Effect of Lymph Node Ratio on Prognosis of Stage Ⅲ Colorectal Cancer_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

 MENGXiang-jun , FANGChao , WANGCun , WUHao-yan ,  ZHOUZong-guang

Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China;

Corresponding author：

ZHOUZong-guang, Email: zhou767@163.com

Keywords：

Colorectal cancer; Number of lymph node; Lymph node ratio; Prognosis

DOI：

10.7507/1007-9424.20160346

Video：

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Objective To explore effect of lymph node ratio (LNR) on prognosis for patients with stage Ⅲ colorectal cancer. Methods The clinicopathologic data of 1 424 stage Ⅲ patients who underwent curative resection in this hospital from January 2009 to December 2013 were analyzed retrospectively. These patients were divided into low LNR group (LNR<optimal cut-off value) and high LNR group (LNR≥optimal cut-off value) according to the optimal cut-off value by receiver operating characteristic curve. The correlation between prognosis and clinicopathologic features was analyzed by using univariate analysis and Cox's proportional hazards regression model. The 5-year cumulative disease-free survival (DFS) and overall survival (OS) were calculated by using Kaplan-Meier method. Results The area under the receiver operating characteristic curve was 0.639, the optimal cut-off value of LNR was 0.267. The 5-year cumulative DFS and OS of the low LNR group were significantly higher than those of the high LNR group (DFS:53.8% versus 34.4%, P<0.001; OS:60.5% versus 44.5%, P<0.001). The results of univariate analysis showed that the preoperative carcinoembryonic antigen (CEA) level, degree of differentiation, TNM stage, pT stage, pN stage, vascular invasion, tumor diameter, and LNR were associated with the DFS and OS (P<0.05), but the number of lymph nodes retrieved was only associated with the DFS (P<0.05). The results of Cox analysis showed that the preoperative CEA level, degree of differentiation, TNM stage, and LNR were the independent prognostic factors for the DFS and OS (P<0.05), but the number of lymph nodes retrieved and the vascular invasion were only the independent prognostic factors for the DFS (P<0.05). Conclusion LNR is a prognostic factor in stage Ⅲ colorectal cancer, and it might be as a supplement for TNM staging system.

Citation： MENGXiang-jun, FANGChao, WANGCun, WUHao-yan, ZHOUZong-guang. Effect of Lymph Node Ratio on Prognosis of Stage Ⅲ Colorectal Cancer. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2016, 23(11): 1353-1357. doi: 10.7507/1007-9424.20160346 Copy

