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.


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), CA-19-9 (76 pts) as well as C-erb B-2 (197 pts). 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 > or = 5 micrograms/l (p = 0.006; median survival (MS 59 weeks vs 38 weeks) and CA125 > or = 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 > or = 5 micrograms/l (Hazard Ratio (HR) 1.8; 95% Confidence Internal (CI) 2.8-1.2), CEA > or = 50 micrograms/l (HR 1.6; CI 2.1-1.2), CA125 > or = 35 U/ml (HR 1.5; CI 2.3-1.0), CA 125 > or = 350 U/ml (HR 5.0; CI 9.6-2.6) and serum BHCG > or = 0 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.
Webb
A
A
Cancer Research Campaign Section of Medicine, Royal Marsden Hospital, Sutton, Surrey, U.K.
Scott-Mackie
P
P
Cunningham
D
D
Norman
A
A
Andreyev
J
J
O'Brien
M
M
Bensted
J
J
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism* / Q000401:mortality; D014408:Biomarkers, Tumor / Q000378:metabolism*; D018394:CA-125 Antigen / Q000378:metabolism; D018395:CA-19-9 Antigen / Q000378:metabolism; D002272:Carcinoembryonic Antigen / Q000378:metabolism; D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000401:mortality; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D011379:Prognosis; D011446:Prospective Studies; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D000509:alpha-Fetoproteins / Q000378:metabolism
D014408:Biomarkers, Tumor; D018394:CA-125 Antigen; D018395:CA-19-9 Antigen; D002272:Carcinoembryonic Antigen; D018997:Chorionic Gonadotropin, beta Subunit, Human; D018719:Erb-b2 Receptor Tyrosine Kinases; D000509:alpha-Fetoproteins