Normal Preoperative Carcinoembryonic Antigen Research Articles

Dynamic monitoring of serum CEA and CA19-9 predicts the prognosis of postoperative stage II colon cancer

BackgroundWe sought to investigate the prognostic significance of carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) dynamics for stage II colon cancer patients undergoing radical resection. MethodsThis study retrospectively analyzed 1517 stage II colon cancer patients admitted to the Harbin Medical University Cancer Hospital from January 2011 to December 2016. To observe the relationship between tumor markers dynamic monitoring and survival, we calculated cut-off values for ΔCEA and ΔCA19-9. Group according to the cut-off values and compare the differences in survival between subgroups. ResultsPreoperative CA199 (HR = 3.122), postoperative CEA (HR = 2.941) and histological type (HR = 2.855) were independent prognostic factors in multivariate Cox proportional hazards models. The 5-year overall survival (OS) in the patients with normal preoperative CEA and CA19-9 was significantly better than the patients with elevated preoperative CEA or CA19-9 and the patients with elevated preoperative CEA and CA19-9 (92.6 % vs. 87.6 % vs. 81.0 %, P < 0.05). 469 patients with normal pre- and post-operative CEA had the highest 5-year OS (93.5 %, P < 0.05). Among the 177 patients with elevated pre- and post-operative CEA, the 5-year OS rate was only 81.8 % (P < 0.05). The cut-off values for Δ CEA and Δ CA19-9 in stage II colon cancer patients with elevated preoperative tumor markers were 2.625 ng/ml and 7.835 U/ml, respectively. The Kaplan-Meier curves showed that Δ CEA≥2.625 ng/ml and Δ CA19-9≥7.835 U/mL were associated with better outcome (87.8 % vs. 79.6 %, P < 0.05; 85.8 % vs. 79.1 %, P > 0.05). At the same time, we found that adjuvant chemotherapy significantly improved 5-year OS in patients with elevated preoperative CEA or CA19-9 (91.0 % vs. 80.9 % and 89.6 % vs. 80.2 %, P < 0.05). ConclusionsPersistent postoperative elevation of CEA/CA19-9 is associated with a poor prognosis. CEA and CA19–9 may be high-risk factors for postoperative adjuvant therapy in stage II colon cancer patients. For stage II colon cancer patients with elevated preoperative CEA, patients with Δ CEA<2.625 ng/ml have poor survival and can improve prognosis by receiving adjuvant therapy.

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.

Clinical Associations of Preoperative and Postoperative Serum CEA and Lung Cancer Outcome.

Background: Serum carcinoembryonic antigen (CEA), a classic tumour marker, is widely used in lung cancer in clinical practice. Nevertheless, few studies have elucidated the influence of dynamic changes in CEA in the perioperative phases, as a prognostic indicator, on lung cancer prognosis. Methods: This retrospective cohort analysis included consecutive patients with stage I-III lung cancer who underwent curative resection between December 2010 and December 2014. The patients were grouped into three cohorts: group A included patients with normal preoperative CEA, group B included patients with elevated preoperative CEA but normal postoperative CEA, and group C included patients with elevated preoperative and postoperative CEA. Five-year overall survival (OS) was estimated by Kaplan-Meier analysis (log-rank test). Multivariate analyses were performed with Cox proportional hazard regression. Results: A total of 1662 patients with stage I-III lung cancer were enrolled in our study. Patients with normal preoperative CEA had 15.9 and 20.1% better 3- and 5-year OS rates than the cohort with elevated preoperative CEA (p < 0.001). Furthermore, group C had 36.0 and 26.6% lower 5-year OS rates (n = 74, 32.4%) than group A (n = 1188, 68.4%) and group B (n = 139, 59.0%) (p < 0.001). Group B had poorer OS than group A (p = 0.016). For patients with different pathological TNM stages, subgroup analyses showed that group C had the shortest OS in stages I and II (p < 0.05), and patients with a post-preoperative CEA increment had poorer OS than those without an increment (p = 0.029). Multivariate analyses suggested that group C (HR = 2.0, 95% CI, 1.5–2.7, p < 0.001) rather than the group with normalized postoperative CEA (HR = 1.2, 95% CI, 0.9–1.5, p = 0.270) was an independent prognostic factor. In subgroup analysis of adenocarcinoma (ADC), survival analyses suggested that group C predicted a worse prognosis. Multivariate analysis of ADC indicated that group C was an independent adverse prognostic factor (HR = 1.9, 95% CI, 1.4–2.7, p < 0.001). Conclusions: Combined elevated preoperative and postoperative CEA is an independent adverse prognostic factor for stage I-III lung adenocarcinoma. Additionally, routine perioperative detection of serum CEA can yield valuable prognostic information for patients after lung cancer surgery.

