High Carcinoembryonic Antigen Levels Research Articles

Relapsed prostate cancer with neuroendocrine differentiation and high serum levels of carcinoembryonic antigen without elevation of prostrate‐specific antigen: A case report

A 62-year-old man had been treated with combined androgen blockade due to cT2bN1M0 prostate cancer, and his serum prostate-specific antigen (PSA) levels decreased and remained under the level of 0.5 ng/mL during therapy. Approximately 40 months after the initial therapy, difficulty on urination and constipation developed gradually, and serum carcinoembryonic antigen (CEA) and pro-gastrin-releasing peptide (ProGRP) levels were high at this point. He underwent transrectal and transurethral biopsy of the prostate, which revealed adenocarcinoma positive for CEA and chromogranin A. He received palliative pelvic irradiation, and oral estramustine phosphate and etoposide combined therapy. Tumor markers decreased and clinical symptoms improved for several months. The patient died of encephalopathy of unknown etiology approximately 11 months after the relapse.

Multivariate Analysis of Prognostic Determinants for Colorectal Cancer Patients with High Preoperative Serum CEA Levels: Prognostic Value of Postoperative Serum CEA Levels

High preoperative serum carcinoembryonic antigen (CEA) levels have been well investigated and found to be associated with poor prognosis in patients with colorectal cancer (CRC). However, it has been observed that the outcome varies after curative resection, along with postoperative serum CEA levels; some patients continue to have high postoperative serum CEA levels while postoperative CEA levels return to normal in others. The purpose of this study was to determine the prognostic significance of postoperative serum CEA levels in CRC patients with high preoperative serum CEA levels. Between January 2002 and December 2004, 423 CRC patients underwent operation in our hospital; 181 (42.8%) had high preoperative serum CEA levels and were enrolled in this study. Among the 181 patients, 165 patients had curative resection; the remaining 16 had stage IV disease, so they underwent palliative surgery and were subsequently excluded from analysis. Pre- and postoperative serum CEA levels were measured and analyzed. All patients had curative resection and were divided into two groups according to postoperative serum CEA levels: one group comprised patients with postoperative serum CEA > or = 5 ng/mL (n = 80) and the other group comprised patients with postoperative serum CEA levels < 5 ng/mL (n = 85). Postoperative serum CEA levels were significantly related to location of primary tumors (p = 0.042), lymph node metastases (p = 0.009), TNM stage (p = 0.001), and postoperative relapse (p = 0.004). The results of multivariate analysis showed that both lymph node metastases and high postoperative serum CEA levels (> or = 5 ng/mL) were independent prognostic factors for CRC patients after curative resection. Postoperative serum CEA levels can be a single independent prognostic determinant in CRC patients with high preoperative serum CEA levels. Intensive follow-up and adjuvant therapy may be necessary in CRC patients who continue to have high postoperative serum CEA levels even after curative resection.

Lung cancer patients with postoperative normalization of serum carcinoembryonic antigen level: Predictive factors for re‐elevation

AbstractBackground: Postoperative normalization of serum carcinoembryonic antigen (CEA) level has been reported to be a favorable prognostic predictor in lung cancer. However, serum CEA levels of some patients’ groups re‐elevate during their postoperative course. The aim of study was to find predictors of CEA re‐elevation in patients with preoperative high and postoperative normal CEA.Methods: Sixty‐one consecutive lung cancer patients with preoperative high serum CEA level (&gt;5 ng/mL) and postoperative normal level were reviewed retrospectively. Among these patients, serum CEA levels of 23 patients re‐elevated during their postoperative course. We compared patients with and without re‐elevation of serum CEA levels.Results: The 5‐year survival of patients with and without re‐elevation of serum CEA level was 13.20% and 88.68%, respectively (P &lt; 0.0001). There are significant differences in pN2 status and CEA level in pleural lavage fluid between patients with and without re‐elevation of serum CEA level.Conclusions: Our results showed that pN2 status and lavage CEA level were related to the re‐elevation of serum CEA level.

