Elevated Postoperative Carcinoembryonic Antigen Research Articles

Elevated postoperative carcinoembryonic antigen guides adjuvant chemotherapy for stage II colon cancer: a multicentre cohort retrospective study

Most clinical doctors rely on high-risk factors recommended by guidelines to decide whether to undergo adjuvant chemotherapy for stage II colon cancer. However, these high-risk factors do not include postoperative carcinoembryonic antigen (CEA). This study aims to explore the elevation of postoperative CEA as a risk factor, in addition to other high-risk factors, to guide adjuvant chemotherapy for patients with stage II colon cancer. A retrospective analysis was conducted on stage II colon cancer patients who underwent curative surgery at Yunnan Cancer Hospital and The Sixth Affiliated Hospital of Sun Yat-Sen University from April 2008 to January 2019. Patients were classified into three groups based on high-risk factors recommended by guidelines and postoperative CEA levels: low-risk with normal postoperative CEA, low-risk with elevated postoperative CEA and high-risk. COX regression analysis was used to identify independent prognostic factors affecting patients’ recurrence free survival (RFS). The Kaplan–Meier method was used to create the patients’ RFS curve. The restricted cubic spline (RCS) curve was used to assess the correlation between postoperative CEA and RFS on a continuous scale. Among 761 patients, there were 444 males (62.01%), with a median [IQR] age of 58.0 (18.0–88.0) years. A group of 425 high-risk patients had a 3-year RFS of 82.2% (95% CI 78.5–86.1%), while a group of 291 low-risk patients had a 3-year RFS of 89.7% (95% CI 86.1–93.5%). There was a statistically significant difference between the two groups (HR 1.83; 95% CI 1.22–2.74; P = 0.0067). Among them, the 3-year RFS of 261 low-risk patients with normal postoperative CEA was 93.6% (95% CI 90.5–96.8%), while the 3-year RFS of 30 low-risk patients with elevated postoperative CEA was 57.3% (95% CI 41.8–71.4%). There was a significant difference compared to the 3-year RFS of 425 high-risk patients (overall log-rank P < 0.0001). The multivariate analysis adjusted by the COX proportional hazards model showed that low-risk patients with elevated postoperative CEA patients (HR 14.95, 95% CI 4.51–49.63, P < 0.0001) was independently associated with a 3-year RFS. The restricted cubic spline model showed that in stage II colon cancer patients with tumor diameter > 1.955 ng/mL, the risk of postoperative recurrence increased with increasing postoperative CEA levels. Patients with elevated postoperative CEA levels have a significantly increased risk of recurrence. They should be included as high-risk factors to guide adjuvant chemotherapy for stage II colon cancer.

Postoperative serum squamous cell carcinoma antigen and carcinoembryonic antigen predict overall survival in surgical patients with esophageal squamous cell carcinoma.

Tumor markers are routinely used in clinical practice. However, for resectable patients with esophageal squamous cell carcinoma (ESCC), they are applied infrequently as their prognostic significance is incompletely understood. This historical cohort study included 2769 patients with resected ESCC from 2011 to 2018 in a high-risk area in northern China. Their clinical data were extracted from the Electronic Medical Record. Survival analysis of eight common tumor markers was performed with multivariable Cox proportional hazards regressions. With a median follow-up of 39.5 months, 901 deaths occurred. Among the eight target markers, elevated postoperative serum SCC (Squamous cell carcinoma antigen) and CEA (Carcinoembryonic antigen) predicted poor overall survival (SCC HRadjusted: 2.67, 95% CI: 1.70-4.17; CEA HRadjusted: 2.36, 95% CI: 1.14-4.86). In contrast, preoperative levels were not significantly associated with survival. Stratified analysis also demonstrated poorer survival in seropositive groups of postoperative SCC and CEA within each TNM stage. The above associations were generally robust using different quantiles of concentrations above the upper limit of the clinical normal range as alternative cutoffs. Regarding temporal trends of serum levels, SCC and CEA were similar. Their concentrations fell rapidly after surgery and thereafter remained relatively stable. Postoperative serum SCC and CEA levels predict the overall survival of ESCC surgical patients. More importance should be attached to the use of these markers in clinical applications.