Association of Preoperative Serum Carcinoembryonic Antigen and Gastric Cancer Recurrence: A Large Cohort Study.

Background and Aim: Measuring postoperative carcinoembryonic antigen (CEA) is recommended by guidelines to help detecting recurrence of gastric cancer patients. However, the prognostic significance of elevated preoperative CEA is unclear. This study aims to investigate whether patients with elevated preoperative CEA have a higher risk of recurrence than patients with normal preoperative CEA.Methods: We conducted a retrospective cohort study at a gastric cancer center in South China. Consecutive patients with stage I to III gastric adenocarcinoma who underwent curative resection at the center from January 2001 to February 2016 were identified. Patients were grouped into two cohorts: normal preoperative CEA (≤ 5 ng/ml), and elevated preoperative CEA (> 5 ng/ml). 3-year recurrence-free survival (RFS) and hazard function curves over time were estimated.Results: A total of 1,596 patients (1,063 {66.6%} male; median {Interquartile range, IQR} age, 59 {50-66} years) were identified. Patients with elevated preoperative CEA had 15.5% lower 3-year RFS (n=222 {70.4%}) than the cohorts with normal preoperative CEA (n=1,374 {85.9%}). The hazard function of recurrence for the two cohorts peaked at the similar time (around 10 months after surgery). Multivariate Cox analyses confirmed that elevated preoperative CEA was independently associated with shorter RFS (Hazard Ratio {HR}, 1.69; 95% confidence interval {CI}, 1.26-2.27; P = 0.001).Conclusions: Patients with elevated preoperative CEA are at increased risk for recurrence, especially within the first 24 months after surgery.

Selection of Pathological N0 (pN0) in Clinical IA (cIA) Lung Adenocarcinoma by Imaging Findings of the Main Tumor

Objectives: We would like to clarify the imaging findings of the main tumor that may omit the requirement for lymph node dissection in clinical IA (cIA) lung adenocarcinoma.Methods: A total of 336 patients with cIA lung adenocarcinomas with normal preoperative carcinoembryonic antigen (CEA) who underwent surgical resection were analyzed. We investigated the association between various computed tomography (CT) imaging findings or the maximum standardized uptake value (SUVmax) of fluorodeoxyglucose-position emission tomography (FDG-PET) and lymph node metastasis. The maximum tumor diameter was calculated from the CT images using both the lung window setting (LD) and mediastinal window setting (MD). The diameter of the solid component (CD) was defined as consolidation diameter in lung window setting. The solid component ratio (C/T) was defined as CD/LD.Results: SUVmax, MD, and C/T were independent factors related to lymph node metastasis, but CD was not (p = 0.38). The conditions required for the positive predictive value (PPV) to reach 100% were 10.6 mm for MD, 12.5 mm for CD, and 0.55 for C/T. SUVmax did not reach 100%.Conclusions: In cIA lung adenocarcinoma with CEA in the normal range, we found that it may be possible for lymph node dissection to be omitted by MD, CD, and C/T.

Clinical Significance of Preoperative Serum Carcinoembryonic Antigen Within the Normal Range in Colorectal Cancer Patients Undergoing Curative Resection.