1.	Chen W, Zheng R, Baade PD, et al. Cancer statistics in China, 2015. CA Cancer J Clin, 2016, 66(2):115-132.
2.	Kotake K, Honjo S, Sugihara K, et al. Number of lymph nodes retrie-ved is an important determinant of survival of patients with stage Ⅱ and stage Ⅲ colorectal cancer. Jpn J Clin Oncol, 2012, 42(1):29-35.
3.	Resch A, Langner C. Lymph node staging in colorectal cancer:old controversies and recent advances. World J Gastroenterol, 2013, 19 (46):8515-8526.
4.	Cunningham D, Atkin W, Lenz HJ, et al. Colorectal cancer. Lancet, 2010, 375(9719):1030-1047.
5.	Sobin L, Gospodarowicz M, Wittekind C. TNM classification of malignant tumors. 7th ed. New York:Wiley, 2009.
6.	Edge SB, Byrd DR, Compton CC, et al, eds. AJCC Cancer Staging Manual. 7th ed. Chicago, IL:Springer, 2010.
7.	Park HC. Clinical significance of the metastatic lymph-node ratio in rectal cancer. Ann Coloproctol, 2013, 29(3):89-90.
8.	Makkai-Popa ST, Luncă S, Târcoveanu E, et al. Lymph node status assessed through the log odds ratio-a better tool in the prognosis of colorectal cancer relapse. Rom J Morphol Embryol, 2014, 55(1):97-102.
9.	Jiang K, Zhu Y, Liu Y, et al. Lymph node ratio as an independent prognostic indicator in stage Ⅲ colorectal cancer:especially for fewer than 12 lymph nodes examined. Tumour Biol, 2014, 35(11):11685-11690.
10.	Wong SL, Ji H, Hollenbeck BK, et al. Hospital lymph node examina-tion rates and survival after resection for colon cancer. JAMA, 2007, 298(18):2149-2154.
11.	Evans MD, Barton K, Rees A, et al. The impact of surgeon and patho-logist on lymph node retrieval in colorectal cancer and its impact on survival for patients with Dukes, stage B disease. Colorectal Dis, 2008, 10(2):157-164.
12.	Nelen SD, van Steenbergen LN, Dassen AE, et al. The lymph node ratio as a prognostic factor for gastric cancer. Acta Oncol, 2013, 52 (8):1751-1759.
13.	Liu D, Chen Y, Deng M, et al. Lymph node ratio and breast cancer prognosis:a meta-analysis. Breast Cancer, 2014, 21(1):1-9.
14.	Yamamoto Y, Ikoma H, Morimura R, et al. The clinical impact of the lymph node ratio as a prognostic factor after resection of pancreatic cancer. Anticancer Res, 2014, 34(5):2389-2394.
15.	Berger AC, Sigurdson ER, LeVoyer T, et al. Colon cancer survival is associated with decreasing ratio of metastatic to examined lymph nodes. J Clin Oncol, 2005, 23(34):8706-8712.
16.	任镜清, 薛福龙, 刘少杰, 等. 淋巴结转移度及肿瘤N分期对Ⅲ期结直肠癌复发或转移的预测价值. 中华胃肠外科杂志, 2015, 18(6):553-557.
17.	Rausei S, Iovino D, Tenconi S, et al. Impact of lymph node ratio on survival of colorectal cancer patients. Int J Surg, 2013, 11 Suppl 1:S95-S99.
18.	Ceelen W, Van Nieuwenhove Y, Pattyn P, et al. Prognostic value of the lymph node ratio in stage Ⅲ colorectal cancer:a systematic review. Ann Surg Oncol, 2010, 17(11):2847-2855.
19.	Edler D, Ohrling K, Hallström M, et al. The number of analyzed lymph nodes-a prognostic factor in colorectal cancer. Acta Oncol, 2007, 46(7):975-981.
20.	Kim YW, Kim NK, Min BS, et al. The influence of the number of retrieved lymph nodes on staging and survival in patients with stage Ⅱ and Ⅲ rectal cancer undergoing tumor-specific mesorectal excision. Ann Surg, 2009, 249(6):965-972.
21.	Sugimoto K, Sakamoto K, Tomiki Y, et al. Proposal of new classifica-tion for stage Ⅲ colon cancer based on the lymph node ratio:analy-sis of 4 172 patients from multi-institutional database in Japan. Ann Surg Oncol, 2015, 22(2):528-534.
22.	Kobayashi H, Mochizuki H, Kato T, et al. Lymph node ratio is a powerful prognostic index in patients with stage Ⅲ distal rectal cancer:a Japanese multicenter study. Int J Colorectal Dis, 2011, 26(7):891-896.
23.	Sugimoto K, Sakamoto K, Tomiki Y, et al. The validity of predicting prognosis by the lymph node ratio in node-positive colon cancer. Dig Surg, 2013, 30(4-6):368-374.
24.	Schiffmann L, Eiken AK, Gock M, et al. Is the lymph node ratio superior to the Union for International Cancer Control (UICC) TNM system in prognosis of colon cancer? World J Surg Oncol, 2013, 11:79.
25.	Priolli DG, Cardinalli IA, Pereira JA, et al. Metastatic lymph node ratio as an independent prognostic variable in colorectal cancer:study of 113 patients. Tech Coloproctol, 2009, 13(2):113-121.

