Normal Preoperative Carcinoembryonic Antigen Levels Research Articles

The time-dependent changes in serum carcinoembryonic antigen impact on posthepatectomy outcomes of colorectal liver metastasis

BackgroundOnly a few studies have examined the impact of carcinoembryonic antigen variation in patients before and after curative resection of colorectal liver metastasis . This study examined the correlation between carcinoembryonic antigen levels and patient prognosis. MethodsPatients who underwent curative resection for colorectal liver metastasis between 2000 and 2017 were enrolled. This study examined patients with high preoperative carcinoembryonic antigen levels that normalized after resection of colorectal liver metastasis and the correlation between prognosis and time-dependent changes in carcinoembryonic antigen levels. The similarity in the risk of recurrence in patients with normal preoperative carcinoembryonic antigen levels was evaluated. ResultsA total of 143 consecutive patients were included in the study cohort and classified into the normal preoperative (46 patients), normalized postoperative (57 patients), and elevated preoperative and postoperative (40 patients) carcinoembryonic antigen groups. All clinicopathologic characteristics were comparable between patients grouped according to carcinoembryonic antigen levels. The 5-year disease-free survival and overall survival rates for all patients were 30.4% and 56.0%, respectively. Multivariate analysis confirmed that elevated preoperative and postoperative carcinoembryonic antigen levels (hazard ratio = 1.73, 95% confidence interval: 1.04–2.87) were independently associated with poor disease-free survival; normalization of postoperative carcinoembryonic antigen (hazard ratio = 0.94, 95% confidence interval: 0.57–1.53) was statistically indistinguishable from normal preoperative carcinoembryonic antigen levels. The risk of recurrence was similar to that of patients with normal preoperative carcinoembryonic antigen levels ConclusionPatients with elevated preoperative carcinoembryonic antigen levels that normalized after resection of colorectal liver metastasis were not at risk of poor disease-free survival. Elevated carcinoembryonic antigen levels after surgery are independent prognostic factors for disease-free survival.

Postoperative carcinoembryonic antigen (CEA) levels predict outcomes after resection of colorectal cancer in patients with normal preoperative CEA levels.

BackgroundCarcinoembryonic antigen (CEA) is a cancer biomarker used in colorectal cancer (CRC) for tumor screening and outcome prediction. However it is still lack of sensitivity and specificity in general population. The present study aimed to investigate the clinical significance of CEA in patients with normal preoperative CEA levels.MethodsNinety-four patients were included who received surgery and developed an elevated CEA level postoperatively. They were divided into group A1 and A2 according to the peak CEA level (whether more than 10 ng/mL); group B1 and B2 according to CEA variation (whether reached a normal level at least once). The association between postoperative CEA and overall survival (OS), and disease-free survival (DFS) were analyzed using Kaplan-Meier method and Cox’s proportional hazards regression model.ResultsThe median follow-up time was 38 months. Patients in Group A2 and Group B2 had greater opportunities for recurrence and metastasis (P<0.05) compared to Group A1 and Group B1. Cox regression analysis revealed that high CEA levels and consistently elevated CEA levels were significantly associated with worse OS and DFS. Furthermore, patients with p-stage II in group A2 had worse OS than patients with p-stage III in group A1. The same result was detected when comparing group B2 and B1.ConclusionsAmong patients with an initially normal CEA level, postoperative CEA level and variation could be effective markers for tumor progression assessment. TNM stage, combined with CEA level might be more accurate in prognostic prediction.

Perioperative Serum Carcinoembryonic Antigen Ratio Is a Prognostic Indicator in Patients With Stage II Colorectal Cancer.

PurposeThe aim of this study was to evaluate whether the perioperative carcinoembryonic antigen (CEA) ratio could be used as a determinant for adjuvant therapy after curative surgery in stage II colorectal cancer.MethodsData for 119 patients with stage II colorectal cancer who underwent radical surgery between 2010 and 2013 were collected. The perioperative CEA ratio was defined as the postoperative/preoperative serum CEA level, and the patients were grouped according to their perioperative CEA ratios: high ratio (≥0.5) and low ratio (<0.5). Overall survival rates were calculated, and their prognostic significances were analyzed.ResultsThe overall survival rates of the high and the low perioperative CEA groups were 68.2% and 86.8%, respectively (P = 0.033). In patients with normal preoperative CEA levels (<5 ng/mL), the high perioperative CEA ratio group showed a worse survival rate than the low perioperative CEA ratio group (71.7% vs. 100.0%, P = 0.007). In patients with high preoperative CEA levels (≥5 ng/mL), the high perioperative CEA ratio group showed a worse survival rate than the low perioperative CEA ratio group (33.3% vs. 75.0%, P = 0.036). In the multivariate analysis, perioperative CEA ratio (P = 0.046), age (P = 0.034), and venous invasion (P = 0.015) were independent prognostic factors for survival.ConclusionThe perioperative CEA ratio is a prognostic indicator for stage II colorectal cancer. Patients with normal preoperative serum CEA levels might also be considered for adjuvant therapy if their perioperative CEA ratios are higher than 0.5.

