术前癌胚抗原/肿瘤大小对直肠癌的预后价值。

BACKGROUND: Carcinoembryonic antigen (CEA) is a commonly used biomarker in colorectal cancer. However, controversy exists regarding the insufficient prognostic value of preoperative serum CEA alone in rectal cancer. Here, we combined preoperative serum CEA and the maximum tumor diameter to correct the CEA level, which may better reflect the malignancy of rectal cancer. AIM: To assess the prognostic impact of preoperative CEA/tumor size in rectal cancer. METHODS: We retrospectively reviewed 696 stage I to III rectal cancer patients who underwent curative tumor resection from 2007 to 2012. These patients were randomly divided into two cohorts for cross-validation: training cohort and validation cohort. The training cohort was used to generate an optimal cutoff point and the validation cohort was used to further validate the model. Maximally selected rank statistics were used to identify the optimum cutoff for CEA/tumor size. The Kaplan-Meier method and log-rank test were used to plot the survival curve and to compare the survival data. Univariate and multivariate Cox regression analyses were used to determine the prognostic value of CEA/tumor size. The primary and secondary outcomes were overall survival (OS) and disease-free survival (DFS), respectively. RESULTS: In all, 556 patients who satisfied both the inclusion and exclusion criteria were included and randomly divided into the training cohort (2/3 of 556, = 371) and the validation cohort (1/3 of 556, = 185). The cutoff was 2.429 ng/mL per cm. Comparison of the baseline data showed that high CEA/tumor size was correlated with older age, high TNM stage, the presence of perineural invasion, high CEA, and high carbohydrate antigen 19-9 (CA 19-9). Kaplan-Meier curves showed a manifest reduction in 5-year OS (training cohort: 56.7% 81.1%, < 0.001; validation cohort: 58.8% 85.6%, < 0.001) and DFS (training cohort: 52.5% 71.9%, = 0.02; validation cohort: 50.3% 79.3%, = 0.002) in the high CEA/tumor size group compared with the low CEA/tumor size group. Univariate and multivariate analyses identified CEA/tumor size as an independent prognostic factor for OS (training cohort: hazard ratio (HR) = 2.18, 95% confidence interval (CI): 1.28-3.73, = 0.004; validation cohort: HR = 4.83, 95%CI: 2.21-10.52, < 0.001) as well as DFS (training cohort: HR = 1.47, 95%CI: 0.93-2.33, = 0.096; validation cohort: HR = 2.61, 95%CI: 1.38-4.95, = 0.003). CONCLUSION: Preoperative CEA/tumor size is an independent prognostic factor for patients with stage I-III rectal cancer. Higher CEA/tumor size is associated with worse OS and DFS.

背景：癌胚抗原（CEA）是结直肠癌中常用的生物标志物。然而，术前血清 CEA 单独在直肠癌中的预后价值不足仍存在争议。在这里，我们将术前血清 CEA 和最大肿瘤直径相结合来校正 CEA 水平，这可能更好地反映直肠癌的恶性程度。

目的：评估术前 CEA/肿瘤大小在直肠癌中的预后影响。

方法：我们回顾性分析了 2007 年至 2012 年期间接受根治性肿瘤切除术的 696 例 I 期至 III 期直肠癌症患者。这些患者被随机分为两个验证队列进行交叉验证：训练队列和验证队列。训练队列用于生成最佳截断点，验证队列用于进一步验证模型。最大选择秩统计用于确定 CEA/肿瘤大小的最佳截断点。Kaplan-Meier 法和对数秩检验用于绘制生存曲线和比较生存数据。单因素和多因素 Cox 回归分析用于确定 CEA/肿瘤大小的预后价值。主要和次要结局分别是总生存期（OS）和无病生存期（DFS）。

结果：总共纳入了符合纳入和排除标准的 556 例患者，并随机分为训练队列（556 例的 2/3， = 371）和验证队列（556 例的 1/3， = 185）。截断值为 2.429ng/mL/ cm。基线数据比较显示，高 CEA/肿瘤大小与年龄较大、较高的 TNM 分期、神经周围侵犯、高 CEA 和高糖抗原 19-9（CA 19-9）有关。Kaplan-Meier 曲线显示，在高 CEA/肿瘤大小组中，5 年 OS（训练队列：56.7% 81.1%， < 0.001；验证队列：58.8% 85.6%， < 0.001）和 DFS（训练队列：52.5% 71.9%， = 0.02；验证队列：50.3% 79.3%， = 0.002）明显降低。单因素和多因素分析确定 CEA/肿瘤大小是 OS（训练队列：风险比（HR）= 2.18，95%置信区间（CI）：1.28-3.73， = 0.004；验证队列：HR = 4.83，95%CI：2.21-10.52， < 0.001）和 DFS（训练队列：HR = 1.47，95%CI：0.93-2.33， = 0.096；验证队列：HR = 2.61，95%CI：1.38-4.95， = 0.003）的独立预后因素。

结论：术前 CEA/肿瘤大小是 I-III 期直肠癌患者的独立预后因素。较高的 CEA/肿瘤大小与较差的 OS 和 DFS 相关。