Tumor Biology

, Volume 36, Issue 3, pp 1519–1527 | Cite as

The prognostic role of baseline CEA and CA 19-9 values and their time-dependent variations in advanced colorectal cancer patients submitted to first-line therapy

  • M. Tampellini
  • A. Ottone
  • I. Alabiso
  • C. Baratelli
  • L. Forti
  • A. Berruti
  • E. Aroasio
  • G. V. Scagliotti
Research Article


Serum marker evaluation is an easily available prognostic indicator that may help clinicians to discriminate patients with an aggressive disease; there are few and small-sized studies exploring the prognostic role of baseline carcinoembryonic antigen (CEA) values and their variations during first-line therapy, and even fewer data are available for carbohydrate antigen 19–9 (CA 19-9). Our aim was to analyze the role of those prognostic markers to exploit them in daily clinical practice. Data of 892 patients with marker determination before and 3 and/or 6 months during therapy were extracted from two institutional databases. Patients were grouped according to single marker variation as always negative (G0), decreasing (G1), stable (G2), or increasing (G3). We evaluated the progression-free survival (PFS) and the overall survival (OS) of all the patents and correlated them with CEA and CA 19-9 values. A concordance between response to therapy and marker decrease was evident in 50.2 % and in 34.4 % of the patients for CEA and CA 19-9. Patients with low CEA or CA 19-9 baseline values had a longer PFS (15.1 vs. 10.5; 13.6 vs. 10.2 months) and OS (32.0 vs. 22.3; 30.5 vs. 20.1 months). The same results of PFS and OS were obtained by analyzing the data of the four different groups. Multivariate analyses confirmed the independent prognostic role of CEA and CA 19-9. Baseline CEA and CA 19-9 levels and their kinetics demonstrated to be independent prognostic factors. CA 19-9 dosage is not recommended; a possible role of CA 19-9 in patients with negative CEA could be worth further evaluation.