Serum carcinoembryonic antigen (CEA) is a widely used tumor marker in colorectal cancer (CRC), but within normal range of preoperative CEA levels the clinical significance of CEA is unknown. The aim of this study was to evaluate the usefulness of CEA within the normal range as a prognosticator of non-metastatic CRC. This retrospective cohort study included 2021 CRC patients with normal preoperative CEA who underwent elective curative surgery (discovery group). We determined the optimal cut-off value for disease-free survival (DFS) discrimination using the Contal and O'Quigley method. We also assessed the prognostic significance of the cut-off value in a prospective cohort of 171 stage III colon cancer patients treated with oxaliplatin-based adjuvant chemotherapy (validation group). The optimal cut-off CEA value was 2.1ng/mL in the discovery group. The DFS rates were significantly poorer in patients with high-normal preoperative CEA levels (2.1-5.0ng/mL) than in those with low-normal CEA levels (< 2.1ng/mL) in both groups. A high-normal CEA level was an independent risk factor for DFS in both groups, and was associated with inferior DFS in patients with stage II and III disease and in never or former smokers. The correlation between DFS and CEA levels was more distinct in left-sided colon and rectal cancer. A high-normal preoperative CEA level (≥ 2.1ng/mL), even within the normal range, was an independent prognosticator for poor DFS in CRC. The usefulness of CEA was influenced by smoking status and tumor location in addition to tumor stage.

THE Role of Preoperative carcinoembryonic antigen in recurrence of resectable colorectal carcinoma.

SUMMARYIn colorectal carcinoma, carcinoembryonic antigen (CEA) is a recommended marker for surveillance after curative resection. The aim of the present study was to determine the association of preoperative CEA with recurrence of colorectal carcinoma in our population. The study included 55 patients with all operable stages of colorectal adenocarcinoma treated during the 2012-2014 period, evaluated retrospectively and followed-up for recurrence for 2 years. Data on the baseline (preoperative) CEA levels were retrieved from patient files. On data analysis, SPSS 16.0 was used. In patients with normal preoperative CEA, the rate of recurrence was significantly low (p=0.008) and the likelihood of no recurrence 1.55-fold greater as compared to patients with raised initial CEA levels (p=0.028). In patients with raised preoperative CEA, the risk of recurrence was 5.26-fold greater as compared to those with normal CEA levels (p=0.028). A significant weak positive correlation (rs=0.297) was found between raised CEA and recurrence. A highly significant (p=0.002) moderate positive correlation was recorded in patients aged <50 and moderate positive correlation of borderline significance in males (rs=0.324, p=0.058). Sensitivity was 94.4% and specificity 32.4% in predicting recurrence. Accordingly, preoperative elevated CEA showed a significant weak positive correlation with recurrence while normal preoperative CEA moderately decreased the likelihood of recurrence.

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.

Prognostic impact of preoperatively elevated and postoperatively normalized carcinoembryonic antigen levels following curative resection of stage I-III rectal cancer.

BackgroundPreoperative and early postoperative serum carcinoembryonic antigen (CEA) levels are known prognostic factors in rectal cancer. Recently, a large‐scale study on colon cancer revealed that “preoperatively elevated and postoperatively normalized CEA levels” is not an indicator of poor prognosis. However, whether this hold true in rectal cancer patients is unknown. This study aimed to investigate the prognostic significance of preoperatively elevated and postoperatively normalized CEA levels in rectal cancer patients undergoing curative resection.MethodsSubjects were consecutive stage I‐III rectal cancer patients who underwent curative resection without preoperative treatment at National Cancer Center Hospital between 2000 and 2015. Overall survival (OS) and the hazard function of recurrence or death were analyzed according to the CEA levels, as follows: normal preoperative CEA (normal group), preoperatively elevated but postoperatively normalized CEA (normalized group), and preoperatively and postoperatively elevated CEA (elevated group).ResultsThe normalized group (n =235) had worse OS (HR 1.49, 95% CI 1.08‐2.04; P = .0142) compared to the normal group (n = 1208), and better OS compared to the elevated group (n = 47) (HR 0.53, 95% CI 0.31‐0.91; P = .0208). The elevated group had the highest and earliest peak in hazard function, followed by the normalized group and the normal group, with median times to recurrence of 8.8, 15.5, and 18.5 months, respectively (P = .0223).ConclusionsPrognosis after resection of rectal cancer was worse in patients with preoperatively elevated and postoperatively normalized CEA compared to those with normal preoperative CEA. Patients with elevated preoperative CEA might require intensive follow‐up even if levels normalize after resection, especially in earlier periods, for early detection of recurrence.

Controlling Nutritional Status (CONUT) as a prognostic immunonutritional biomarker for gastric cancer after curative gastrectomy: a propensity score-matched analysis.

