Carcinoembryonic Antigen as a Prognostic Factor in Colorectal Cancer with Liver Metastases
Affiliation(s)
1 College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK. 2 Department of Hepatobiliary and Pancreatic Surgery, University Hospitals of Leicester, Leicester, UK. 3 Department of Surgery, Centro Medico de San Isidro, Buenos Aires, Argentina.
1 College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK. 2 Department of Hepatobiliary and Pancreatic Surgery, University Hospitals of Leicester, Leicester, UK. 3 Department of Surgery, Centro Medico de San Isidro, Buenos Aires, Argentina.
ABSTRACT
Aim: The objective of this study was to investigate the prognostic value of serum carcinoembryonic antigen (CEA) level in colorectal cancer patients with liver metastases. The serum CEA level was recorded at the point of metastasis diagnosis, differing from the majority of literature looking at preoperative metastasectomy CEA level. Methods: From January 2010 to December 2014, 138 patients with a diagnosis of colorectal cancer and liver metastases were included in the study—population from Buenos Aires, Argentina. Patients with both resectable and unresectable liver metastases were followed up over a 4-year period. Kaplan Meier survival analysis was used to produce survival curves that were compared by log-rank test. Results: The overall survival for all patients studied with a CEA < 100 ng/ml was significantly longer compared to patients with CEA ≥ 100 ng/mL (p < 0.001). The 1-, 2-, and 3-year overall survival rates for the whole cohort were 73.6, 56.6 and 53.8% respectively. For patients with unresectable metastases, a low CEA level (<100 ng/mL) was also associated with the increased overall survival (p = 0.036). Conclusions: In our patient cohort, this study indicated that a low CEA level (<100 ng/mL) measured at metastasis diagnosis was a good prognostic indicator for improving survival in patients with colorectal liver metastases. These findings highlight the importance of measuring serum CEA levels in this group of patients at the time of liver metastasis diagnosis.
Aim: The objective of this study was to investigate the prognostic value of serum carcinoembryonic antigen (CEA) level in colorectal cancer patients with liver metastases. The serum CEA level was recorded at the point of metastasis diagnosis, differing from the majority of literature looking at preoperative metastasectomy CEA level. Methods: From January 2010 to December 2014, 138 patients with a diagnosis of colorectal cancer and liver metastases were included in the study—population from Buenos Aires, Argentina. Patients with both resectable and unresectable liver metastases were followed up over a 4-year period. Kaplan Meier survival analysis was used to produce survival curves that were compared by log-rank test. Results: The overall survival for all patients studied with a CEA < 100 ng/ml was significantly longer compared to patients with CEA ≥ 100 ng/mL (p < 0.001). The 1-, 2-, and 3-year overall survival rates for the whole cohort were 73.6, 56.6 and 53.8% respectively. For patients with unresectable metastases, a low CEA level (<100 ng/mL) was also associated with the increased overall survival (p = 0.036). Conclusions: In our patient cohort, this study indicated that a low CEA level (<100 ng/mL) measured at metastasis diagnosis was a good prognostic indicator for improving survival in patients with colorectal liver metastases. These findings highlight the importance of measuring serum CEA levels in this group of patients at the time of liver metastasis diagnosis.
KEYWORDS
Carcinoembryonic Antigen (CEA), Colorectal Cancer Survival, Liver Metastasis, Postoperative Mortality
Carcinoembryonic Antigen (CEA), Colorectal Cancer Survival, Liver Metastasis, Postoperative Mortality
Cite this paper
McNally, G. , Lloyd, D. and Grondona, J. (2015) Carcinoembryonic Antigen as a Prognostic Factor in Colorectal Cancer with Liver Metastases. Journal of Cancer Therapy, 6, 1035-1044. doi: 10.4236/jct.2015.612113.
McNally, G. , Lloyd, D. and Grondona, J. (2015) Carcinoembryonic Antigen as a Prognostic Factor in Colorectal Cancer with Liver Metastases. Journal of Cancer Therapy, 6, 1035-1044. doi: 10.4236/jct.2015.612113.