Postoperative serum carcinoembryonic antigen levels cannot predict survival in colorectal cancer patients with type II diabetes

Background:Most clinical guidelines recommend measuring postoperative carcinoembryonic antigen (CEA) levels to predict the prognosis of colorectal cancer. However, type II diabetes can increase serum CEA levels which may bias the prognosis. Thus, we aimed to evaluate the impact of type II diabetes on CEA prognostic accuracy in colorectal cancer.Methods:This retrospective cohort study included 407 patients who underwent curative resection for stage I to III colorectal adenocarcinoma in a single institution between January 2010 and June 2018. The patients were categorized into two groups according to their postoperative serum CEA levels: group A <5.0 ng/mL (n = 341) and group B ≥5.0 ng/mL (n = 66). Patients were also categorized into two subgroups according to their history of type II diabetes: patients with type II diabetes mellitus (n = 112) and patients without type II diabetes (n = 295).Results:The 3-year disease-free survival (DFS) rates were significantly higher in patients with normal postoperative CEA (group A, 83.8%) than in patients with elevated preoperative and postoperative CEA (group B, 63.6%) (p < 0.001). However, although patients with type II diabetes mellitus had higher postoperative CEA levels than those without type II diabetes mellitus (3.1 vs 2.5 ng/mL, p < 0.001), group B patients with type II diabetes mellitus had a significantly higher 3-year DFS rate than those without type II diabetes mellitus (80.0% vs 55.6%, p = 0.003).Conclusion:Type II diabetes was associated with higher preoperative and postoperative CEA levels in patients with colorectal cancer. Consequently, elevated postoperative CEA level was not associated with shorter 3-year DFS in patients with type II diabetes, as opposed to patients without type II diabetes. Therefore, colorectal cancer patients with type II diabetes may need alternative tumor markers to be used during the surveillance strategy after curative surgery.

Postoperative serum CA19-9, YKL-40, CRP and IL-6 in combination with CEA as prognostic markers for recurrence and survival in colorectal cancer

Background In colorectal cancer (CRC) patients, guidelines only recommend measurement of preoperative carcinoembryonic antigen (CEA), although postoperative CEA may be more informative. However, the sensitivity of both preoperative and postoperative CEA in identifying relapse is limited. We studied whether CA19-9, YKL-40, C-reactive protein (CRP) and interleukin (IL)-6 add prognostic information combined with postoperative CEA. Material and methods This post-hoc analysis included 147 radically resected stage II (n = 38), III (n = 91) and IV (n = 18) CRC patients treated with adjuvant 5-fluorouracil (5-FU)-based therapy in the phase III LIPSYT study (ISRCTN98405441). We collected postoperative blood samples a median of 48 days after surgery. We analysed relapses, sensitivity, positive predictive value (PPV) and disease-free (DFS) and overall survival (OS) by bootstrap, Kaplan–Meier and adjusted Cox-models in the elevated vs. normal biomarker groups. Results Elevated postoperative CEA associated with impaired DFS (HR 7.23; CI95% 3.85–13.58), impaired OS (HR 7.16; CI95% 3.76–13.63), and more relapses (HR 7.9; CI95% 3.4–18.2); but sensitivity for CEA in finding relapses was only 31% (CI95% 21–48%). Normal CEA combined with an elevated YKL-40 or elevated CRP showed more relapses (HR for YKL-40 2.13 [CI95% 1.10–4.13], HR for CRP 3.14 [CI95% 1.21–8.16]), impaired DFS (HR 2.18 [CI95% 1.12–4.24] or 3.23 [CI95% 1.34–7.82]), and impaired OS (2.33 [CI95%1.24–4.40] or 2.68 [CI95%1.12–6.44]). Elevated CEA combined with a concomitantly elevated CA19-9, YKL-40, CRP or IL-6 showed a respective PPV of 100, 90, 100, and 100%. Conclusion In radically operated stage II to IV CRC patients who received adjuvant 5-FU-based chemotherapy, a postoperatively elevated CEA alone or in combination with CA19-9, YKL-40, CRP, or IL-6, or a normal CEA combined with an elevated YKL-40 or with an elevated CRP, may indicate patients at high risk of relapse.