In clinical practice, it is not unusual to treat oncologic patients whose tumor markers are within normal range, even with advanced cancer. The Controlling Nutritional Status (CONUT) score could provide a useful nutritional and immunological prognostic biomarker for cancer patients. In this study, we assessed the prognostic value of the CONUT score for patients with gastric cancer, including a subgroup analysis with stratification based on serum carcinoembryonic antigen (CEA) level. We retrospectively reviewed the medical records of 368 consecutive patients who underwent curative laparoscopy-assisted gastrectomy. The prognostic value of the CONUT score was compared between patients with a low (≤ 2) and high (≥ 3) score, with propensity score matching (PSM) used to control for biasing covariates (Depth of tumor, Lymph node metastasis, pathological TNM (pTNM) stage). Overall survival (OS) among all patients was independently predicted by the tumor stage (hazard ratio (HR): 2.231, p = 0.001), the CONUT score (HR: 2.254, p = 0.001), and serum CEA level (HR: 1.821, p = 0.025). Among patients with a normal preoperative serum CEA level, tumor stage (HR: 2.350, p = 0.007), and the CONUT score (HR: 1.990, p = 0.028) were independent prognostic factors of OS. In the high serum CEA level group, tumor size (HR: 2.930, p = 0.015) and the CONUT score (HR: 3.707, p = 0.004) were independent prognostic factors of OS. It is advantageous to use both CEA level and the CONUT score to assess the prognosis of patients with gastric cancer, which reflect both tumor-related factors and host-related factors, respectively.

134P - A retrospective analysis of the association between perioperative carcinoembryonic antigen level and prognosis in stage III colorectal cancer

Abstract Background Carcinoembryonic antigen (CEA) is the most widespread tumour marker of colorectal cancer, however, it is not helpful to judge for recurrence of the disease because of low sensitivity and specificity. It is recommended for patients who were diagnosed with pStage III colorectal cancer to receive adjuvant chemotherapy after curative resection and to measure CEA every 3 months. Moreover, It is reported that postoperative CEA level is more informative than preoperative CEA level about the impact for prognosis but the association between postoperative, post adjuvant CEA level and the prognosis is still unclear. This study aimed to evaluate whether perioperative and post adjuvant CEA level was useful for estimation of the prognosis in stage III CRC. Methods This retrospective study was conducted at the Cancer Institute Hospital of JFCR. A total of 567 consecutive patients who underwent curative resection for stage III colon adenocarcinoma and adjuvant chemotherapy in our hospital from March 2005 to December 2013 were identified. The patients who received bevacizumab as adjuvant chemotherapy and didn’t measure CEA were excluded. Results The 3-year DFS rate in patients with normal preoperative CEA is superior to patients with high preoperative CEA (HR:1.59;95%CI:1.10-2.31, p = 0.014). There was no significant difference in the 5-year OD between the two groups (HR1.17;95%CI:0.62–2.20, p = 0.63). The 3-year DFS rate and 5-year OS rate in patients with normal postoperative CEA were superior to patients with high postoperative CEA (HR:2.18;95%CI:1.23–3.88, p = 0.0079, and HR:2.40;95%CI:1.02–5.69, p = 0.046). The 3-year DFS in patients with normal postadjuvant CEA was superior to patients with high postadjuvant CEA(HR1.79;95%CI:1.23–3.88, p = 0.022), whereas regarding the 5-year OS there was no significant difference between the two groups (HR2.10;95%CI:0.98–4.53, p = 0.057).In the multivariate analysis, the histological type and N-stage were predictive factors of OS. Conclusions High postoperative and post adjuvant CEA level may be negative prognosis factors for OS in patients who underwent curative resection for stage III CRC. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.

Prognostic nutritional index as a predictor of survival in resectable gastric cancer patients with normal preoperative serum carcinoembryonic antigen levels: a propensity score matching analysis