References
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http://dx.doi.org/10.1055/s-0029-1242458 [2] Khatri, V.P., et al. (2005) Extending the Frontiers of Surgical Therapy for Hepatic Colorectal Metastases: Is There A Limit? Journal of Clinical Oncology, 23, 8490-8499.
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http://dx.doi.org/10.1097/sla.0b013e31815aa2c2 [6] Folprecht, G., et al. (2005) Neoadjuvant Treatment of Unresectable Colorectal Liver Metastases: Correlation between Tumour Response and Resection Rates. Annals of Oncology, 16, 13311-1319.
http://dx.doi.org/10.1093/annonc/mdi246 [7] Chung, K.Y., et al. (2005) Antibody-Based Therapeutics for Colorectal Cancer. Oncologist, 10, 701-709.
http://dx.doi.org/10.1634/theoncologist.10-9-701 [8] Wanebo, H.J., Rao, B., Pinsky, C.M., Hoffman, R.G., Stearns, M., Schwartz, M.K. and Oettgen, H.F. (1978) Preoperative Carcinoembryonic Antigen Level as a Prognostic Indicator in Colorectal Cancer. The New England Journal of Medicine, 299, 448-451.
http://dx.doi.org/10.1056/NEJM197808312990904 [9] Moertel, C.G., O’Fallon, J.R., Go, V.L., O’Connell, M.J. and Thynne, G.S. (1986) The Preoperative Carcinoembryonic Antigen Test in the Diagnosis, Staging, and Prognosis of Colorectal Cancer. Cancer, 58, 603-610.
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http://dx.doi.org/10.1097/sla.0b013e3180603039 [18] Kishi, Y., Kopetz, S., Chun, Y.S., Palavecino, M., Abdalla, E.K. and Vauthey, J.-N. (2009) Blood Neutrophil-to-Lymphocyte Ratio Predicts Survival in Patients with Colorectal Liver Metastases Treated with Systemic Chemotherapy. Annals of Surgical Oncology, 16, 614-622.
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http://dx.doi.org/10.1159/000354310 [22] Marti, J., Modolo, M.M., Fuster, J., Comas, J., Cosa, R., Ferrer, J., et al. (2009) Prognostic Factors and Time-Related Changes Influence Results of Colorectal Liver Metastases Surgical Treatment: A Single-Center Analysis. World Journal of Gastroenterology, 15, 2587-2594.
http://dx.doi.org/10.3748/wjg.15.2587 [23] Donadon, M., Ribero, D., Morris-Stiff, G., Abdalla, E.K. and Vauthey, J.N. (2007) New Paradigm in the Management of Liver-Only Metastases from Colorectal Cancer. Gastrointestinal Cancer Research, 1, 20-27. [24] Aloia, T.A., Vauthey, J.N., Loyer, E.M., Ribero, D., Pawlik, T.M., Wei, S.H., et al. (2006) Solitary Colorectal Liver Metastasis: Resection Determines Outcome. Archives of Surgery, 141, 460-466.
http://dx.doi.org/10.1001/archsurg.141.5.460 [25] Fernandez, F.G., Drebin, J.A., Linehan, D.C., Dehdashti, F., Siegel, B.A. and Strasberg, S.M. (2004) Five-Year Survival after Resection of Hepatic Metastases from Colorectal Cancer in Patients Screened by Positron Emission Tomography with F-18 Fluorodeoxyglucose (FDG-PET). Annals of Surgery, 240, 438-447.
http://dx.doi.org/10.1097/01.sla.0000138076.72547.b1 [26] Lee, W.S., Yun, S.H., Chun, H.K., Lee, W.Y., Kim, S.J., Choi, S.H., et al. (2008) Clinical Outcomes of Hepatic Resection and Radiofrequency Ablation in Patients with Solitary Colorectal Liver Metastasis. Journal of Clinical Gastroenterology, 42, 945-949.