Effect of adjuvant chemotherapy after pulmonary metastasectomy on the prognosis of colorectal cancer.

BackgroundAdjuvant chemotherapy after resection of colorectal cancer (CRC) lung metastases may reduce recurrences and improve survival. We investigated the effects of adjuvant chemotherapy after curative resection of lung CRC metastases on prognosis.MethodsWe retrospectively reviewed records of our patients undergoing pulmonary metastasectomy from CRC between January 2000–March 2014. Data were analyzed with Kaplan-Meier survival analysis and Cox proportional hazards models.ResultsOne-hundred (56 men; median age, 66 years) of 128 consecutive patients who underwent complete resection for first lung colorectal metastases were analyzed. Postoperative 5-year rates of overall survival (OS) and relapse-free survival (RFS) were 76% and 41%, respectively. Adjuvant chemotherapy strongly affected RFS and OS by multivariable analysis compared to surgery alone (RFS: HR, 0.49; 95% CI, 0.27–0.88; P = 0.016 and OS: HR, 0.35; 95% CI, 0.14–0.81; P = 0.014). Similar effects of adjuvant chemotherapy occurred in subgroups respectively classified according to number of lung metastases and preoperative serum carcinoembryonic antigen (CEA) level.ConclusionsAdjuvant chemotherapy after curative resection of lung metastases might strongly affect the prognosis of metastatic CRC patients. Even patients with single metastatic lesions and normal preoperative CEA level appeared to receive benefits from such chemotherapy. Narrowing of suitable candidates by predicting the effects of systemic chemotherapy and prospective randomized studies are needed.

The Significance of Serum Carcinoembryonic Antigen in Lung Adenocarcinoma.

BackgroundA raised carcinoembryonic antigen (CEA) may be associated with significant pathology during the postoperative follow-up of lung adenocarcinoma.MethodsWe reviewed the medical records of 305 patients who underwent surgical resections for primary lung adenocarcinoma at a single institution between April 2006 and February 2013.ResultsPreoperative CEA levels were significantly associated with age, smoking history, pathologic stage including pT (pathologic tumor stge), pN (pathologic nodal stage) and overall pathological stage, tumor size and differentiation, pathologically positive total lymph node, N1 and N2 lymph node, N2 nodal station (0/1/2=1.83/2.94/7.21 ng/mL, p=0.019), and 5-year disease-free survival (0.591 in group with normal preoperative CEA levels vs. 0.40 in group with high preoperative CEA levels, p=0.001). Preoperative CEA levels were significantly higher than postoperative CEA levels (p<0.001, Wilcoxon signed-rank test). Postoperative CEA level was also significantly associated with disease-free survival (p<0.001). A follow-up serum CEA value of >2.57 ng/mL was found to be the appropriate cutoff value for the prediction of cancer recurrence with sensitivity and specificity of 71.4% and 72.3%, respectively. Twenty percent of patients who had recurrence of disease had a CEA level elevated above this cutoff value prior to radiographic evidence of recurrence. Postoperative CEA, pathologic stage, differentiation, vascular invasion, and neoadjuvant therapy were identified as independent predictors of 5-year disease-free survival in a multivariate analysis.ConclusionThe follow-up CEA level can be a useful tool for detecting early recurrence undetected by postoperative imaging studies. The perioperative follow-up CEA levels may be helpful for providing personalized evaluation of lung adenocarcinoma.

Overall Survival of Stage III Colon Cancer with Only One Lymph Node Metastasis Is Independently Predicted by Preoperative Carcinoembryonic Antigen Level and Lymph Node Sampling Status.