BackgroundAn ideal tumor marker should be capable of being detected at any stage of the disease. However, gastric cancer patients do not always have elevated serum carcinoembryonic antigen (CEA) levels, even in advanced cases. Recently, several studies have investigated the associations between preoperative PNI and postoperative long-term outcomes. In this study, we focused on the significance of the prognostic nutritional index (PNI) as a potential predictor of survival in resectable gastric cancer patients with normal preoperative serum CEA levels.MethodsWe retrospectively conducted cohort study to evaluate the PNI as a predictor of survival in 368 resectable gastric cancer patients who underwent potentially curative gastrectomy at our institute between January 2010 and December 2016. We selected 218 patients by propensity score matching to reduce biases due to the different distributions of co-variables among the comparable groups.ResultsIn the multivariate analysis, pStage (hazard ratio [HR]: 14.003, 95% confidence interval [CI]: 5.033–44.487; p < 0.001), PNI (HR: 2.794, 95% CI: 1.352–6.039; p < 0.001) were identified as independent prognostic factors of CSS in 218 propensity matched gastric cancer patients. The Kaplan-Meier analysis demonstrated that low PNI patients had a significantly poorer cancer specific survival (CSS) than high PNI patients (p = 0.008).Among 166 propensity matched gastric cancer patients with normal preoperative serum CEA levels, multivariate analysis demonstrated that pStage (HR: 7.803, 95% CI: 3.015–24.041; p < 0.001) and PNI (HR: 3.078, 95% CI: 1.232–8.707; p = 0.016) were identified as independent prognostic factors of CSS. And Kaplan-Meier analysis demonstrated that low PNI had a significantly poorer CSS than high PNI value (p = 0.011).ConclusionsThis study demonstrates that a low preoperative PNI value is a potential independent risk factor for poorer CSS in patients with gastric cancer, even in those with normal serum CEA levels.

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.

Association of Preoperative and Postoperative Serum Carcinoembryonic Antigen and Colon Cancer Outcome

Guidelines recommend measuring preoperative carcinoembryonic antigen (CEA) in patients with colon cancer. Although persistently elevated CEA after surgery has been associated with increased risk for metastatic disease, prognostic significance of elevated preoperative CEA that normalized after resection is unknown. To investigate whether patients with elevated preoperative CEA that normalizes after colon cancer resection have a higher risk of recurrence than patients with normal preoperative CEA. This retrospective cohort analysis was conducted at a comprehensive cancer center. Consecutive patients with colon cancer who underwent curative resection for stage I to III colon adenocarcinoma at the center from January 2007 to December 2014 were identified. Patients were grouped into 3 cohorts: normal preoperative CEA, elevated preoperative but normalized postoperative CEA, and elevated preoperative and postoperative CEA. Three-year recurrence-free survival (RFS) and hazard function curves over time were analyzed. A total of 1027 patients (461 [50.4%] male; median [IQR] age, 64 [53-75] years) were identified. Patients with normal preoperative CEA had 7.4% higher 3-year RFS (n = 715 [89.7%]) than the combined cohorts with elevated preoperative CEA (n = 312 [82.3%]) (P = .01) but had RFS similar to that of patients with normalized postoperative CEA (n = 142 [87.9%]) (P = .86). Patients with elevated postoperative CEA had 14.9% lower RFS (n = 57 [74.5%]) than the combined cohorts with normal postoperative CEA (n = 857 [89.4%]) (P = .001). The hazard function of recurrence for elevated postoperative CEA peaked earlier than for the other cohorts. Multivariate analyses confirmed that elevated postoperative CEA (hazard ratio [HR], 2.0; 95% CI, 1.1-3.5), but not normalized postoperative CEA (HR, 0.77; 95% CI, 0.45-1.30), was independently associated with shorter RFS. Elevated preoperative CEA that normalizes after resection is not an indicator of poor prognosis. Routine measurement of postoperative, rather than preoperative, CEA is warranted. Patients with elevated postoperative CEA are at increased risk for recurrence, especially within the first 12 months after surgery.

High cripto-1 and low miR-205 expression levels as prognostic markers in early stage non-small cell lung cancer