http://dx.doi.org/10.1097/MCG.0b013e318064e752 [27] Lordan, J.T., Riga, A., Worthington, T.R. and Karanjia, N.D. (2009) Early and Long-Term Outcomes of Patients Undergoing Liver Resection and Diaphragm Excision for Advanced Colorectal Liver Metastases. Annals of The Royal College of Surgeons of England, 91, 483-488.
http://dx.doi.org/10.1308/rcsann.2009.91.6.483 [28] Nikfarjam, M., Shereef, S., Kimchi, E.T., Gusani, N.J., Jiang, Y.X., Avella, D.M., et al. (2009) Survival Outcomes of Patients with Colorectal Liver Metastases Following Hepatic Resection or Ablation in the Era of Effective Chemotherapy. Annals of Surgical Oncology, 16, 1860-1867.
http://dx.doi.org/10.1245/s10434-008-0225-3 [29] Choti, M.A., Sitzmann, J.V., Tiburi, M.F., Sumetchotimetha, W., Rangsin, R., Schulick, R.D., et al. (2002) Trends in Long-Term Survival Following Liver Resection for Hepatic Colorectal Metastases. Annals of Surgery, 235, 759-766.
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[1] Haggar, F.A. and Boushey, R.P. (2009) Colorectal Cancer Epidemiology: Incidence, Mortality, Survival, and Risk Factors. Clinics in Colon and Rectal Surgery, 22, 191-197.
http://dx.doi.org/10.1055/s-0029-1242458 [2] Khatri, V.P., et al. (2005) Extending the Frontiers of Surgical Therapy for Hepatic Colorectal Metastases: Is There A Limit? Journal of Clinical Oncology, 23, 8490-8499.
http://dx.doi.org/10.1200/JCO.2004.00.6155 [3] Benson, A.B., et al. (2007) Epidemiology, Disease Progression, and Economic Burden of Colorectal Cancer. Journal of Managed Care Pharmacy, 13, S5-S18. [4] Fong, Y., et al. (1999) Clinical Score for Predicting Recurrence after Hepatic Resection for Metastatic Colorectal Cancer: Analysis of 1001 Consecutive Cases. Annals of Surgery, 230, 209-321.
http://dx.doi.org/10.1097/00000658-199909000-00004 [5] Rees, M., et al. (2008) Evaluation of Long-Term Survival after Hepatic Resection for Metastatic Colorectal Cancer: A Multifactorial Model of 929 Patients. Annals of Surgery, 247, 25-135.
http://dx.doi.org/10.1097/sla.0b013e31815aa2c2 [6] Folprecht, G., et al. (2005) Neoadjuvant Treatment of Unresectable Colorectal Liver Metastases: Correlation between Tumour Response and Resection Rates. Annals of Oncology, 16, 13311-1319.
http://dx.doi.org/10.1093/annonc/mdi246 [7] Chung, K.Y., et al. (2005) Antibody-Based Therapeutics for Colorectal Cancer. Oncologist, 10, 701-709.
http://dx.doi.org/10.1634/theoncologist.10-9-701 [8] Wanebo, H.J., Rao, B., Pinsky, C.M., Hoffman, R.G., Stearns, M., Schwartz, M.K. and Oettgen, H.F. (1978) Preoperative Carcinoembryonic Antigen Level as a Prognostic Indicator in Colorectal Cancer. The New England Journal of Medicine, 299, 448-451.
http://dx.doi.org/10.1056/NEJM197808312990904 [9] Moertel, C.G., O’Fallon, J.R., Go, V.L., O’Connell, M.J. and Thynne, G.S. (1986) The Preoperative Carcinoembryonic Antigen Test in the Diagnosis, Staging, and Prognosis of Colorectal Cancer. Cancer, 58, 603-610.
http://dx.doi.org/10.1002/1097-0142(19860801)58:3<603::AID-CNCR2820580302>3.0.CO;2-K [10] Zamcheck, N. (1975) The Present Status of CEA in Diagnosis, Prognosis, and Evaluation of Therapy. Cancer, 36, 2460-2468.