Tissue inhibitor of metalloproteinases-1 in the postoperative monitoring of colorectal cancer

The aim of this study was to investigate whether the pre- and postoperative plasma levels of tissue inhibitor of metalloproteinases-1 (TIMP-1) were associated with outcome in colorectal cancer (CRC). Pre- and postoperative plasma TIMP-1 from 280 curatively resected CRC patients and carcinoembryonic antigen (CEA) in corresponding serum samples were measured and correlated with patient outcome (death, local recurrence (LR) and distant metastases (DM)). The results showed that the course of plasma TIMP-1 from pre- to postoperative levels correlated with patient outcome ( P = 0.005). However, postoperative plasma TIMP-1 alone was strongly associated with patient outcome, high TIMP-1 predicting short survival ( P = 0.002). Combining postoperative TIMP-1 and CEA demonstrated that high TIMP-1 and CEA levels predicted poor outcome ( P < 0.0001); multivariate analysis identifying both parameters as strong prognostic factors for survival, LR and DM ( P < 0.0001). In conclusion, postoperative plasma TIMP-1 predicts patient outcome both alone and in combination with CEA. Postoperative TIMP-1 may be a marker of residual disease after primary surgery for CRC.

Diagnostic strategy based on preoperative serum CEA levels in clinical stage IA NSCLC

17011 Background: Following surgery, clinical stage IA NSCLC diagnosed using non-interventional examinations is occasionally pathological stage III or IV. The level of carcinoembryonic antigen (CEA) in serum has been reported to be a predictor of up-staging to advanced stages, however, there are few multi-center studies of serum CEA that utilized a short accrual period. Methods: A multi-center retrospective study was performed to assess serum CEA level as a predictor of advanced stage in 862 consecutive patients with clinical stage IA NSCLC from 2002 to 2004. The subjects were 493 males with a mean age of 65.2 years old, 460 of whom were smokers, who had a total of 689 adenocarcinomas with a mean tumor size of 19.5 cm. They were divided into 4 groups by smoking status and adenocarcinoma histology, after which AUC was calculated using an ROC curve, which provided an estimate of the probability efficiency of pathological diagnosis of stage III or stage IV. When AUC was greater than 0.7, sensitivity, specificity, and positive predictive values were calculated, and multivariate Cox regression analysis was performed to confirm independence. Results: There were 72 cases (8.1%) in an advanced stage. AUC was greater than 0.7 in the group of non-smokers with an adenocarcinoma (n = 413), in which the sensitivity, specificity, and positive predictive values were 0.14, 0.97, and 0.64, respectively, with a CEA cut-off level of 20 ng/ml. Thus, serum CEA level was shown to be an independent predictive factor. Conclusions: In smokers with an adenocarcinoma, a high level of CEA in serum was frequently found in those with pathologically advanced disease, thus intervention should be mandated in such cases. [Table: see text] No significant financial relationships to disclose.

Prognostic significance of CEA levels and positive cytology in peritoneal washings in patients with colorectal cancer

The aims of this prospective study were to determine carcinoembryonic antigen (CEA) levels and incidence of cytology in peritoneal washings of patients with colorectal cancer, correlate the results with various histopathological factors and determine their significance as prognostic factors of the disease. From 1992 to 1999, 98 patients with adenocarcinoma of the colon or intraperitoneal rectum underwent curative surgery and enrolled in this study. Overall, 25 (26.3%) of 95 patients were found to have positive cytology. The proportion of patients with positive cytology was higher in the recurrence group (36.4%) than in the groups of 5-year survival and hepatic metastases (24.6% and 26.3%, respectively), but this difference was not significant. The 5-year survival group had the lowest peritoneal CEA levels compared with the other groups, but this difference was not significant. Peritoneal cytology and CEA level alone were not sensitive, specific or accurate enough indicators in predicting survival, hepatic metastases or local recurrence. The analysis of patients with positive cytology and high peritoneal CEA level revealed that their combination can predict local recurrence with accuracy of 85%. The presence of free malignant cells, as detected by cytology and CEA level, in the peritoneal cavity of patients with resectable colorectal cancer had no detectable impact on survival, hepatic metastases or local recurrence rate. However, local recurrence can be predicted with accuracy of 85% in patients who have positive cytology and high peritoneal CEA level at the same time.