ObjectivesCripto-1 (CR-1) plays a critical role in the activation of SMAD, SRC, and epithelial-to-mesenchymal transition (EMT) pathways and has been shown to be prognostic in several cancer types. In addition, we showed that CR-1 renders EGFR-mutated NSCLC cells resistant to EGFR-TKI through the activation of SRC and EMT via miR-205 downregulation. This study aimed to investigate the correlation between expression of CR-1 and miR-205 and prognosis of NSCLC patients with or without EGFR mutations. Materials and methodsA total of 265 patients with stage I (AJCC 6th edition) radically resected NSCLC were tested for CR-1 expression and EGFR mutations by immunohistochemistry and miR-205 expression via qPCR assay. ResultsCR-1 expression was evaluated with immunohistochemistry using a tissue microarray on 265 T1-2N0 surgical NSCLC samples. Of the 265 tumors, 250 (94%) expressed various levels of CR-1. A significant inverse correlation was identified between expression of miR-205 and CR-1. NSCLC patients (T1N0, n = 106) with high CR-1 expression had worse prognosis (shorter recurrence-free survival, p = .045) than those with low CR-1 expression. A similar trend was observed in NSCLC patients with normal preoperative carcinoembryonic antigen (CEA) levels (serum CEA levels <5 ng/ml; n = 179; p = .085); however, no significant correlation was found between CR-1 expression and survival rate in the T2N0 or high CEA groups. In addition, NSCLC patients with low miR-205 expression (n = 126) had poorer prognosis in terms of recurrence than those with high miR-205 expression (n = 127; p = .001). ConclusionHigh CR-1 expression is correlated with poor prognosis in NSCLC with low tumor burden and may be used to select high-risk patients for adjuvant chemotherapy in early NSCLC. Moreover, low miR-205 expression likely related to high CR-1 expression could be a prognostic marker for patients with NSCLC.

Prognostic Value of Preoperative Serum Carcinoembryonic Antigen and Carbohydrate Antigen 19-9 After Resection of Ampullary Cancer

BackgroundThe purpose of this study is to investigate the prognostic value of pre-resection serum carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 after resection of ampullary cancer (AC) in consideration of intestinal (IT) and pancreatobiliary (PT) subtypes. MethodsOverall survival (OS) analysis of patients undergoing curative resection of ampullary cancer. ResultsElevated preoperative CEA (P = 0.013) and CA 19-9 levels (P = 0.030) were significant prognostic factors. Subgroup analysis, however, showed both markers having prognostic value only for the IT subgroup. Pre-resection CEA within normal range identified a subgroup of IT patients with an excellent median survival of 145 months. Compared to other AC patients, this low-risk ITCEA− subpopulation was characterized by less frequent advanced pT stages (pT3/pT4, 41 vs. 62%; P = 0.047) and lymph node involvement (pN+, 30 vs. 65%; P = 0.001). OS of this subgroup was significantly better compared to other AC patients (145 vs. 25 months; HR = 3.8; P < 0.001). By multivariate survival analysis, the patient age, the PT subtype, and an elevated pre-resection serum CEA value were identified as independent prognostic variables. ConclusionsIn AC, the histomorphologic subclassification is highly relevant regarding the prognostic value of preoperative serum CEA and CA 19-9. IT-patients with normal preoperative CEA represent a favorable subgroup with excellent long-term survival.

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.

Inflammation-based prognostic system predicts postoperative survival of esophageal carcinoma patients with normal preoperative serum carcinoembryonic antigen and squamous cell carcinoma antigen levels.

BackgroundThe Glasgow Prognostic Score (GPS) is an established inflammation-based system that is used to predict the prognosis for several types of malignancies. In this retrospective study, we assessed the postoperative survival of 725 patients with non-metastatic esophageal squamous cell carcinoma who had normal preoperative serum tumor marker levels according to the GPS.MethodsAmong 1394 patients who underwent esophagectomy between August 2006 and December 2010, 725 with normal preoperative serum levels of carcinoembryonic antigen (CEA) and squamous cell carcinoma antigen (SCC-Ag) were enrolled. All demographic, pathologic, and survival data were analyzed retrospectively. Uni- and multivariate analyses were performed to evaluate the relationship with overall survival. The Kaplan–Meier analysis and log-rank tests were used to compare the survival curves between patients with GPS 0 (group A) and 1 or 2 (group B).ResultsPatients in group A exhibited significantly better 3- and 5-year cancer-specific survival (CSS) rates (0.780 and 0.759, respectively) than those in group B (0.624 and 0.605, respectively). Multivariate Cox regression analysis revealed that age, tumor length, pathological tumor-node-metastasis (pTNM) stage, venous invasion, lymph node metastasis, serum albumin and C-reactive protein levels, and GPS were associated with postoperative survival of these patients. Further multivariate analysis confirmed that GPS was an independent prognostic factor. The Kaplan–Meier analysis and log-rank tests demonstrated a significant difference in CSS between groups A and B (P = 0.001).ConclusionsGPS may be a valuable prognostic indicator for esophageal cancer patients with normal preoperative CEA and SCC-Ag serum levels.

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.