http://dx.doi.org/10.1002/1097-0142(197512)36:6<2460::AID-CNCR2820360631>3.0.CO;2-6 [11] Mann, C.D., Metcalfe, M.S., Leopardi, L.N. and Maddern, G.J. (2004) The Clinical Risk Score: Emerging as a Reliable Preoperative Prognostic Index in Hepatectomy for Colorectal Metastases. Archives of Surgery, 139, 1168-1172.
http://dx.doi.org/10.1001/archsurg.139.11.1168 [12] Abbas, S., Lam, V. and Hollands, M. (2011) Ten-Year Survival after Liver Esection for Colorectal Metastases: Systematic Review and Meta-Analysis. ISRN Oncology, 2011, Article ID: 763245.
http://dx.doi.org/10.5402/2011/763245 [13] Kanas, G., Taylor, A., Primrose, J.N., Langeberg, W.J., Kelsh, M.A., Mowat, F.S., et al. (2012) Survival after Liver Resection in Metastatic Colorectal Cancer: Review and Meta-Analysis of Prognostic Factors. Clinical Epidemiology, 4, 283-301. [14] Wang, Y., Liu, Y.F., Cheng, Y., Yi, D.H., Li, P., Song, W.Q., Fu, D.Z. and Wang, X. (2010) Prognosis of Colorectal Cancer with Liver Metastasis: Value of a Prognostic Index. Brazilian Journal of Medical and Biological Research, 43, 1116-1122.
http://dx.doi.org/10.1590/S0100-879X2010007500103 [15] Charnsangavej, C., Clary, B., Fong, Y., Grothey, A., Pawlik, T.M. and Choti, M.A. (2006) Selection of Patients for Resection of Hepatic Colorectal Metastases: Expert Consensus Statement. Annals of Surgical Oncology, 13, 1261-1268.
http://dx.doi.org/10.1245/s10434-006-9023-y [16] Malik, H.Z., Prasad, R., Halazun, K.J., Aldoori, A., Al-Mukhtar, A., Gomez, D., et al. (2007) Preoperative Prognostic Score for Predicting Survival after Hepatic Resection for Colorectal Liver Metastases. Annals of Surgery, 246, 806-814.
http://dx.doi.org/10.1097/SLA.0b013e318142d964 [17] Zakaria, S., Donohue, J.H., Que, F.G., Farnell, M.B., Schleck, C.D., Ilstrup, D.M. and Nagorney, D.M. (2007) Hepatic Resection for Colorectal Metastases: Value for Risk Scoring Systems? Annals of Surgery, 246, 183-191.
http://dx.doi.org/10.1097/sla.0b013e3180603039 [18] Kishi, Y., Kopetz, S., Chun, Y.S., Palavecino, M., Abdalla, E.K. and Vauthey, J.-N. (2009) Blood Neutrophil-to-Lymphocyte Ratio Predicts Survival in Patients with Colorectal Liver Metastases Treated with Systemic Chemotherapy. Annals of Surgical Oncology, 16, 614-622.
http://dx.doi.org/10.1245/s10434-008-0267-6 [19] Mitsuyama, Y., Shiba, H., Haruki, K., Fujiwara, Y., Furukawa, K., Iida, T., et al. (2012) Carcinoembryonic Antigen and Carbohydrate Antigen 19-9 Are Prognostic Predictors of Colorectal Cancer with Unresectable Liver Metastasis. Oncology Letters, 3, 767-771. [20] Nagakura, S., Shirai, Y., Yokoyama, N., Wakai, T., Suda, T. and Hatakeyama, K. (2003) Major Hepatic Resection Reduces the Probability of Intrahepatic Recurrences Following Resection of Colorectal Carcinoma Liver Metastases. Hepatogastroenterology, 50, 779-783. [21] John, S.K., Robinson, S.M., Rehman, S., Harrison, B., Vallance, A., French, J.J., et al. (2013) prognostic Factors and Survival after Resection of Colorectal Liver Metastasis in the Era of Preoperative Chemotherapy: An 11-Year Single-Centre Study. Digestive Surgery, 30, 293-301.
