Clinical utility of biochemical markers in colorectal cancer: European Group on Tumour Markers (EGTM) guidelines

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Abstract

In recent years, numerous serum and cell/tissue-based markers have been described for colorectal cancer (CRC). The aim of this article was to provide guidelines for the routine clinical use of some of these markers. Lack of sensitivity and specificity preclude the use of any available serum markers such as carcinoembryonic antigen (CEA), CA 19-9, CA 242, CA 72-4, tissue polypeptide antigen (TPA) or tissue polypeptide-specific antigen (TPS) for the early detection of CRC. However, preoperative measurement of CEA is desirable as this may give independent prognostic information, help with surgical management and provide a baseline level for subsequent determinations. For patients with stage 2 (Dukes’ B) and 3 (Dukes’ C) disease who may be candidates for liver resection, CEA levels should be measured every 2-3 months for at least 3 years after diagnosis. For monitoring treatment of advanced disease, CEA should also be tested every 2-3 months. Insufficient evidence is presently available to recommend the routine use of other serum markers for monitoring purposes. Similarly, the new cell and tissue-based markers (e.g, ras, P53) cannot yet be recommended for routine clinical use.

Introduction

Biochemical markers for colorectal cancer (CRC) are potentially useful in screening for early disease, aiding diagnosis, determining prognosis, predicting likely response to specific therapies, surveillance of patients undergoing curative resection and monitoring the treatment of advanced disease. Although multiple markers have been described for CRC, confusion remains about how best to use these factors.

The European Group on Tumour Markers (EGTM) is an ad hoc group of scientists and physicians from universities, hospitals and the diagnostics industry with an interest in tumour markers [1]. The group was founded in 1997, one of its aims being the development of guidelines for the use of tumour markers. Adherence to these guidelines is of course voluntary since the ultimate decision regarding marker use must be made by the treating clinician. It is also important to note that the present guidelines are intended for routine clinical use and do not necessarily apply to clinical trials, which may have a different remit.

In 1999, the Gastrointestinal Focus Group of the EGTM published a review on the use of markers in colorectal, stomach, oesophageal, pancreatic and liver cancers [2]. The aim of this paper was to present guidelines for the clinical use of markers in CRC, focusing primarily on carcinoembryonic antigen (CEA), the most widely used marker for this malignancy.

Section snippets

Structure and function

CEA is a high molecular weight glycoprotein belonging to the immunoglobulin superfamily of molecules (for review, see Refs. 3, 4). The molecule consists of a series of Ig-like domains including a 108 amino acid variable or v region at the amino terminus, and 3 pairs of constant-2 (C-2)-like domains, each containing 178 amino acids. The carboxy-terminal contains a hydrophobic region that is modified to provide a glycosyl phosphatidylinositol link to the cell membrane.

CEA has been postulated to

Other serum markers

Although the oldest, CEA is still the best available serum marker for CRC. One of its major limitations in monitoring, however, is that 20–30% of patients with CRC fail to produce elevated serum levels, despite the presence of advanced disease. For the follow-up of these patients, other markers are therefore necessary. Markers that are of potential value for CRC patients not expressing high levels of CEA include CA 19-9, CA 242, CA 72-4, CA 50, TPA (tissue polypeptide antigen), TPS (tissue

Screening and early diagnosis

All the currently used markers for CRC have 2 main disadvantages, i.e., lack of sensitivity for early or premalignant disease and lack of specificity for malignancy. It is, however, now well established that multiple molecular alterations occur at the genome level, during the transition from normal mucosa to invasive carcinoma [53]. Genes undergoing mutation during this process might be expected to provide markers that are relatively specific for malignant or premalignant disease and also aid

Suggestions for future research

Using prospective randomised trials where possible, the following studies should be carried out:

  • Establish whether serial levels of CEA enhance patient outcome, quality of life or cost of care,

  • Investigate if elevated preoperative CEA levels can be used to select the aggressive Dukes’ B (node-negative) patients that could benefit from adjuvant chemotherapy.