1. Chen W, Zheng R, Baade PD, et al. Cancer statistics in China, 2015. CA Cancer J Clin, 2016, 66(2):115-132.
2. Kotake K, Honjo S, Sugihara K, et al. Number of lymph nodes retrie-ved is an important determinant of survival of patients with stage Ⅱ and stage Ⅲ colorectal cancer. Jpn J Clin Oncol, 2012, 42(1):29-35.
3. Resch A, Langner C. Lymph node staging in colorectal cancer:old controversies and recent advances. World J Gastroenterol, 2013, 19 (46):8515-8526.
4. Cunningham D, Atkin W, Lenz HJ, et al. Colorectal cancer. Lancet, 2010, 375(9719):1030-1047.
5. Sobin L, Gospodarowicz M, Wittekind C. TNM classification of malignant tumors. 7th ed. New York:Wiley, 2009.
6. Edge SB, Byrd DR, Compton CC, et al, eds. AJCC Cancer Staging Manual. 7th ed. Chicago, IL:Springer, 2010.
7. Park HC. Clinical significance of the metastatic lymph-node ratio in rectal cancer. Ann Coloproctol, 2013, 29(3):89-90.
8. Makkai-Popa ST, Luncă S, Târcoveanu E, et al. Lymph node status assessed through the log odds ratio-a better tool in the prognosis of colorectal cancer relapse. Rom J Morphol Embryol, 2014, 55(1):97-102.
9. Jiang K, Zhu Y, Liu Y, et al. Lymph node ratio as an independent prognostic indicator in stage Ⅲ colorectal cancer:especially for fewer than 12 lymph nodes examined. Tumour Biol, 2014, 35(11):11685-11690.
10. Wong SL, Ji H, Hollenbeck BK, et al. Hospital lymph node examina-tion rates and survival after resection for colon cancer. JAMA, 2007, 298(18):2149-2154.
11. Evans MD, Barton K, Rees A, et al. The impact of surgeon and patho-logist on lymph node retrieval in colorectal cancer and its impact on survival for patients with Dukes, stage B disease. Colorectal Dis, 2008, 10(2):157-164.
12. Nelen SD, van Steenbergen LN, Dassen AE, et al. The lymph node ratio as a prognostic factor for gastric cancer. Acta Oncol, 2013, 52 (8):1751-1759.
13. Liu D, Chen Y, Deng M, et al. Lymph node ratio and breast cancer prognosis:a meta-analysis. Breast Cancer, 2014, 21(1):1-9.
14. Yamamoto Y, Ikoma H, Morimura R, et al. The clinical impact of the lymph node ratio as a prognostic factor after resection of pancreatic cancer. Anticancer Res, 2014, 34(5):2389-2394.
15. Berger AC, Sigurdson ER, LeVoyer T, et al. Colon cancer survival is associated with decreasing ratio of metastatic to examined lymph nodes. J Clin Oncol, 2005, 23(34):8706-8712.
16. 任镜清, 薛福龙, 刘少杰, 等. 淋巴结转移度及肿瘤N分期对Ⅲ期结直肠癌复发或转移的预测价值. 中华胃肠外科杂志, 2015, 18(6):553-557.
17. Rausei S, Iovino D, Tenconi S, et al. Impact of lymph node ratio on survival of colorectal cancer patients. Int J Surg, 2013, 11 Suppl 1:S95-S99.
18. Ceelen W, Van Nieuwenhove Y, Pattyn P, et al. Prognostic value of the lymph node ratio in stage Ⅲ colorectal cancer:a systematic review. Ann Surg Oncol, 2010, 17(11):2847-2855.
19. Edler D, Ohrling K, Hallström M, et al. The number of analyzed lymph nodes-a prognostic factor in colorectal cancer. Acta Oncol, 2007, 46(7):975-981.
20. Kim YW, Kim NK, Min BS, et al. The influence of the number of retrieved lymph nodes on staging and survival in patients with stage Ⅱ and Ⅲ rectal cancer undergoing tumor-specific mesorectal excision. Ann Surg, 2009, 249(6):965-972.
21. Sugimoto K, Sakamoto K, Tomiki Y, et al. Proposal of new classifica-tion for stage Ⅲ colon cancer based on the lymph node ratio:analy-sis of 4 172 patients from multi-institutional database in Japan. Ann Surg Oncol, 2015, 22(2):528-534.
22. Kobayashi H, Mochizuki H, Kato T, et al. Lymph node ratio is a powerful prognostic index in patients with stage Ⅲ distal rectal cancer:a Japanese multicenter study. Int J Colorectal Dis, 2011, 26(7):891-896.
23. Sugimoto K, Sakamoto K, Tomiki Y, et al. The validity of predicting prognosis by the lymph node ratio in node-positive colon cancer. Dig Surg, 2013, 30(4-6):368-374.
24. Schiffmann L, Eiken AK, Gock M, et al. Is the lymph node ratio superior to the Union for International Cancer Control (UICC) TNM system in prognosis of colon cancer? World J Surg Oncol, 2013, 11:79.
25. Priolli DG, Cardinalli IA, Pereira JA, et al. Metastatic lymph node ratio as an independent prognostic variable in colorectal cancer:study of 113 patients. Tech Coloproctol, 2009, 13(2):113-121.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Effect of Lymph Node Ratio on Prognosis of Stage Ⅲ Colorectal Cancer

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