA independently predicted overall survival (OS) and disease-free survival (DFS), while pre-CEA did not. Post-CEA elevation represented higher risks in patients with normal pre-CEA, compared to those with persistent elevated CEA. The nomograms for OS and DFS were established with body mass index, tumor differentiation, N stage, lymphocyte-to-monocyte ratio, and post-CEA. The nomograms showed good calibration and superior discrimination than pTNM stage, with the C-index of 0.783 and 0.759 in the discovery set and 0.712 and 0.774 in the testing set for OS and DFS, respectively. Comparisons between models using IDI and NRI implied that the nomograms performed better than pTNM stage and the predictive power could be improved with the addition of post-CEA. The prediction model for post-CEA elevation was established with age, platelet-to-lymphocyte ratio, preoperative CA19-9, and pre-CEA. The AUC of the model in the two cohorts was 0.802 and 0.764, respectively.
Elevated post-CEA was a strong indicator of poor prognosis. The addition of post-CEA significantly enhanced the performance of prognostic nomograms. And the prediction model for post-CEA elevation may help identify patients who ought to reasonably receive more intensive postoperative surveillance of CEA levels.
最近,一些研究聚焦于术后癌胚抗原(post-CEA)与结直肠癌(CRC)预后之间的相关性,但尚无研究调查post-CEA在预后模型中的预测价值。此外,目前关于post-CEA监测频率的建议未实现个体化且未得到充分遵循。缺乏对更可能出现post-CEA水平异常且需要更频繁进行CEA检测的患者的识别。
纳入接受根治性手术的连续性CRC患者,并随机分为发现队列(n = 352)和验证队列(n = 233)。评估术前CEA(pre-CEA)和post-CEA对预后的影响。应用Cox回归模型构建预后列线图,并通过一致性指数(C-index)、校准曲线和受试者工作特征曲线(ROC)分析进行验证。使用净重新分类改善(NRI)和综合判别改善(IDI)评估列线图的预测改善情况。采用逻辑回归识别预测风险因素并构建post-CEA升高的预测模型。
Post-CEA可独立预测总生存期(OS)和无病生存期(DFS),而pre-CEA则不能。与术前CEA持续升高的患者相比,术前CEA正常的患者中post-CEA升高代表更高风险。根据体重指数、肿瘤分化程度、N分期、淋巴细胞与单核细胞比值和post-CEA建立了OS和DFS的列线图。列线图显示出良好的校准,且辨别能力优于pTNM分期,在发现队列中OS和DFS的C-index分别为0.783和0.759,在验证队列中分别为0.712和0.774。使用IDI和NRI对模型进行比较表明,列线图的表现优于pTNM分期,且加入post-CEA后预测能力可得到提高。根据年龄、血小板与淋巴细胞比值、术前CA19-9和pre-CEA建立了post-CEA升高的预测模型。该模型在两个队列中的AUC分别为0.802和0.764。
Post-CEA升高是预后不良的有力指标。加入post-CEA可显著提高预后列线图的性能。而post-CEA升高的预测模型可能有助于识别那些应该合理接受更密集的术后CEA水平监测的患者。