Value of carcinoembryonic antigen and cytokeratins for the detection of recurrent disease following curative resection of colorectal cancer

To evaluate the efficacy of postoperative serial assay of carcinoembryonic antigen (CEA) and cytokeratins for the detection of recurrent disease in patients with colorectal adenocarcinoma after radical surgery. Between 1993 and 2000, 120 patients with colorectal adenocarcinoma underwent radical surgery in the Department of Surgical Gastroenterology, Federal University of Sao Paulo-Escola Paulista de Medicina, Sao Paulo, Brazil. Periodic postoperative evaluation was performed by assaying markers in peripheral serum, colonoscopy and imaging examination. Presence of CEA was detected using the Delfia method with 5 microg/L threshold, and cytokeratins using the LIA-mat TPA-M Prolifigen method with 72 U/L threshold. In the first postoperative year, patients without recurrent disease had normal levels of CEA (1.5 +/- 0.9 microg/L) and monoclonal tissue polypeptide antigen-M (TPA-M, 64.4 +/- 47.8 U/L), while patients with recurrences had high levels of CEA (6.9 +/- 9.8 microg/L, P < 0.01) and TPA-M (192.2 +/- 328.8 U/L, P < 0.05). During the second postoperative year, patients without tumor recurrence had normal levels of CEA (2.0 +/- 1.8 microg/L) and TPA-M (50.8 +/- 38.4 U/L), while patients with recurrence had high levels of CEA (66.3 +/- 130.8 microg/L, P < 0.01) and TPA-M (442.7 +/- 652.8 U/L, P < 0.05). The mean follow-up time was 22.3 mo. There was recurrence in 23 cases. Five reoperations were performed without achieving radical excision. Rises in tumor marker levels preceded identification of recurrences: CEA in seven (30%) and TPA-M in eleven individuals (48%). Intensive follow-up by serial assay of CEA and cytokeratins allows early detection of colorectal neoplasm recurrence.

血清中癌胎児性抗原が高値を示した上顎洞腺扁平上皮癌の１例

Adenosquamous carcinoma is an uncommon malignant tumor, and histopathologically shows components of adenocarcinoma and squamous cell carcinoma. We report a case of adenosquamous carcinoma in the maxillary sinus associated with an abnormally high level of serum carcinoembryonic antigen (CEA). A 78-yearsold man visited our clinic because of swelling of the left side of the buccal and palatal regions. At presentation, there was a diffuse extraoral swelling extending from the ala of the nose to the infraorbital region, and intraoral swelling and induration in the gingivo-buccal sulcus. A computed tomographic (CT) scan revealed a solid mass in the maxillary sinus, with destruction of the front wall of the maxillary sinus. The serum CEA level was abnormally elevated (50.4ng/ml); however, no distant metastasis was detected. Biopsy was performed under the clinical diagnosis of a malignant tumor of the maxilla. Histopathological examination suggested an adenosquamous carcinoma. Suprahyoid neck dissection (Left-side), ligation of external carotid artery, and subtotal maxillectomy were performed with the patient under general anesthesia. The final histopathological diagnosis was adenosquamous carcinoma. One month after the operation, CEA gradually decreased to 8.9ng/ml. One year after the operation, CEA level was 7.6ng/ml, with no apparent evidence of recurrence.

Titration of serum p53 antibodies in patients with gastric cancer: a single-institute study of 40 patients