CEA Ca 19-9 Colorectal cancer Biological markers 


  1. 1.
    Jemal A, Bray F, Center MM, et al. Global cancer statistics. CA Cancer J Clin. 2011;61(2):69.CrossRefPubMedGoogle Scholar
  2. 2.
    Goldstein MJ, Mitchell EP. Carcinoembryonic antigen in the staging and follow-up of patients with colorectal cancer. Cancer Investig. 2005;23(4):338–51.CrossRefGoogle Scholar
  3. 3.
    Al-Sarraf M, Baker L, Talley RW, et al. The value of serial carcinoembryonic antigen (CEA) in predicting response rate and survival of patients with gastrointestinal cancer treated with chemotherapy. Cancer. 1979;44(4):1222–55.CrossRefPubMedGoogle Scholar
  4. 4.
    De Gramont A, Krulic M, Kadi J, et al. High-dose folinic acid and 5-fluorouracil bolus and continuous infusion in advanced colorectal cancer. Eur J Cancer Clin Oncol. 1988;24(9):1499–503.CrossRefPubMedGoogle Scholar
  5. 5.
    Barone C, Astone A, Cassano A, et al. Advanced colon cancer: staging and prognosis by CEA test. Oncology. 1990;47(2):128–32.CrossRefPubMedGoogle Scholar
  6. 6.
    Michl M, Koch J, Laubender RP, et al. Tumor markers CEA and CA 19-9 correlate with radiological imaging in metastatic colorectal cancer patients receiving first-line chemotherapy. Tumour Biol. 2014 Jul 15.Google Scholar
  7. 7.
    Galli C, Basso D, Plebani M. CA 19-9: handle with care. Clin Chem Lab Med. 2013;51(7):1369–83.CrossRefPubMedGoogle Scholar
  8. 8.
    Hayward JL, Carbone PP, Heuson JC, et al. Assessment of response to therapy in advanced breast cancer: a project of the programme on clinical oncology of the international union against cancer, Geneva, Switzerland. Cancer. 1977;39:1289–94.CrossRefPubMedGoogle Scholar
  9. 9.
    Therasse P, Arbuck SG, Eisenhauer EA, et al. New guidelines to evaluate the response to treatment in solid tumors. J Natl Cancer Inst. 2000;92:205–16.CrossRefGoogle Scholar
  10. 10.
    Boeck S, Haas M, Laubender RP, et al. Application of a time-varying covariate model to the analysis of CA 19-9 as serum biomarker in patients with advanced pancreatic cancer. Clin Cancer Res. 2010;16(3):986–94.CrossRefPubMedGoogle Scholar
  11. 11.
    Custodio A, Feliu J. Prognostic and predictive biomarkers for epidermal growth factor receptor-targeted therapy in colorectal cancer: beyond KRAS mutations. Crit Rev Oncol Hematol. 2013;85(1):45–81.CrossRefPubMedGoogle Scholar
  12. 12.
    Liao X, Morikawa T, Lochhead P, et al. Prognostic role of PIK3CA mutation in colorectal cancer: cohort study and literature review. Clin Cancer Res. 2012;18(8):2257–68.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Lochhead P, Imamura Y, Morikawa T, et al. Insulin-like growth factor 2 messenger RNA binding protein 3 (IGF2BP3) is a marker of unfavourable prognosis in colorectal cancer. Eur J Cancer. 2012;48(18):3405–13.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Stillwell AP, Ho YH, Veitch C. Systematic review of prognostic factors related to overall survival in patients with stage IV colorectal cancer and unresectable metastases. World J Surg. 2011;35:684–92.CrossRefPubMedGoogle Scholar
  15. 15.
    Mitsuyama Y, Shiba H, Haruki K, et al. Carcinoembryonic antigen and carbohydrate antigen 19-9 are prognostic predictors of colorectal cancer with unresectable liver metastasis. Oncol Lett. 2012;3(4):767–71.PubMedPubMedCentralGoogle Scholar
  16. 16.
    Altman DG, Lausen B, Sauerbrei W, et al. Dangers of using “optimal” cutpoints in the evaluation of prognostic factors. J Natl Cancer Inst. 1994;86:829–35.CrossRefPubMedGoogle Scholar
  17. 17.
    Strimpakos AS, Cunningham D, Mikropoulos C, Petkar I, Barbachano J, Chau I. The impact of carcinoembryonic antigen flare in patients with advanced colorectal cancer receiving first-line chemotherapy. Ann Oncol. 2010;21:1013–9.CrossRefPubMedGoogle Scholar
  18. 18.
    Boeck S, Stieber P, Holdenrieder S, et al. Prognostic and therapeutic significance of carbohydrate antigen 19-9 as tumor marker in patients with pancreatic cancer. Oncology. 2006;70:255–64.CrossRefPubMedGoogle Scholar
  19. 19.
    Charbel H, Al-Kawas FH. Cholangiocarcinoma: epidemiology, risk factors, pathogenesis, and diagnosis. Curr Gastroenterol Rep. 2011;13(2):182–7.CrossRefPubMedGoogle Scholar
  20. 20.
    Jamaludin AZ, Metassan MM, Zainal-Abidin Z, et al. Elevated serum CA 19-9 in association with Hashimoto thyroiditis. Singap Med J. 2010;51(8):143–5.Google Scholar
  21. 21.
    Bertino G, Ardiri AM, Calvagno GS, et al. In chronic viral hepatitis without malignancy, abnormal serum carbohydrate 19-9 antigen levels are associated with liver disease severity and are related to different viral aetiology. Dig Liver Dis. 2010;42:457–9.CrossRefGoogle Scholar
  22. 22.
    Tampellini M, Berruti A, Bitossi R, et al. Prognostic significance of changes in CA 15-3 serum levels during chemotherapy in metastatic breast cancer patients. Breast Cancer Res Treat. 2006;98(3):241–8.CrossRefPubMedGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • M. Tampellini
    • 1
  • A. Ottone
    • 1
  • I. Alabiso
    • 2
  • C. Baratelli
    • 1
  • L. Forti
    • 3
  • A. Berruti
    • 4
  • E. Aroasio
    • 1
  • G. V. Scagliotti
    • 1
  1. 1.SCDU OncologiaAOU San Luigi GonzagaOrbassanoItaly
  2. 2.SC OncologiaOspedale San Giovanni BoscoTorinoItaly
  3. 3.SCDU OncologiaAOU Maggiore della CaritàNovaraItaly
  4. 4.Dipartimento di Specialità Medico-Chirurgiche, Scienze Radiologiche e Sanità PubblicaUniversità di Brescia, Oncologia Medica. Azienda Ospedaliera Spedali CiviliBresciaItaly

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