Prognostic value of postoperative serum carcinoembryonic antigen levels in colorectal cancer patients with chronic kidney disease

BackgroundChronic kidney disease (CKD) can increase serum carcinoembryonic antigen (CEA) levels. We thus aimed to evaluate the impact of CKD on CEA prognostic accuracy in colorectal cancer. MethodsAltogether, 429 patients who underwent curative resection for stages I–III colorectal adenocarcinoma were grouped according to postoperative CEA levels and history of CKD. ResultsThree-year disease-free survival (DFS) was higher in patients with normal postoperative CEA (group A, 83.4%) than in those with elevated postoperative CEA (group B, 64.3%) (p < 0.001). CKD patients had higher postoperative CEA levels than non-CKD patients (odds ratio 3.27, 95% confidence interval 1.78–5.99, p < 0.001). In multivariable analysis, postoperative CEA level was an independent prognostic factor for DFS in non-CKD, but not CKD, patients. ConclusionsCKD can increase postoperative CEA levels in colorectal cancer patients. Elevated postoperative CEA levels were associated with shorter DFS in non-CKD, but not CKD, patients.

Prognostic value of postoperative serum carcinoembryonic antigen levels in colorectal cancer patients who smoke.

Serum carcinoembryonic antigen (CEA) levels can help predict the prognosis of colorectal cancer patients. Accordingly, high preoperative CEA levels that is not restored after surgery are indicative of a worse outcome. On the other hand, smoking can increase serum CEA levels independently of the disease status. Thus, we aimed to evaluate the impact of smoking on the prognostic value of serum CEA levels. This retrospective cohort study included 273 patients who underwent curative resection for stage I-III colorectal adenocarcinoma at a single institution, between January 2010 and December 2017. Patients were grouped as follows: group A, normal preoperative and postoperative CEA levels (n = 152); group B, elevated preoperative CEA levels that returned to reference values after surgery (n = 69); and group C, elevated postoperative serum CEA levels (n = 52). Patients were also grouped according to their smoking history: group S (current smokers, n = 79) and group NS (never and former smokers, n = 194). Group A showed a higher 3-year disease-free survival (DFS) rate (84.9%) than groups B (75.4%) and C (62.0%) (p < 0.001). Postoperative serum CEA levels were significantly higher in the S group than in the NS group (2.6 vs. 3.1 ng/mL, p = 0.009), whereas preoperative levels were similar (3.8 vs. 4.1, p = 0.182). Further, smokers showed higher 3 year-DFS rates than nonsmokers in group C (83.3% vs. 43.9%, p = 0.029). This suggests that while elevated postoperative CEA levels are associated with lower DFS rates in never and former smokers, they are not associated with lower DFS rates in current smokers. We conclude that persistent smoking alters the prognostic value of postoperative serum CEA levels in colorectal cancer patients and that, consequently, alternative surveillance strategies need to be developed for colon cancer patients with smoking habits.

Beyond the NCCN Risk Factors in Colon Cancer: An Evaluation in a Swedish Population-Based Cohort

BackgroundThe purpose of this study was to investigate whether pT3–4 and pN-subclassifications, lymph-node ratio (LNR), tumour deposits, pre- and postoperative carcinoembryonic antigen (CEA), and C-reactive protein (CRP)—all parameters commonly collected in clinical management—add information about recurrence risk against a background of routine clinicopathological parameters as defined by the NCCN.MethodsThe prospective cohort consisted of all 416 patients diagnosed with colon cancer stage I–III in Uppsala County between 2010 and 2015. Cox proportional hazard models were used to calculate hazard ratios for time to recurrence and overall survival. The results were compared with the entire Swedish population concerning parameters recorded in the national quality registry, SCRCR, during the same time period.ResultsThe Uppsala cohort was representative of the entire Swedish cohort. In unadjusted analyses, pT3-subclassification, pN-subclassification, LNR, tumour deposits, elevated postoperative CEA, and preoperative CRP correlated with recurrence. After adjusting for T-, N-stage, and NCCN risk factors, pN-subclassification, sidedness, and elevated postoperative CEA levels correlated with recurrence. Survival correlated with parameters associated with recurrence, LNR, and elevated postoperative CRP.ConclusionsAdditional information on recurrence risk is available from several routinely recorded parameters, but most of the risk is predicted by the commonly used clinicopathological parameters.