Alterations of the p53 tumor suppressor gene are the most commonly observed genetic abnormalities in many different types of human malignancies. The accumulation of mutant p53 often leads to the production of p53 antibody (p53-Ab) in the sera of patients with various cancers. To evaluate the clinical implications of serum p53-Abs in patients with gastric cancer, we compared p53-Abs with conventional tumor markers such as carcinoembryonic antigen (CEA) and carbohydrate antigen (CA)19-9. Serum samples were obtained preoperatively from 40 patients with histologically confirmed gastric adenocarcinoma, including 28 (70%) patients in stage Ia. The serum p53-Abs were assessed by enzyme-linked immunosorbent assay, using a new version of a highly specific, quantitative p53-Abs Kit (MESACUP Kit II). p53-Abs were detected in 6 (15%) of 40 patients with gastric cancer, including 3 patients with early gastric cancer. Seven (17.5%) of the 40 patients were positive for CEA in serum. However, none of 7 patients with high CEA levels were positive for p53-Abs. No significant correlation of p53-Abs with patient age, sex, pathological parameters, tumor markers such as CEA and CA19-9, or poor survival (P = 0.116) was observed. Although we employed the latest version of the p53-Abs Kit, the sensitivity of serum p53-Ab in gastric cancer patients was relatively low. No correlation was found between the presence of p53-Ab and the staging of cancer or survival. However, serum p53-Ab was detectable in patients with gastric cancer even in the early stages of disease. In addition, it may be independent of CEA and CA19-9.

Relationship between genetic alterations and prognosis in sporadic colorectal cancer

Because chromosomal chromosomal instability (CIN) and microsatellite instability (MSI) are important genetic alterations in colorectal cancers, we classified the sporadic colorectal cancers (CRC) on the status of the CIN and MSI and explored their molecular profiles. A total of 213 colorectal tumors were collected for analysis of DNA ploidy, MSI, loss of heterozygosity (LOH), mutation of p53 (exons 5 to 9), Ki-ras (exons 1 and 2) and BRAF (V599E). Relationships between clinicopathological variables and molecular analyses were analyzed with the chi(2) test (Yates' correction). Kaplan-Meier survival curves were compared using log-rank test. Variables with p < 0.1 were entered into the Cox regression hazard model for multivariate analysis. High microsatellite instability (MSI-H) existed in 19 tumors (8.9%), which were more likely to be right-sided (31.6%) with poor differentiation (26.3%). Seventy-one (33.3%) tumors were diploid and 142 (66.7%) were aneuploid. Mutations in p53, Ki-ras and BRAF were found in 45.1%, 41.8% and 4.2% of tumors, respectively. Based on MSI, and CIN, 3 classes were defined: (i) High microsatellite instability MSI-H tumors: young age, high carcinoembryonic antigen (CEA) level, right colon, poorly differentiated, mucin production, high BRAF mutation, lower allelic loss and relatively good prognosis; (ii) Microsatellite stability (MSS) diploid tumors: right colon, poorly differentiated, less infiltrative tumor, mucin production, lower allelic loss and low p53, BRAF mutation; (iii) MSS aneuploid tumors: more infiltrative invasion, greater allelic loss and high p53 mutation. According to multivariate analysis, tumor stage and p53 mutation were significantly associated with disease progression. The MSS diploid and MSS aneuploid CRCs could be subtyped with p53 mutation and had different prognostic outcome and molecular profiles. The 4-year disease-free survival (DFS) of patients with MSS-diploid, wild-type p53 tumors was 67% and significantly higher than those of patients with MSS-diploid, mutant p53 CRC (30%, p = 0.003). The same trend was found in patients with MSS-aneuploid CRC(wild p53 vs. mutant p53, 64% vs. 41%, p = 0.009). We concluded that CIN, MSI and p53 mutation status might be used as a multiple parameter profile for the prognosis of sporadic colorectal cancer.

Prognostic Determinants for Lung Cancer Patients with Preoperative High Serum Carcinoembryonic Antigen Levels

Several reports have indicated that preoperative high serum carcinoembryonic antigen (CEA) levels are associated with poor survival after surgical resection in lung cancer. 82 consecutive lung cancer patients with preoperative high serum CEA levels (> 5 ng/mL) were included in this study. Postoperative serum CEA level was also measured. Prognostic indicators were evaluated. Among patients with a preoperative high serum CEA level, a serum CEA level higher than 10 ng/mL, pT status, pN status, and positive pleural lavage cytology findings were unfavorable prognostic indicators, whereas age, gender, smoking status, histologic subtype were not. Postoperative serum CEA levels of all but 2 patients decreased, however those of 28 patients did not return to normal range. Our result showed that patients with postoperative high serum CEA level had poor prognosis. Multivariate analysis demonstrated that pT status, pN status, and postoperative high serum CEA level was an independent prognostic determinant. In lung cancer patients with preoperative high serum CEA levels, pT status, pN status, and normalization of serum CEA level after surgery are significant prognostic determinants.

