The new 'coN' staging system combining lymph node metastasis and tumour deposit provides a more accurate prognosis for TNM stage III colon cancer.
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.
Wang X
，Cheng W
，Dou X
，Tan F
，Yan S
，Zhou Z
，Li Y
，Xu B
，Liu C
，Ge H
，Tian M
，Liu F
，Li L
，Zhang S
，Li Q
，Pei H
，Pei Q
... -
《Cancer Medicine》
Combining tumor deposits with the number of lymph node metastases to improve the prognostic accuracy in stage III colon cancer: a post hoc analysis of the CALGB/SWOG 80702 phase III study (Alliance)(☆).
In colon cancer, tumor deposits (TD) are considered in assigning prognosis and staging only in the absence of lymph node metastasis (i.e. stage III pN1c tumors). We aimed to evaluate the prognostic value of the presence and the number of TD in patients with stage III, node-positive colon cancer.
All participants from the CALGB/SWOG 80702 phase III trial were included in this post hoc analysis. Pathology reports were reviewed for the presence and the number of TD, lymphovascular and perineural invasion. Associations with disease-free survival (DFS) and overall survival (OS) were evaluated by multivariable Cox models adjusting for sex, treatment arm, T-stage, N-stage, lymphovascular invasion, perineural invasion and lymph node ratio.
Overall, 2028 patients were included with 524 (26%) TD-positive and 1504 (74%) TD-negative tumors. Of the TD-positive patients, 80 (15.4%) were node negative (i.e. pN1c), 239 (46.1%) were pN1a/b (<4 positive lymph nodes) and 200 (38.5%) were pN2 (≥4 positive lymph nodes). The presence of TD was associated with poorer DFS [adjusted hazard ratio (aHR) = 1.63, 95% CI 1.33-1.98] and OS (aHR = 1.59, 95% CI 1.24-2.04). The negative effect of TD was observed for both pN1a/b and pN2 groups. Among TD-positive patients, the number of TD had a linear negative effect on DFS and OS. Combining TD and the number of lymph node metastases, 104 of 1470 (7.1%) pN1 patients were re-staged as pN2, with worse outcomes than patients confirmed as pN1 (3-year DFS rate: 65.4% versus 80.5%, P = 0.0003; 5-year OS rate: 87.9% versus 69.1%, P = <0.0001). DFS was not different between patients re-staged as pN2 and those initially staged as pN2 (3-year DFS rate: 65.4% versus 62.3%, P = 0.4895).
Combining the number of TD and the number of lymph node metastases improved the prognostication accuracy of tumor-node-metastasis (TNM) staging.
Cohen R
，Shi Q
，Meyers J
，Jin Z
，Svrcek M
，Fuchs C
，Couture F
，Kuebler P
，Ciombor KK
，Bendell J
，De Jesus-Acosta A
，Kumar P
，Lewis D
，Tan B
，Bertagnolli MM
，Philip P
，Blanke C
，O'Reilly EM
，Shields A
，Meyerhardt JA
... -
《-》
Prognostic Significance of Tumor Deposits in Patients With Stage III Colon Cancer: A Nomogram Study.
The clinical characteristics of stage III colon cancer and the prognostic significance of tumor deposits were investigated, to construct a prognostic nomogram.
The data of patients were retrieved from the Surveillance, Epidemiology, and End Results database. Patients were randomized to a training or validation cohort. The Kaplan-Meier method was used to analyze survival rates. In the training cohort, a prognostic nomogram was established via Cox regression and then tested in the validation cohort. The accuracy and discrimination of the nomogram were assessed using concordance indices (C-indices) and calibration curves.
Of the 9246 patients meeting the inclusion criteria, 1788 (19.3%) had tumor deposits. Patients with tumor deposits only showed similar survival rates to those with lymph node metastases only (P = 0.83). Compared with these, patients with both tumor deposits and lymph node metastases exhibited significantly worse survival (P < 0.01). In the multivariate Cox regression analyses, the following were identified as independent prognostic indicators and adopted to formulate the nomogram: tumor deposits, age, ethnicity, T stage, the number of positive regional lymph nodes, grade, and carcinoembryonic antigen. In the training cohort, the calibration curve showed good consistency, and the concordance index of the nomogram for predicting overall survival reaches 0.727 (95% CI: 0.71524-0.73876), superior to the concordance index of the American Joint Committee on Cancer staging system (0.594, 95% CI: 0.58224-0.60576). These results are supported in the validation cohort.
Tumor deposits may be an independent prognostic factor for patients with stage III colon cancer after colectomy. The nomogram constructed herein accurately predicted overall survival.
Zheng P
，Chen Q
，Li J
，Jin C
，Kang L
，Chen D
... -
《-》
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