A Prognostic Model To Predict Survival In Stage III Colon Cancer Patients Based on Histological Grade, Preoperative Carcinoembryonic Antigen Level and the Neutrophil Lymphocyte Ratio

  • Wuxiao, Zhi-Jun ;
  • Zhou, Hai-Yan ;
  • Wang, Ke-Feng ;
  • Chen, Xiao-Qin ;
  • Hao, Xin-Bao ;
  • Lu, Yan-Da ;
  • Xia, Zhong-Jun
  • Published : 2015.02.25


Background: Stage III colon cancer patients demonstrate diverse clinical outcomes. The aim of this study was to develop a prognostic model in order to better predict their survival. Materials and Methods: From 2004 to 2010, 548 patients were retrospectively analyzed, among whom 328 were defined as the study group and the remaining 220 served as a validation group. Clinico-pathologic features, including age, gender, histological grade, T stage, number of positive lymph nodes, number of harvest lymph nodes, pretreatment carcinoembryonic antigen (CEA) levels and pretreatment neutrophil lymphocyte ratio (NLR), were collected. Kaplan-Meier survival curves were used to detect prognostic factors and multivariate analysis was applied to identify independent examples on which to develop a prognostic model. Finally, the model was further validated with the validation group. Results: Histological grade (p=0.002), T stage (p=0.011), number of positive lymph nodes (p=0.003), number of harvested lymph nodes (p=0.020), CEA (p=0.005), and NLR (p<0.001) were found as prognostic factors while histological grade [RR(relative risk):0.632, 95%CI (Confidence interval) 0.405~0.985, p=0.043], CEA (RR:0.644, 95%CI:0.431~0.964, p=0.033) and NLR (RR:0.384, 95%CI:0.255~0.580, p<0.001) levels were independent. The prognostic model based on these three factors was able to classify patients into high risk, intermediate and low risk groups (p<0.001), both in study and validation groups. Conclusions: Histological grade, pretreatment CEA and NLR levels are independent prognostic factors in stage III colon cancer patients. A prognostic model based on these factors merits attention in future clinical practice.