Disseminated Medullary Thyroid Carcinoma Despite Early Thyroid Surgery in the Multiple Endocrine Neoplasia-2A Syndrome

A 51/2-year-old boy, with a family history of multiple endocrine neoplasia (MEN)-2A syndrome, was evaluated for presence of MEN-2A and medullary thyroid carcinoma (MTC). DNA diagnostics confirmed MEN-2A. Basal (360 ng/L) and pentagastrin stimulated (430 ng/L) calcitonin (CT) levels were slightly elevated, plasma carcinoembryonic antigen (CEA) was normal. Within a year both tumor markers increased and total thyroidectomy was performed. Histologic examination did not show MTC. In the following years, both tumor markers increased progressively but despite the use of multiple imaging techniques no metastases were localized. After 6 years, biopsy of a palpable lymph node showed MTC. The boy was treated with total cervical, suprahyoidal, and mediastinal lymph node dissection, showing MTC in almost all nodes. Again, the tumor markers remained high. At this point in time, the disadvantages of further medical interventions were outweighed against the chance for cure and it was decided to shift the goal of treatment toward palliation rather than cure. At the last visit the boy was clinically well with persistent extremely high levels of plasma CEA and CT. In conclusion, when prophylactic thyroidectomy in the MEN-2A syndrome has failed, it may be best to withdraw from further interventions to prevent more damage.

Cytokeratins and carcinoembryonic antigen in diagnosis, staging and prognosis of colorectal adenocarcinoma

To evaluate the serum levels of cytokeratins and carcinoembryonic antigen (CEA) in diagnosis, staging and prognosis of patients with colorectal adenocarcinoma. The sample consisted of 169 patients. One hundred blood donors formed the control group. Radical surgery was performed on 120 patients, with an average follow-up duration of 22.3 mo. Relapses occurred in 23 individuals after an average of 18.09 mo. CEA was assayed via the Delfia method with a limit of 5 ng/mL. Cytokeratins were assayed via the LIA-mat TPA-M Prolifigen method with a limit of 72 U/L. In the diagnosis of patients with colorectal adenocarcinoma, CEA showed a sensitivity of 56%, a specificity of 95%, a positive predictive value of 94%, a negative predictive value of 50% and an accuracy of 76.8%. TPA-M had a sensitivity of 70%, a specificity of 96%, a positive predictive value of 97%, a negative predictive value of 66% and an accuracy of 93.6%. The elevation of one of the markers was shown to have a sensitivity of 76.9%, a specificity of 91%, a positive predictive value of 93.5%, a negative predictive value of 70% and an accuracy of 83.6%. There was no variation in the levels of the markers according to the degree of cell differentiation while there was an elevation in their concentrations in accordance with the increase in neoplastic dissemination. There was a statistically significant difference between the patients with stage IV lesions and those with stages I, II and III tumors. With regard to CEA, the average level was 14.2 ng/mL in patients with stage I lesions, 8.5 ng/mL in patients with stage II lesions, 8.0 ng/mL in patients with stage III lesions and 87.7 ng/mL in patients with stage IV lesions. In relation to TPA-M, the levels were 153.1 U/L in patients with stage I tumors, 106.5 U/L in patients with stage II tumors, 136.3 U/L in patients with stage III tumors and 464.3 U/L in patients with stage IV tumors. There was a statistical difference in patients with a high CEA level in relation to a shorter survival (P<0.05). However, there was no correlation between patients with high TPA-M levels and prognostic indices of patients undergoing radical surgery. Cytokeratins demonstrate a greater sensitivity than CEA in the diagnosis of colorectal adenocarcinoma. There is an increase in the sensitivity of the markers with tumor dissemination. Cytokeratins cannot identify the worse prognosis in patients undergoing radical surgery. Cytokeratins constitute an advance in the direction of a perfect tumor marker in the treatment of patients with colorectal cancer.