  • Establish the variations in serial CEA levels that optimally define tumour progression and regression,

  • Using multivariate analysis, compare the

References (71)

  • H. Mulcahy et al.

    Urokinase-type plasminogen activator and outcome in Dukes’ B colorectal cancer

    Lancet

    (1994)
  • V. Catalano et al.

    Molecular markers predictive of response to chemotherapy in gastrointestinal tumors

    Crit. Rev. Oncol. Hematol.

    (2001)
  • European Group on Tumor Markers

    Anticancer Res.

    (1999)
  • R Klapdor et al.

    Tumor markers in gastrointestinal cancersEGTM recommendations

    Anticancer Res.

    (1999)
  • M.J. Duffy

    CEA as a marker for colorectal canceris it clinically useful

    Clin. Chem.

    (2001)
  • D.M. Parkin et al.

    Estimates of the worldwide incidence of 25 major cancers in 1999

    Int. J. Cancer

    (1999)
  • J. Lewis

    Prevention and treatment of colorectal cancerpay now or pay later

    Ann. Int. Med.

    (2000)
  • D.M.P. Thomson et al.

    The radioimmunoassay of circulating carcinoembryonic antigen of the human digestive system

    Proc. Natl. Acad. Sci. USA

    (1969)
  • R.H. Fletcher

    Carcinoembryonic antigen

    Ann. Int. Med.

    (1986)
  • Carcinoembryonic antigenits role as a marker in the management of cancer, Summary of an NIH consensus statement

    Lancet

    (1981)
  • Clinical practice guidelines for the use of tumor markers in breast and colorectal cancer

    J. Clin. Oncol.

    (1996)
  • H.L. McLeod et al.

    Tumor markers of prognosis in colorectal cancer

    Br. J. Cancer

    (1999)
  • J. Grem

    The prognostic importance of tumor markers in adenocarcinomas of the gastrointestinal tract

    Curr. Opinion Oncol.

    (1997)
  • NIH Consensus Statement, Supplemental Information for NIH Consensus Statement on Adjuvant Therapy for Patients with...
  • L.A. Carriquiry et al.

    Should carcinoembryonic antigen be used in the management of patients with colorectal cancer?

    Dis. Colon Rectum

    (1999)
  • C. Compton et al.

    American Joint Committee on Cancer Prognostic Factors Consensus ConferenceColorectal Working Group

    Cancer

    (2000)
  • C.C. Compton et al.

    Prognostic factors in colorectal cancer

    Arch. Pathol. Lab. Med.

    (2000)
  • X. Filella et al.

    CEA as a prognostic factor in colorectal cancer

    Anticancer Res.

    (1994)
  • N. Pietra et al.

    Role of follow-up in management of local recurrence of colorectal cancer, a prospective randomized study

    Dis. Colon Rectum

    (1998)
  • R.A. Graham et al.

    Post surgical surveillance of colon cancerpreliminary cost analysis of physician examination, CEA testing, chest X-ray and colonoscopy

    Ann. Surg.

    (1998)
  • J.P. Arnoud et al.

    Carcinoembryonic antigen (CEA) in diagnosis and prognosis of colorectal carcinoma

    Dis. Colon Rectum

    (1980)
  • C.G. Moertel et al.

    An evaluation of the carcinoembryonic antigen (CEA) test for monitoring patients with resected colon cancer

    JAMA

    (1993)
  • D. Hayes et al.

    Tumor marker utility grading systema framework to evaluate clinical utility of tumor markers

    J. Natl. Cancer Instit.

    (1996)
  • M. Rosen et al.

    Follow-up of colorectal cancera meta analysis

    Dis. Colon Rectum

    (1998)
  • D.J. Bruinvels et al.

    Follow-up of colorectal cancera meta-analysis

    Ann. Surg.

    (1994)
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