Multivariate analysis of the prognostic value of CEA and CA 19-9 serum levels in colorectal cancer

Carcinoembrionic Antigen (CEA) and carbohydrate antigen 19-9 (CA 19-9) are the most commonly used tumor-associated antigens in the management of patie nts with colorectal cancer. The aim of this study was to evaluate the progn ostic value of preoperative serum levels of CEA and/or CA 19-9 and the clas sical prognostic factors (age, sex, tumor infiltration and staging) in 495 patients. Patients and Methods. The retrospective study was performed on fr ozen sera (stored at 70 degreesC) of patients with histologically proven co lorectal cancer. Survival function estimates were calculated (Kaplan-Meier) . The patients were separated into two groups according to the preoperative marker levels. Cut-off levels calculated at a specificity of 100% versus h ealthy individuals were used: < 4 ng/mL versus <greater than or equal to> 4 ng/mL for CEA and < 60 U/mL versus <greater than or equal to> 60 U/mL for CA 19-9 Survival curve differences were assessed using the log-rank-test. M ulivariate Cox's proportional hazard regression analysis was performed to e xamine the association between tumor marker levels and survival time. Class ical prognostic factors such as age, sex, tumor infiltration, tumor stage ( Dukes' classification) were included as covariants. The mantel-Haenszel met hod was used to assess the survival rate of patients with colorectal carcin oma and high versus low levels of tumor-associated antigens according to tu mor stages. Results. The Dukes' stages (log-rank chi-square = 231.9; p < 0. 0001) represent the best prognostic factor besides the preoperative values of CA 19-9 (log-rank chi-square = 162.5). CEA shows a log-rank chi-square o f 71.4 Thus, CEA and CA 19-9 can be used to discriminate two groups of pati ents with significantly different survival times (p < 0.0001). The importan ce of different parameters in providing additional prognostic information w as evaluated by multivariate analysis. Only items of statistically signific ant prognostic relevance (univariate analysis) were used for this analysis. Estimated relative risk of death adjusted for tumor stage were 5.5 conside ring Dukes' stage A versus Dukes' stage B/C and Dukes' stage B/C versus Duk es' stage D, respectively, and an increasing relative risk of 27.5 for Duke s' stage A versus Dukes' stage D (p < 0.001). The relative risk for preoper ative CA 19-9 serum concentrations (<greater than or equal to> 60 U/mL vers us < 60 U/mL) was 2.3 (p < 0.001) and for preoperative CEA concentrations ( greater than or equal to 4 ng/mL versus < 4 ng/mL) 1.4 (p < 0.07). For CEA the 2-year survival rates in the group of patients with preoperative serum concentrations > 4 ng/mL versus < 4 ng/mL and Dukes' stage D were 16% versu s 38%, in Dukes' stage B/C 73% versus 91% and in Dukes' stage A 100% versus 98%. For CA 19-9 the 2-year survival rates in the group of patients with p reoperative serum concentrations <greater than or equal to> 60 U/mL versus < 60 U/mL and Dukes' stage D were 10% versus 39%, whilst in Dukes' stage B/ C 58% versus 87%. In the group of patients with Dukes' stage A with serum l evels <greater than or equal to> 60 U/mL a 2-years survival rate of 100% wa s found. Conclusion: The postoperative Dukes' classification represents the best prognostic information besides the preoperative values of CA 19-9. Th e predictive information provided by preoperative CA 19-9 serum levels is i ndependent from that obtained by the other factors investigated. Only Dukes ' classification and CA 19-9 levels showed statistical significance (p < 0. 001).