http://dx.doi.org/10.1159/000354310 [22] Marti, J., Modolo, M.M., Fuster, J., Comas, J., Cosa, R., Ferrer, J., et al. (2009) Prognostic Factors and Time-Related Changes Influence Results of Colorectal Liver Metastases Surgical Treatment: A Single-Center Analysis. World Journal of Gastroenterology, 15, 2587-2594.
http://dx.doi.org/10.3748/wjg.15.2587 [23] Donadon, M., Ribero, D., Morris-Stiff, G., Abdalla, E.K. and Vauthey, J.N. (2007) New Paradigm in the Management of Liver-Only Metastases from Colorectal Cancer. Gastrointestinal Cancer Research, 1, 20-27. [24] Aloia, T.A., Vauthey, J.N., Loyer, E.M., Ribero, D., Pawlik, T.M., Wei, S.H., et al. (2006) Solitary Colorectal Liver Metastasis: Resection Determines Outcome. Archives of Surgery, 141, 460-466.
http://dx.doi.org/10.1001/archsurg.141.5.460 [25] Fernandez, F.G., Drebin, J.A., Linehan, D.C., Dehdashti, F., Siegel, B.A. and Strasberg, S.M. (2004) Five-Year Survival after Resection of Hepatic Metastases from Colorectal Cancer in Patients Screened by Positron Emission Tomography with F-18 Fluorodeoxyglucose (FDG-PET). Annals of Surgery, 240, 438-447.
http://dx.doi.org/10.1097/01.sla.0000138076.72547.b1 [26] Lee, W.S., Yun, S.H., Chun, H.K., Lee, W.Y., Kim, S.J., Choi, S.H., et al. (2008) Clinical Outcomes of Hepatic Resection and Radiofrequency Ablation in Patients with Solitary Colorectal Liver Metastasis. Journal of Clinical Gastroenterology, 42, 945-949.
http://dx.doi.org/10.1097/MCG.0b013e318064e752 [27] Lordan, J.T., Riga, A., Worthington, T.R. and Karanjia, N.D. (2009) Early and Long-Term Outcomes of Patients Undergoing Liver Resection and Diaphragm Excision for Advanced Colorectal Liver Metastases. Annals of The Royal College of Surgeons of England, 91, 483-488.
http://dx.doi.org/10.1308/rcsann.2009.91.6.483 [28] Nikfarjam, M., Shereef, S., Kimchi, E.T., Gusani, N.J., Jiang, Y.X., Avella, D.M., et al. (2009) Survival Outcomes of Patients with Colorectal Liver Metastases Following Hepatic Resection or Ablation in the Era of Effective Chemotherapy. Annals of Surgical Oncology, 16, 1860-1867.
http://dx.doi.org/10.1245/s10434-008-0225-3 [29] Choti, M.A., Sitzmann, J.V., Tiburi, M.F., Sumetchotimetha, W., Rangsin, R., Schulick, R.D., et al. (2002) Trends in Long-Term Survival Following Liver Resection for Hepatic Colorectal Metastases. Annals of Surgery, 235, 759-766.
http://dx.doi.org/10.1097/00000658-200206000-00002 [30] Chang, A.E. and Skibber, J.M. (2006) Evaluation of Tumour Markers: An Evidence-Based Guide for Determination of Clinical Utility. In: Chang, A.E., Ed., Oncology: An Evidence-Based Approach, 1st Edition, Springer, New York, 1753-1767.
http://dx.doi.org/10.1007/0-387-31056-8 [31] Gion, M., Mione, R., Barioli, P. and Dittadi, R. (1996) Dynamic Use of Tumor Marker, Rationale-Clinical Applications and Pitfalls. Anticancer Research, 16, 2279-2284. [32] Spolverato, G., Ejaz, A., Azad, N. and Pawlik, T.M. (2013) Surgery for Colorectal Liver Metastases: The Evolution of Determining Prognosis. World Journal of Gastrointestinal Oncology, 5, 207-221.
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