554P - Multicenter validation of the postoperative carcinoembryonic antigen combined prognostic model for stage III colon cancer

BackgroundThere are limitations in the prognosis stratification of stage III colon cancer patients using only the T and N stages, while other factors are unsure to be equally important. This study aimed to prove the prognostic importance of postoperative carcinoembryonic antigen (CEA) and stratify patients with stage III colon cancer more accurately by building a prognostic model combining CEA. MethodsThis was a retrospective cohort study. Patients with colon cancer who had CEA recorded within 100 days after resection at the centers from 2006 to 2017 were identified. The data included three different cancer centers in China: one training set and two validation sets, which were collected and analyzed in 2018. Postoperative CEA, T stage and N stage were combined to build the prognostic model, and patients with stage III colon cancer were divided into the high-risk group and the low-risk group. Harrell’s C-statistics, and net reclassification improvement (NRI) were used to assess the model performance. The disease-free survival (DFS) was compared between the high-risk group and the low-risk groups by the log-rank test. ResultsAmong patients with elevated postoperative CEA, we found that CEA tested within 20 days (early test group) after resection was not reliable, since DFS of the early test group was higher than that of the delayed test group (p=0.006). So, 834 patients with stage III disease which had CEA data for 21-100 days after resection were analyzed. In the training set, C-index for the model (combining T stage, N stage and postoperative CEA) was 0.74. Patients with elevated postoperative CEA, T4b, N2b or T4aN2a were classified as the high-risk group, with 3-year DFS of 55.8%, which was lower than the value of 86.0% in the low-risk group [hazard ratio (HR), 4.03; 95% CI, 2.49-6.54; p<0.001]. When compared to the TNM model, this new model achieved a 10% NRI. These results were confirmed in the validation sets. ConclusionsPatients with stage III colon cancer could be stratified much more accurately with the prognostic model combining T stage, N stage and postoperative CEA. Legal entity responsible for the studyThe authors. FundingHarbin Medical University Cancer Hospital Preeminence Youth Fund (JCQN2019-04). DisclosureAll authors have declared no conflicts of interest.

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.

The prognosis of gastric cancer patients with marginally elevated carcinoembryonic antigen (CEA) values after D2 radical gastrectomy

To investigate the clinical significance of the postoperative serum carcinoembryonic antigen (CEA) levels in gastric cancer patients who underwent D2 radical gastrectomy and to identify the prognostic factors for patients with marginally elevated postoperative CEA levels. We performed a retrospective study of 480 patients who were histologically diagnosed with gastric cancer and who underwent D2 radical surgery at the Sun Yat-sen University Cancer Center between January 2004 and December 2009. The follow-up lasted until June 2011. Chi-squared tests and Kaplan-Meier methods were employed to compare the adverse events and prognoses. In this group of gastric cancer patients, the postoperative serum CEA level (P = 0.002) was an independent prognostic factor; the same was true for the histological T and N staging (P < 0.001 and P = 0.045, respectively). In the group of marginally elevated postoperative CEA level gastric cancer patients, univariate analysis demonstrated that tumor position (P = 0.042); histological grade (P = 0.002); and Boarrmann type (P = 0.003) were significant prognostic factors. Multivariate analysis showed that the tumor position (P = 0.003) and histological grade (P = 0.007) were independent prognostic factors for these patients. Our study showed that patients with normal postoperative CEA levels have a better prognosis. Furthermore, for marginally elevated postoperative CEA level gastric cancer patients, the tumor position and histological grade were two important factors for predicting the prognosis and the need for aggressive therapy.

Carcinoembryonic antigen measurements in the management of esophageal cancer: An indicator of subclinical recurrence

Background: Detection of subclinical recurence after surgical resection of esophageal cancer would allow earlier treatment of recurrent disease and potentially offer a better outcome for rescue therapy. Methods: The utility of serum carcinoembryonic antigen (CEA) assay was evaluated in the management of patients with esophageal cancer. Results: Serum carcinoembryonic antigen was measured preoperatively in 74 patients. Elevation of the CEA level (>5 ng/mL) was present in 14 patients (19%). There was no relationship between preoperative CEA elevation and the stage of the tumor or the patients' survival. Eighty-three patients had CEA assay at regular follow-up intervals after resection. Objective evidence of recurrent disease was determined at similar intervals by chest radiography and abdominal and thoracic computed tomography scans. During follow-up, 53 of 83 patients developed recurrence. Postoperative elevation of CEA levels occurred in 32 patients, resulting in a sensitivity of 55% for detecting recurrent disease. Twenty-nine of the 32 patients who developed CEA elevation had objective evidence of metastatic disease. In 13 patients, the rise in CEA levels predated objective evidence of recurrence by a median of 4 months (range 3 to 35), and in 16 patients, it occurred concomitantly. The specificity with which an elevated postoperative CEA level indicated recurrence was high, 90%, with a positive predictive value of 91%. Conclusions: Postoperative CEA elevation is highly predictive of recurrent disease. In 16% of patients, elevation of CEA was the earliest objective sign of recurrence; such elevation should prompt consideration of adjuvant therapy.