Tumour CEA as predictor of better outcome in squamous cell carcinoma of the lung

High levels of serum carcinoembryonic antigen (S-CEA) are considered a negative prognostic factor in non-small-cell lung cancer (NSCLC), while the prognostic value of tumour CEA (T-CEA) is unknown. We investigated the prognostic role of T-CEA in radically resected early stage NSCLC. We measured preoperative S-CEA levels and T-CEA in 146 patients with stage 1-2 NSCLC, and analysed their influence on survival. In patients positive for T-CEA, 3-year survival was 80%, compared to 65% in T-CEA-negative patients (p=0.03). After stratification by histology, T-CEA positivity was prognostic of better survival in squamous cell carcinoma (SCC) (p=0.024) but not in adenocarcinomas (ADK) (p=0.87). Multiple Cox regression analysis showed that T-CEA positivity was an independent predictor of better survival in patients with early stage NSCLC (p=0.02). In SCC patients, the magnitude of the hazard ratio was confirmed even if the precision of the estimate is decreased (p=0.06). In conclusion, T-CEA expression appears to be an important prognostic factor in early stage SSC of the lung.

Epidermoid cyst of the spleen with elevated levels of CA125 and carcino-embryonic antigen

Epidermoid splenic cyst is characterised by a single layer of epithelium. Although specific findings can be depicted with ultrasonography (USG) and CT, elevated levels of carcino-embryonic antigen (CEA), CA19–9 or CA125 in serum and cyst fluids have recently been used in the diagnosis [1,2]. A 12-year-old female patient was admitted with swelling and pain on the left side of abdomen. Abdominal USG and CT revealed that the spleen was enlarged and contained two cysts. The larger cyst was very close to the hilum (Fig. 1). Serum analysis revealed high levels of CA125 (35 ng/ml) and CEA (150 U/ml). She underwent total splenectomy because the tributaries of splenic artery and vein overlaying the hilar cyst prevented an alternative operative procedure. Examination of cyst fluid also revealed high levels of CA125 (70 ng/ ml) and CEA (1500 U/ml). Both cysts were thin-walled and lined with a single layer of squamous epithelium in histologic examination. CA125 and CEA returned to normal levels within 3 months. Epidermoid cysts are lined by stratified squamous epithelium. It is thought that they develope after invagination of the capsular surface mesothelium with subsequent squamous metaplasia [3]. Mostly they give signs and symptoms in late childhood and may regress completely. Cysts larger than 5 cm require resection because of their progressive growth and in order to prevent the potential severe complications such as rupture and haemorrhage [3]. Higaki et al. [1] reported that serum CEA, CA19–9 and CA125 levels had been elevated in patients with epidermoid cyst in whom epithelium was positive for anti-CEA and anti-CA19–9 antibodies. This finding shows that these markers are products of the squamous epithelium and leak into the bloodstream, presumably as a result of trauma or increasing pressure within the cyst.

First and Repeat Resection of Colorectal Liver Metastases in Elderly Patients

The objective of this study was to evaluate the short- and long-term outcome after first and repeat resection in patients older than 70 years. Liver resection is the best treatment for colorectal liver metastases and is currently increasingly performed in elderly patients. The benefit of resection for these patients needs to be evaluated. Between 1990 and 2000, 56 first and 16 repeat liver resections were performed in 61 patients older than 70 years. Patients were identified from a prospective database and records were reviewed retrospectively. First and repeat liver resection resulted, respectively, in a 0% and 7% postoperative mortality rate and a 41% and 38% complication rate, respectively. Median survival after first resection of 53 patients with R0 resection was 33 months, and the 5-year survival rate was 22%. Factors associated with poor long-term survival in multivariate analysis were extrahepatic disease, high carcinoembryonic antigen level over 200 ng/mL, and the presence of 3 or more liver metastases. Patients without these risk factors showed a median survival of 42 months and a 5-year survival rate of 36%. Repeat liver resection resulted in a median survival of 17 months and in a 3-year survival rate of 25%. First and repeat liver resection for colorectal liver metastases can be performed safely in patients older than 70 years. A 5-year survival rate similar to those of younger patients can be expected after first liver resection for patients without the presence of risk factors.

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.

