Department of General Surgery, Xiangya Hospital, Central South University, Changsha, People's Republic of China.
Key Laboratory of Molecular Radiation Oncology Hunan Province, Changsha, People's Republic of China.
Cancer Med. 2023 Feb;12(3):2538-2550. doi: 10.1002/cam4.5099. Epub 2022 Aug 1.
Despite controversy over its origin and definition, the significance of tumour deposit (TD) has been underestimated in the tumour node metastasis (TNM) staging system for colon cancer, especially in stage III patients. We aimed to further confirm the prognostic value of TD in stage III colon cancer and to establish a more accurate 'coN' staging system combining TD and lymph node metastasis (LNM).
Information on stage III colon cancer patients with a definite TD status was retrospectively collected from the Surveillance, Epidemiology and End Results (SEER) database between 2010 and 2017. The effect of TD on prognosis was estimated using Cox regression analysis. Maximally selected rank statistics were used to select the optimal cut-off value of TD counts. The predictive power of conventional N staging and the new coN staging was evaluated and compared by Akaike's information criterion (AIC), Harrell's concordance index (C-index) and time-dependent receiver operating characteristic (ROC) curves. Clinicopathological data of stage III colon cancer patients in the Xiangya database from 2014 to 2018 were collected to validate the coN staging system.
A total of 39,185 patients with stage III colon cancer were included in our study: 38,446 in the SEER cohort and 739 in the Xiangya cohort. The incidence of TD in stage III colon cancer was approximately 30% (26% in SEER and 30% in the Xiangya database). TD was significantly associated with poorer overall survival (OS) (HR = 1.37, 95% CI 1.31-1.44, p < 0.001 in SEER). The optimal cut-off value of TD counts was 4, and the patients were classified into the TD0 (count = 0), TD1 (count = 1-3) and TD2 (count ≥ 4) groups accordingly. The estimated 5-year OS was significantly different among the three groups (69.4%, 95% CI 68.8%-70.0% in TD0; 60.5%, 95% CI 58.9%-62.2% in TD1 and 42.6%, 95% CI 39.2%-46.4% in TD2, respectively, p < 0.001). The coN system integrating LNM and TD was established, and patients with stage III colon cancer were reclassified into five subgroups (coN1a, coN1b, coN2a, coN2b and coN2c). Compared with conventional N staging, the coN staging Cox model had a smaller AIC (197097.581 vs. 197358.006) and a larger C-index (0.611 vs. 0.601). The AUCs of coN staging at 3, 5 and 7 years were also greater than those of conventional N staging (0.6305, 0.6326, 0.6314 vs. 0.6186, 0.6197, 0.6160). Concomitant with the SEER cohort results, the coN staging Cox model of the Xiangya cohort also had a smaller AIC (2883.856 vs. 2906.741) and a larger C-index (0.669 vs. 0.633). Greater AUCs at 3, 5 and 7 years for coN staging were also observed in the Xiangya cohort (0.6983, 0.6774, 0.6502 vs. 0.6512, 0.6368, 0.6199).
Not only the presence but also the number of TDs is associated with poor prognosis in stage III colon cancer. A combined N staging system integrating LNM and TD provides more accurate prognostic prediction than the latest AJCC N staging in stage III colon cancer.
尽管肿瘤沉积（TD）的起源和定义存在争议，但在结肠癌的肿瘤淋巴结转移（TNM）分期系统中，TD 的意义一直被低估，尤其是在 III 期患者中。我们旨在进一步证实 TD 在 III 期结肠癌中的预后价值，并建立一种更准确的“coN”分期系统，将 TD 与淋巴结转移（LNM）相结合。
回顾性收集 2010 年至 2017 年期间来自 Surveillance, Epidemiology and End Results（SEER）数据库的 III 期结肠癌患者的 TD 状态信息。使用 Cox 回归分析评估 TD 对预后的影响。使用最大选择秩统计选择 TD 计数的最佳截止值。通过 Akaike 信息准则（AIC）、Harrell 一致性指数（C-index）和时间依赖性接受者操作特征（ROC）曲线评估和比较传统 N 分期和新的 coN 分期的预测能力。收集 2014 年至 2018 年来自湘雅数据库的 III 期结肠癌患者的临床病理数据，以验证 coN 分期系统。
共纳入 39185 例 III 期结肠癌患者：SEER 队列 38446 例，湘雅队列 739 例。III 期结肠癌的 TD 发生率约为 30%（SEER 为 26%，湘雅数据库为 30%）。TD 与总生存期（OS）显著相关（HR=1.37，95%CI 1.31-1.44，p<0.001）。TD 计数的最佳截止值为 4，患者分为 TD0（计数=0）、TD1（计数=1-3）和 TD2（计数≥4）三组。三组之间的 5 年 OS 差异有统计学意义（TD0 组为 69.4%，95%CI 68.8%-70.0%；TD1 组为 60.5%，95%CI 58.9%-62.2%；TD2 组为 42.6%，95%CI 39.2%-46.4%，p<0.001）。建立了整合 LNM 和 TD 的 coN 系统，并将 III 期结肠癌患者重新分为五组（coN1a、coN1b、coN2a、coN2b 和 coN2c）。与传统 N 分期相比，coN 分期 Cox 模型的 AIC 更小（197097.581 vs. 197358.006），C-index 更大（0.611 vs. 0.601）。coN 分期在 3、5 和 7 年的 AUC 也大于传统 N 分期（0.6305、0.6326、0.6314 vs. 0.6186、0.6197、0.6160）。与 SEER 队列结果一致，湘雅队列的 coN 分期 Cox 模型的 AIC 也更小（2883.856 vs. 2906.741），C-index 更大（0.669 vs. 0.633）。coN 分期在 3、5 和 7 年的 AUC 也在湘雅队列中更大（0.6983、0.6774、0.6502 vs. 0.6512、0.6368、0.6199）。
TD 的存在和数量都与 III 期结肠癌的不良预后相关。整合 LNM 和 TD 的 N 分期系统比最新的 AJCC N 分期在 III 期结肠癌中提供了更准确的预后预测。