NLR;CEA;colon cancer;biomarker;prognosis;model


  1. Adlard JW, Richman SD, Seymour MT, et al (2002). Prediction of the response of colorectal cancer to systemic therapy. Lancet Oncol, 3, 75-82.
  2. Al Murri AM, Wilson C, Lannigan A, et al (2007). Evaluation of the relationship between the systemic inflammatory response and cancer-specific survival in patients with primary operable breast cancer. Br J Cancer, 96, 891-5.
  3. Alberts SR, Sargent DJ, Nair S, et al (2012). Effect of oxaliplatin, fluorouracil, and leucovorin with or without cetuximab on survival among patients with resected stage III colon cancer: a randomized trial. JAMA, 307, 1383-93.
  4. Allegra CJ, Yothers G, O'Connell MJ, et al (2011). Phase III trial assessing bevacizumab in stages II and III carcinoma of the colon: results of NSABP protocol C-08. J Clin Oncol, 29, 11-6.
  5. Barton MK (2012). Oxaliplatin in the adjuvant treatment of colon cancer. CA Cancer J Clin, 62, 3-4.
  6. Belt EJ, Brosens RP, Delis-van Diemen PM, et al (2012). Cell cycle proteins predict recurrence in stage II and III colon cancer. Ann Surg Oncol, 19, 682-92.
  7. Bertagnolli MM, Niedzwiecki D, Compton CC, et al (2009). Microsatellite instability predicts improved response to adjuvant therapy with irinotecan, fluorouracil, and leucovorin in stage III colon cancer: Cancer and Leukemia Group B Protocol 89803. J Clin Oncol, 27, 1814-21.
  8. Cassidy J, Clarke S, Diaz-Rubio E, et al (2008). Randomized phase III study of capecitabine plus oxaliplatin compared with fluorouracil/folinic acid plus oxaliplatin as first-line therapy for metastatic colorectal cancer. J Clin Oncol, 26, 2006-12.
  9. Cedres S, Torrejon D, Martinez A, et al (2012). Neutrophil to lymphocyte ratio (NLR) as an indicator of poor prognosis in stage IV non-small cell lung cancer. Clin Transl Oncol, 14, 864-9.
  10. Chiang SF, Hung HY, Tang R, et al (2012). Can neutrophil-tolymphocyte ratio predict the survival of colorectal cancer patients who have received curative surgery electively? Int J Colorectal Dis, 27, 1347-57.
  11. Chua W, Charles KA, Baracos VE, et al (2011). Neutrophil/lymphocyte ratio predicts chemotherapy outcomes in patients with advanced colorectal cancer. Br J Cancer, 10, 1288-95.
  12. Ferradini L, Miescher S, Stoeck M, et al (1991). Cytotoxic potential despite impaired activation pathways in T lymphocytes infiltrating nasopharyngeal carcinoma. Int J Cancer, 47, 362-70
  13. Giraldez MD, Lozano JJ, Cuatrecasas M, et al (2013). Geneexpression signature of tumor recurrence in patients with stage II and III colon cancer treated with 5'fluoruracil-based adjuvant chemotherapy. Int J Cancer. 132, 1090-7
  14. Gunnarsson H, Holm T, Ekholm A, et al (2011). Emergency presentation of colon cancer is most frequent during summer. Colorectal Dis, 13, 663-8.
  15. Halazun KJ, Hardy MA, Rana AA, et al (2009). Negative impact of neutrophil-lymphocyte ratio on outcome after liver transplantation for hepatocellular carcinoma. Ann Surg, 250, 141-51.
  16. Hanahan D, Weinberg RA (2000). The hallmarks of cancer. Cell, 100, 57-70.
  17. Hanahan D, Weinberg RA (2011). Hallmarks of cancer: the next generation. Cell, 144, 646-74.
  18. Kuebler JP, Wieand HS, O'Connell MJ, et al (2007). Oxaliplatin combined with weekly bolus fluorouracil and leucovorin as surgical adjuvant chemotherapy for stage II and III colon cancer: results from NSABP C-07. J Clin Oncol, 25, 2198-204.
  19. Kwon HC, Kim SH, Oh SY, et al (2012). Clinical significance of preoperative neutrophil-lymphocyte versus plateletlymphocyte ratio in patients with operable colorectal cancer. Biomarkers, 17, 216-22.
  20. Ma CJ, Hsieh JS, Wang WM, et al (2006). Multivariate analysis of prognostic determinants for colorectal cancer patients with high preoperative serum CEA levels: prognostic value of postoperative serum CEA levels. Kaohsiung J Med Sci, 22, 604-9.
  21. Mallappa S, Sinha A, Gupta S, et al (2013). Preoperative neutrophil lymphocyte ratio greater than five is a prognostic factor for recurrent colorectal cancer. Colorectal Dis, 15, 323-8
  22. Moertel CG, Fleming TR, Macdonald JS, et al (1990). Levamisole and fluorouracil for adjuvant therapy of resected colon carcinoma. N Engl J Med, 322, 352-8.
  23. O'Connell JB, Maggard MA, Ko CY (2004). Colon cancer survival rates with the new American Joint Committee on Cancer sixth edition staging. J Natl Cancer Inst, 96, 1420-5.
  24. Ogino S, Meyerhardt JA, Irahara N, et al (2009). KRAS mutation in stage III colon cancer and clinical outcome following intergroup trial CALGB 89803. Clin Cancer Res, 15, 7322-9.
  25. Ogino S, Shima K, Meyerhardt JA, et al (2012). Predictive and prognostic roles of BRAF mutation in stage III colon cancer: results from intergroup trial CALGB 89803. Clin Cancer Res, 18, 890-900.
  26. Peng Y, Wang L, Gu J, et al (2013). Elevated preoperative carcinoembryonic antigen (CEA) and Ki67 is predictor of decreased survival in IIA stage colon cancer. World J Surg, 37, 208-13
  27. Qiu HB, Zhang LY, Li YF, et al (2011). Ratio of metastatic to resected lymph nodes enhances to predict survival in patients with stage III colorectal cancer. Ann Surg Oncol, 18, 1568-74.
  28. Takagawa R, Fujii S, Ohta M, et al (2008). Preoperative serum carcinoembryonic antigen level as a predictive factor of recurrence after curative resection of colorectal cancer. Ann Surg Oncol, 15, 3433-9.
  29. Wong JC, Chan SK, Schaeffer DF, et al (2011). Absence of MMP2 expression correlates with poor clinical outcomes in rectal cancer, and is distinct from MMP1-related outcomes in colon cancer. Clin Cancer Res, 17, 4167-76.

Cited by

  1. Smoking at diagnosis significantly decreases 5-year cancer-specific survival in a population-based cohort of 18 166 colon cancer patients vol.45, pp.6, 2017,
  2. Clinical significance of changes in systemic inflammatory markers and carcinoembryonic antigen levels in predicting metastatic colorectal cancer prognosis and chemotherapy response pp.17437555, 2017,