Invited commentary

Since the early 1970s, several studies have shown that high carcinoembryonic antigen (CEA) levels were a potential marker of poor prognosis in nonsmall cell lung cancer (NSCLC). Abnormally elevated CEA levels were reported in 30% to 70% of patients with NSCLC and were most frequently observed in patients with adenocarcinoma and advanced stage carcinoma. Despite its potential value, CEA was often falsely elevated in smokers and in patients with restrictive or obstructive pulmonary disease. Consequently, the stage of disease and performance status of the patients remained better predictors of survival than CEA, and in 1997, The American Thoracic Society and the European Respiratory Society did not recommend the routine measurement of CEA for patients with NSCLC, because it did not influence the management of these patients. However, the past decade has been associated with significant changes in the mode of presentation and treatment of NSCLCs. Adenocarcinoma has become more frequent than squamous cell carcinoma in North America and Asia, low-dose chest computed tomography has been popularized, the incidence of bronchioloalveolar carcinoma has been rising (particularly in nonsmokers), and chemotherapy has been proven beneficial in patients with early stage NSCLC. These changes have brought a whole new set of questions in our current management of patients with stage IA and IB NSCLC. Do all patients with very early stage NSCLC require a lobectomy or would segmentectomy be an appropriate operation in some patients? Do all bronchioloalveolar carcinomas have to be treated similarly to other NSCLCs, or is there a spectrum of disease between bronchioloalveolar carcinoma and adenocarcinoma? Do all patients with early stage NSCLC require chemotherapy in addition to surgery, and should they receive it before or after surgery? Refinements to our current evaluation of patients with early stage NSCLC is needed to answer some of these questions. The measurement of tumor markers could potentially be part of this evaluation. Carcinoembryonic antigen is an inexpensive and readily available serum marker that has been shown to be one of the few independent preoperative predictors of survival in patients with small adenocarcinoma. High preoperative CEA level has also been shown to be associated with a higher risk of nodal metastasis in patients with NSCLC, and particularly in patients with clinical stage IA adenocarcinoma. The combination of a normal preoperative CEA level with a high tumor disappearance rate, which is determined by the ratio of the tumor area between the mediastinal and the lung windows on chest computed tomography, was recently shown to preoperatively predict the selection of a group of patients with peripheral adenocarcinoma that had no nodal metastasis [1Takamochi K, Nagai K, Yoshida J, et al. Pathologic N0 status in pulmonary adenocarcinoma is predictable by combining serum carcinoembryonic antigen level and computed tomographic findings? J Thorac Cardiovasc Surg 2001;122:325–30.Google Scholar]. This study from Okada and colleagues looking at the role of histology and smoking status on the prognostic value of CEA in patients with clinical stage I NSCLC reiterates the importance of CEA as an independent preoperative prognostic variable along with age, gender, and size of the tumor [2Okada M, Nishio W, Sakamoto T, et al. Effect of histologic type and smoking status on interpretation of serum carcinoembryonic antigen value in non–small cell lung carcinoma. Ann Thorac Surg 2004;78:1004–10.Google Scholar]. The authors eventually demonstrate that elevated preoperative CEA level had a predictive impact on prognosis only in nonsmokers with adenocarcinoma; this group also included previous smokers that had stopped smoking before their diagnosis of NSCLC. This finding may explain some of the discrepancies that were observed in the past and the low accuracy of elevated CEA level to predict outcome when it is indifferently applied to all patients with NSCLC. The importance of postoperative CEA level on outcome in patients with adenocarcinoma or squamous cell carcinoma and pathologically proven stage I disease is also briefly reported in the study. Unfortunately, the authors did not directly compare the outcome of patients that normalized their CEA level postoperatively to those that did not. However, the persistence of elevated CEA level despite apparently complete surgical resection is likely an important finding that is related to the persistence of undetected micrometastasis in mediastinal lymph nodes or elsewhere in the body. Hence, this group of patients is certainly at high risk of recurrence and could potentially benefit most from aggressive adjuvant chemotherapy. In conclusion, CEA is a tumor marker that may help to stratify patients with early stage NSCLC. The prognostic potential appears to be valid, mainly in nonsmokers or previous smokers, and it seems to be particularly useful in patients with adenocarcinoma. As the treatment of patients with early stage NSCLC is being refined in prospective studies, preoperative and postoperative CEA level appear to be an important factor to consider.

