THE PROGNOSTIC VALUE OF CEA, BETA-HCG, AFP, CA125, CA19-9 AND C-ERB B-2, BETA-HCG IMMUNOHISTOCHEMISTRY IN ADVANCED COLORECTAL-CANCER

Background: Evaluation of the prognostic significance of a group of tumour markers and their ability to predict response to chemotherapy may allow better targeting of palliative treatment in advanced colorectal cancer. Patients and methods: Using a prospectively acquired database of 377 patients (pts) with advanced colorectal adenocarcinoma, the prognostic significance of serum CEA (342 pts), beta HCG (203 pts), AFP (208 pts), CA125 (150 pts), CA19-9 (76 pts) as well as C-erb B-2 (197 pts), beta HCG (197 pts) immunohistochemistry was investigated. Serum markers were taken prior to 5-FU based chemotherapy and immunohistochemistry was performed on diagnostic samples. Results: Tumour markers of poor prognostic significance in the univariate analysis were CEA greater than or equal to 5 mu g/l (p = 0.006; median survival (MS) 59 weeks vs. 38 weeks) and CA125 greater than or equal to 35 U/ml (p = 0.01; MS 51 weeks vs. 30 weeks). Tumour markers elevated at greater than 10 times the normal value which correlated with a poor prognosis were CEA (p=0.001; MS 47 weeks vs. 35 weeks), Serum beta HCG (p<0.0001; MS 44 weeks vs. 7 weeks) and CA125 (p < 0.0001); MS 38 weeks vs. 15 weeks). Poor performance status (>2) and poorly differentiated tumour histology were also correlated to poor survival. In the multivariate analysis, tumour markers of independent poor prognosis were CEA greater than or equal to 5 mu g/l (Hazard Ratio (HR) 1.8; 95% Confidence Internal (CI) 2.8-1.2), CEA greater than or equal to 50 mu g/l (HR 1.6; CI 2.1-1.2), CA125 greater than or equal to 35 U/ml (HR 1.5; CI 2.3-1.0), CA125 greater than or equal to 350 U/ml (HR 5.0; CI 9.6-2.6) and serum beta HCG greater than or equal to 40 IU/l (HR 11.7; CI 30-4.5). Poor performance status (HR 6.7-5.0) and poorly differentiated histology (HR 2.8-1.0) were the other important factors in the model. No pretreatment tumour marker correlated with response to chemotherapy. Conclusions: This is the largest prognostic study of each tumour marker in advanced disease and it clarifies previous conflicting reports. Serum AFP, CA19-9 and immunohistochemical stains beta HCG and C-erb B-2 have no prognostic significance. Serum CEA, beta HCG, CA125 in advanced colorectal cancer prior to chemotherapy do convey an independent poor prognosis which may reflect not just tumour burden but aggressive biology.