Effect of histologic type and smoking status on interpretation of serum carcinoembryonic antigen value in non-small cell lung carcinoma

Background. Serum carcinoembryonic antigen (CEA) has all of the properties desired for a biologic measure to be used as a prognostic indicator in the clinical evaluation of lung cancer. Carcinoembryonic antigen value appears to be related to tumor histologic type and patients' smoking status, which has yet to be intensively analyzed as reports available thus far have consisted of a limited number of patients. This study was undertaken to determine whether the prognostic value of CEA differs according to histologic type in a large group of patients with clinical early-stage lung cancer, and how smoking influences its value. Methods. Two series of 694 and 260 consecutive patients who underwent resection for clinical stage I lung adenocarcinoma and squamous cell carcinoma, respectively, were evaluated. We measured serum CEA before and after surgery, and analyzed its prognostic significance in relation to histologic type and its correlation with smoking status. Results. We found significantly higher CEA levels in patients with adenocarcinomas than in those with squamous cell carcinomas (7.8 versus 5.5 ng/mL; p = 0.0018), but a higher percentage of CEA-positive patients among those with squamous cell carcinoma (109 of 260, 41.9%) than those with adenocarcinoma (245 of 694, 35.3%). Clinical stage I patients with a high preoperative CEA level had a poor prognosis, and for pathologically confirmed stage I patients with a high postoperative CEA level the prognosis was worse. The prognostic value of serum CEA level was thus significantly greater for adenocarcinoma than for squamous cell carcinoma. This was probably because of a much higher proportion of smokers among patients with squamous cell carcinoma. In adenocarcinoma, the growth of which was generally less influenced by smoking, the proportion of CEA-positive smokers (49.3%, 170 of 345) was greater than that of CEA-positive nonsmokers (21.5%, 75 of 349, p < 0.0001). Additionally, in patients with adenocarcinoma, survival of nonsmokers was more greatly influenced by CEA level than that of smokers. Conclusions. Although serum CEA values measured before and after surgery are important in identifying patients at high risk of poor survival, its specificity is higher for adenocarcinoma than for squamous cell carcinoma. When serum CEA levels are checked, smoking status of patients, particularly of those with squamous cell carcinoma, should be taken into account. (C) 2004 by The Society of Thoracic Surgeons.