Postoperative serum carcinoembryonic antigen levels in patients with pathologic stage IA nonsmall cell lung carcinoma: subnormal levels as an indicator of favorable prognosis.

Elevated serum carcinoembryonic antigen (CEA) levels are sometimes attributable to the production of CEA by malignant cells, and in turn, the antigen itself can enhance the metastatic potential of malignant cells. The authors speculated that low serum CEA levels might be indicative of relatively low levels of malignant cells and a low probability of disease recurrence. This hypothesis led them to investigate whether low CEA levels in serum represented a useful prognostic factor for patients with pathologic Stage IA nonsmall cell lung carcinoma. Between 1993 and 2001, 724 patients underwent surgery for NSCLC at Toneyama National Hospital (Toyonaka, Japan). Of these patients, the 242 who were diagnosed with pathologic Stage IA disease were included in the current study. Smoking behavior, gender, age, tumor diameter, disease histology, and preoperative and postoperative serum CEA levels were chosen as study variables, with the cutoff level between subnormal and normal serum CEA levels set at 2.5 ng/mL and the cutoff level between normal and high serum CEA levels set at 5.0 ng/mL. Prognostic indicators were evaluated using a Cox hazard model. In addition, survival probabilities were calculated using the Kaplan-Meier method, and differences in survival were assessed by log-lank analysis. Subnormal postoperative serum CEA levels were found to be an independent prognostic indicator (hazard ratio, 2.3; 95% confidence interval, 1.1-4.7; P = 0.03 for comparison with patients who had normal CEA levels) on multivariate analysis. Furthermore, the 5-year survival rate was 87% for patients with subnormal postoperative CEA levels (n = 146), compared with 75% for patients with normal postoperative CEA levels (n = 80) and 53% for patients with high postoperative CEA levels (n = 16) (P < 0.0001). Among patients with pathologic Stage IA NSCLC, those who had an extremely favorable prognosis were distinguished by their subnormal postoperative serum CEA levels.

Prognosis of lung cancer patients with high preoperative carcinoembryonic antigen (CEA) level: Are they surgical candidates

7181 Background: Elevated preoperative serum carcinoembryonic antigen (CEA) level has been reported to be a poor prognostic factor in non-small cell lung cancer (NSCLC). Surgical indication remains controversial in clinical (c-) stage I NSCLC patients with very high CEA levels. Methods: Between Jan. 1985 and Dec. 2000, 1502 patients with c-stage I NSCLC underwent surgical resection at the National Cancer Center Hospital, Tokyo, Japan. They were retrospectively analyzed for preoerative CEA level, pathologic (p-) stage and postoperative prognosis. Patients were divided into three groups according to CEA levels: Group A (n=1077, CEA< 5.0ng/ml), Group B (n=394, 5.0 ≤ CEA < 50ng/ml), and Group C (n=31, 50ng/ml ≤ CEA). Results: The p-stages of the 1502 patients were: stage I in 909 patients (60.5%), stage II in 464 (30.9%), stage III in 52 (3.5%) and stage IV in 64(4.3%). Group C patients were significantly (P < 0.0001) upstaged post-operatively; among the 31 patients in Group C, 4 (12.9%) had p-stage II disease, 12 (38.7%) stage III, and 4 (12.9%) stage IV. Among the 1077/394 patients in Group A/B, 259 (24.0%) /175 (44.4%) were upstage to p-stage II or more, respectively. The 5-year survival was 81.8% in Group A (n=1077), 63.5% in Group B (n=394) and 28.2% in Group C (P < 0.0001). There were 7 long-term survivors (> 5 years) in Group C. Conclusions: Patients with high CEA levels (50ng/ml ≤) significantly had advanced disease in terms of p-stage. High CEA level was a poor prognostic factor. However, we did observe long term survivors in this group, and high CEA per se is not a contraindication for surgical resection after intensive preoperative evaluation. No significant financial relationships to disclose.