BackgroundThis study identified predictors of favorable overall survival (OS) for stage III colon cancer patients who had only one lymph node (LN) metastasis (N1a).MethodsVariables, including preoperative carcinoembryonic antigen (CEA) level, LN sampling status, and the choices of postoperative adjuvant chemotherapy, were recorded. Prognostic significance was determined using the log-rank test and multivariate Cox regression analysis.ResultsThe median 42-month follow-up period included 363 eligible patients. Among them, 230 (63.3%) received only 5-flurouracil (5-FU) adjuvant chemotherapy; 76 (20.9%) underwent oxaliplatin-based regimens; and 57 (15.7%) chose surgery alone. The 5-year survival rate of these evaluated patients was 75%, 63%, and 77%, respectively (P = 0.823). Multivariate analysis revealed that normal preoperative CEA level (≦5 ng/mL) and adequate LN sampling (LN ≧ 12) were significant predictors for higher 5-year OS (P < 0.001; P = 0.007, respectively). However, the use of postoperative adjuvant chemotherapy in these N1a colon cancer patients did not significantly affect their 5-year OS.ConclusionsA preoperative CEA level of less than or equal to 5 ng/mL, and curative surgery with an adequate lymphadenectomy determined a favorable OS outcome in stage III colon cancer with only one LN metastasis.

The value of postoperative serum carcinoembryonic antigen and carbohydrate antigen 19-9 levels for the early detection of gastric cancer recurrence after curative resection.

PurposeThis study aimed to evaluate the value of serum carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) levels to detect gastric cancer recurrence.Materials and MethodsWe retrospectively reviewed 154 patients who developed recurrence within 2 years after curative gastric cancer surgery and analyzed the relationship between postoperative CEA and CA19-9 levels and recurrence. We readjusted the cut-off values to improve the detection of recurrence. Subgroup analysis according to clinicopathologic variables was performed to further investigate the relationship between recurrence and CEA and CA19-9 levels.ResultsThe sensitivity and specificity for elevated CEA levels to detect recurrence were 40.6% and 89.5%, respectively, and those for CA19-9 were 34.2% and 93.6%, respectively. The sensitivity and specificity for elevation of either tumor marker were 54.3% and 84.0%, respectively; those for elevation of both tumor markers were 19.2% and 98.4%, respectively. By readjusting the cut-off values from 5.0 ng/ml to 5.2 ng/ml for CEA and from 37.00 U/ml to 30.0 U/ml for CA19-9, the sensitivity was increased from 34.2% to 40.2% for CA19-9, while there was no increase in sensitivity for CEA. In subgroup analysis, the sensitivity of CEA was higher in patients with elevated preoperative CEA levels than in patients with normal preoperative CEA levels (86.7% versus 33.7%; P<0.001). Furthermore, the sensitivity of CA19-9 was higher in patients with elevated preoperative CA19-9 levels than in patients with normal preoperative CA19-9 levels (82.61% versus 26.83%; P<0.001).ConclusionsCEA and/or CA19-9 measurement with the readjusted cut-off values allows for more effective detection of gastric cancer recurrence.

Adjuvant Chemotherapy With or Without Pelvic Radiotherapy After Simultaneous Surgical Resection of Rectal Cancer With Liver Metastases: Analysis of Prognosis and Patterns of Recurrence

To investigate the outcomes of adjuvant chemotherapy (CT) or chemoradiotherapy (CRT) after simultaneous surgical resection in rectal cancer patients with liver metastases (LM). One hundred and eight patients receiving total mesorectal excision for rectal cancer and surgical resection for LM were reviewed. Forty-eight patients received adjuvant CRT, and 60 were administered CT alone. Recurrence patterns and prognosis were analyzed. Disease-free survival (DFS) and overall survival (OS) rates were compared between the CRT and CT groups. The inverse probability of the treatment-weighted (IPTW) method based on the propensity score was used to adjust for selection bias between the two groups. At a median follow-up period of 47.7 months, 77 (71.3%) patients had developed recurrences. The majority of recurrences (68.8%) occurred in distant organs. By contrast, the local recurrence rate was only 4.7%. Median DFS and OS were not significantly different between the CRT and CT groups. After applying the IPTW method, we observed no significant differences in terms of DFS (hazard ratio [HR], 1.347; 95% confidence interval [CI], 0.759-2.392; p = 0.309) and OS (HR, 1.413; CI, 0.752-2.653; p = 0.282). Multivariate analyses showed that unilobar distribution of LM and normal preoperative carcinoembryonic antigen level (<6 mg/mL) were significantly associated with longer DFS and OS. The local recurrence rate after simultaneous resection of rectal cancer with LM was relatively low. DFS and OS rates were not different between the adjuvant CRT and CT groups. Adjuvant CRT may have a limited role in this setting. Further prospective randomized studies are required to evaluate optimal adjuvant treatment in these patients.

