Clinical significance of tumor markers and an emerging perspective on colorectal cancer

Abstract

Serum carcinoembryonic antigen (CEA) and CA19-9, a carbohydrate antigen recognized by the monoclonal antibody NS19-9, are commonly used as classical tumor markers in colorectal cancer (CRC) clinics. The roles of tumor markers include: (1) diagnostic screening (diagnostic markers); (2) prediction of prognosis after treatment (prognostic markers); and (3) judgment tools for treatment effect (surveillance markers). Tumor markers can be evaluated in serum, stools, or even in tissues depending on the clinical purpose. The American Society for Clinical Oncology recommends that CEA is the only marker of choice for monitoring the response of metastatic disease to systemic therapy at present. In the present paper, we are the first to review the clinical significance of the classical tumor markers CEA and CA19-9 in serum, allowing for our original data, and present our view on the newly emerging biomarkers in CRC. Novel promising biomarkers for diagnostic, prognostic, and surveillance purposes are reviewed and considered, some of which are anticipated for further validation. For diagnostic markers, urine or serum might replace fecal samples in the near future. On the other hand, prognostic or predictive markers for treatment sensitivity may be identified from the molecular profiles of primary cancer tissues. Selection of patients who are sensitive to chemotherapy will reduce the number of patients who undergo harmful chemotherapy with no effectiveness. The optimal tumor markers would be generalized, easy to assess, and accurate, and such markers are eagerly anticipated to enable personalized tailored therapy for CRC patients.

Figure 1

Clinical outcome of colorectal cancers that had been treated at Kitasato University Hospital between 1990 and 2001. Stage was classified according to the Sixth Japanese Classification of Colorectal Cancer. Stage II patients showed excellent prognosis, as did stage 0 and I patients. On the other hand, stage III patients (stage IIIA and IIIB) showed 68% survival during the clinical course. M, mucosa; SM, submucosa; MP, muscularis proprla; SS, subserosa; SE, serosal exposure.

Figure 2

Positive rate of the preoperative serum tumor markers carcinoembryonic antigen (CEA) and CA19‐9 in colorectal carcinoma according to stage. Stage classification is based on the Japanese Classification of Colorectal Cancer.

Figure 3

Five‐year survival rate according to the preoperative serum tumor markers carcinoembryonic antigen (preCEA) or CA19‐9 (preCA19‐9) in subgroups (stage III or stage IV) of colorectal cancer between 2001 and 2004. (a) preCEA is no longer of a prognostic relevance in stage III colorectal cancer, whereas patients with elevated preCEA showed significantly poorer prognosis than those with normal preCEA.^{( 20 )} (b) In stage IV colorectal patients, cases with elevated preCA19‐9 showed significantly poorer prognosis than those with normal preCA19‐9 (P < 0.0001).

Figure 4

Interrelationship of independent prognostic factors according to logistic regression analyses. White boxes are independent prognostic factors. Gray boxes are dependent prognostic factors. These factors reflect associated independent prognostic factors. CEA, carcinoembryonic antigen; LNDE, Iymph node dissection extent; ND20, lymph node metastasis density over 20%; pN, lymph node mitastasis status; T, tumor factor.