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Background: Results from retrospective studies show that preoperative plasma TIMP-1 and CEA levels carry independent prognostic information of patients with primary CRC. The purpose of the present, prospective study was to validate the prognostic value of preoperative plasma TIMP-1 and CEA in patients with primary CRC.
Methods: Blood samples were collected before surgery from 297 patients with stage I-IV disease. TIMP-1 and CEA levels were determined in ETDA plasma using an automated platform (ArchitectÒ, Abbott Laboratories, Chicago, USA). The Cox proportional hazards model was used with TIMP-1 and CEA on a continous scale (log base 2) adjusted for clinical covariates. The endpoints were overall survival (OS) and disease-free survival - time from operation to any event (DFS).
Results: Of the 297 patients 118 were females and 179 males with a median age of 70 (32-79) years. Using the TNM stage 50 had stage I, 91 stage II, 70 stage III and 86 stage IV distributed as 180 with colonic and 117 with rectal cancer. The median observation period was 6.1 (5.2-7.3) years and 162 deaths were recorded. In a multivariate analysis including age, gender, stage, localization, plasma TIMP-1 and CEA it was shown that plasma TIMP-1 had independent, significant prognostic value: HR = 2.9; 95% CI: 2.0-4.8; p<0.0001, whereas the value of CEA was non-significant. Restricting the analysis to stages II and III and patients not receiving adjuvant chemotherapy plasma TIMP-1 had independent, significant prognostic value: HR = 2.9; 95% CI: 1.3-6.8; p=0.013, whereas the value of CEA was non-significant. Analysis including those patients, who received adjuvant chemotherapy, showed that neither plasma TIMP-1 nor CEA had any prognostic value. This indicates that adjuvant chemotherapy may be efficient to patients with high plasma TIMP-1 levels. Similar analysis of patients with stages II and III and focus on DFS as the endpoint could not demonstrate significant results.
Conclusion: The present results achieved in a prospective study confirm that preoperative plasma TIMP-1 has independent prognostic value. In addition, the results suggest that patients with stage II or III and high plasma TIMP-1 values have particular benefit of adjuvant chemotherapy. The results must however be confirmed in prospective studies with inclusion of sufficient numbers of patients to confirm the results.