Prognostic Significance of Perioperative Change of CEA Level in Colorectal Patients when Pre-Operative Level is Normal

The prognostic role of serum carcinoembryonic antigen (CEA) in colorectal cancer patients with normal preoperative level is questionable. We evaluate the perioperative change of serum CEA to elucidate its prognostic effect in these patients. We reviewed patients who received curative resection of colorectal cancer during 2000 and 2004 at Taipei Veterans General Hospital. The serum CEA level at diagnosis and one month after curative surgery were recorded. Levels higher than 5ng/mL were defined as abnormal. We divided patients with normal preoperative CEA level into two groups depending on the perioperative change. They were analyzed with clinicopathological factors and disease free survival rate. In patients with stage I to III colorectal cancer, there were 738 patients with normal preoperative CEA level (55.7%). Patients with increased post-operative CEA than pre-operative ones had higher percentage of colon cancer (p=0.007) and more lymphovascular invasion (p=0.038). Besides they also had higher disease recurrent rate (p=0.032) and worse disease-free survival (p=0.019). In multivariate analysis, perioperative CEA change, lymph node metastasis and tumor invasion depth remained independent prognostic factors (p=0.015). When preoperative CEA level is normal, perioperative change is a prognostic factor of colorectal cancer.

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.

Pulmonary resection for metastases from colorectal cancer: factors influencing prognosis. Twenty-year experience.

We reviewed our experience in the surgical management of 80 patients with colorectal pulmonary metastases and investigated factors affecting survival. From January 1980 to December 2000, 80 patients, 43 women and 37 men with median age 63 years (range 38-79 years) underwent 98 open surgical procedure (96 muscle-sparing thoracotomy, one clamshell and one median sternotomy) for pulmonary metastases from colorectal cancer (three pneumonectomy, 17 lobectomy, seven lobectomy plus wedge resection, six segmentectomy, three segmentectomy plus wedge resection and 62 wedge resection). Pulmonary metastases were identified at a median interval of 37.5 months (range 0-167) from primary colorectal resection. Second and third resections for recurrent metastases were done in seven and in four patients, respectively. Operative mortality rate was 2%. Overall, 5-year survival was 41.1%. Five-year survival was 43.6% for patients submitted to single metastasectomy and 34% for those submitted to multiple ones. Five-year survival was 55% for patients with disease-free interval (DFI) of 36 months or more, 38% for those with DFI of 0-11 months and 22.6% for those with DFI of 12-35 months (P=0.04). Five-year survival was 58.2% for patients with normal preoperative carcino-embryonic antigen (CEA) levels and 0% for those with pathologic ones (P=0.0001). Patients submitted to second-stage operation for recurrent local disease had 5-year survival rate of 50 vs. 41.1% of those submitted to single resection (P=0.326). Pulmonary resection for metastases from colorectal cancer may help survival in selected patients. Single metastasis, DFI>36 months, normal preoperative CEA levels are important prognostic factors. When feasible, re-operation is a safe procedure with satisfactory long-term results.

Pathologic N0 status in pulmonary adenocarcinoma is predictable by combining serum carcinoembryonic antigen level and computed tomographic findings

Objectives: It is not clear whether lymphadenectomy has therapeutic benefit in non–small cell lung cancer management. To avoid unnecessary lymphadenectomy, we attempted to identify clinical or radiologic predictors of pathologic N0 disease in patients with peripheral adenocarcinoma. Methods: From August 1992 through April 1997, 269 consecutive patients with peripheral adenocarcinoma who underwent major lung resection and systematic lymph node dissection were enrolled in this study. We reviewed their contrast-enhancement computed tomographic scans and recorded the maximum dimension of tumors both on pulmonary (pDmax) and on mediastinal (mDmax) window setting images, the largest dimension perpendicular to the maximum axis on both pulmonary (pDperp) and mediastinal (mDperp) window setting images, and the size of all detectable hilar-mediastinal lymph nodes. We defined a new radiologic parameter, tumor shadow disappearance rate (TDR), which is calculated with the following formula: TDR = 1 − (mDmax × mDperp)/(pDmax × pDperp). Results: In multivariable analysis a lower serum carcinoembryonic antigen level and a higher tumor shadow disappearance rate were significant predictors of pathologic N0 disease. Lymph node size on computed tomographic scanning was not a significant predictor. Among 59 patients with a normal preoperative carcinoembryonic antigen level and a tumor shadow disappearance rate of 0.8 or more, 58 (98%) patients had pathologic N0 disease, and the other patient had pathologic N1 disease. Conclusions: Mediastinal lymph node involvement was not found in patients with a normal preoperative serum carcinoembryonic antigen level and a tumor shadow disappearance rate 0.8 or more. The patients who meet these criteria may be successfully managed with major lung resection without systematic mediastinal lymphadenectomy.J Thorac Cardiovasc Surg 2001;122:325-30