Novelty in Colorectal Cancer Biomarkers: The Predictive Value and Clinical Utility of the Carcinoembryonic Antigen and Aldehyde Dehydrogenase 1B1 Autoantibodies for Assessing Tumour Biology and the Cancer Stem Cell Burden

T1370 Elevated Cyst Fluid Carcinoembryonic Antigen (CEA) Level is Not a Accurate Predictive Marker of Invasive Cancer in Patients With Intraductal Papillary Mucinous Neoplasm (IPMN) of the Pancreas

Carcinoembryonic antigen (CEA) has limited value as an isolated predictor for survival among colorectal cancer (CRC) patients. D-dimer (DD) is a strong predictor of survival among metastatic CRC patients, but the prognostic value in non-metastatic CRC patients remains controversial. We examined the prognostic value of preoperative DD levels in relation to CEA levels in non-metastatic, resectable CRC patients. Between October 2003 and November 2005, 166 patients were included. We used the Kaplan-Meier method to compute 5-year mortality rates, stratified by preoperative DD and CEA levels. Adjusted Cox regression analysis was used to compute mortality rate ratios (MRRs) during postoperative years 0-1 and 1-5 based on the preoperative CEA and DD levels. The cumulative 5-year mortality rate was 15 % (95 % confidence interval [CI], 9-25 %) in patients with normal DD and CEA levels, 30 % (CI, 16-53 %) in patients with isolated elevated CEA levels, 37 % (CI, 25-53 %) in patients with isolated elevated DD levels, and 60 % (CI, 37-83 %) in patients with elevated CEA and DD levels. Elevated CEA was associated with an approximately ten-fold increase in mortality within the first postoperative year (adjusted MRR 9.8, CI 2.5-38.3); this association was lost during postoperative years 1-5 (adjusted MRR 1.1, CI 0.5-2.7). Elevated DD was associated with a greater than two-fold increase in mortality during postoperative years 0-1 (adjusted MRR 2.8, CI 0.7-11.0) and 1-5 (adjusted MRR 2.2, CI 1.1-4.8). DD is a strong predictor of survival among non-metastatic curatively resected CRC patients, particularly in combination with CEA.

Background: Globally, colorectal malignancy is the 3rd most frequent cancer and the 2nd major cause of mortality. Serum carcinoembryonic antigen (CEA) is a simple tumor marker for the diagnosis, predicting response to therapy and survival and identifying the recurrence of colorectal cancer. Therefore, the aim was to evaluate the pattern of serum CEA levels in patients with colorectal cancer presenting at a tertiary care hospital in Karachi Patients and methods: It was a cross-sectional study conducted at the Department of Medical Oncology of Jinnah Postgraduate Medical Center, Karachi from January till August 2019. One ninety-nine patients of 12-80 years age and either gender diagnosed with colorectal cancer (biopsy-proven) were included. Data on demographics, clinical and pathological findings were recorded in the pre-designed proforma. The serum CEA levels in colorectal cancer patients were assessed using an ELISA kit. CEA levels higher than 5.0 ng/mL were deemed as elevated CEA levels in colorectal patients. Data were analyzed using SPSS version 23. Results: A total of 191 colorectal cancer patients were included. The mean age of the patients was 42.81±15.22 years. Most of the patients (61.3%) were male. Out of 191 colorectal cancer patients, 60 (31.4%) had CEA level 0-0.3 ng/ml, whereas 79 (41.4%) had elevated serum CEA level (>10 ng/ml). The CEA levels were stratified with respect to effect modifiers. The size of the tumor, TNM staging and localization and metastasis of cancer showed a statistically significant difference between levels of CEA (p<0.05). Conclusion: The raised CEA levels are associated with clinically progressive or presence of residual and recurrent disease. For patients with progressive tumors, particularly colorectal carcinoma, CEA assays are an important guide to assess the burden of the tumor, hence clinicians and surgeons ought to monitor antigen levels. It is recommended to enhance the clinical efficacy of the CEA levels.

No benefit of more intense follow-up after surgery for colorectal cancer in the risk group with elevated CEA levels – An analysis within the COLOFOL randomized clinical trial

Invited commentary

PurposeElevated levels of serum carcinoembryonic antigen (CEA) following a curative resection of colorectal cancer (CRC) indicate recurrence; however, the levels of CEA may be elevated above the normal limit without recurrence. The aim of this study is to analyze the diagnostic accuracy of elevated serum CEA for predicting recurrence in postoperative stage II and stage III CRC patients.MethodsA total of 336 stage II and stage III CRC patients who underwent a curative resection between January 2005 and October 2009 were enrolled. Sensitivities, specificities, positive predictive values (PPVs), negative predictive values (NPVs), likelihood ratios and post-test probabilities of recurrence associated with elevated CEA were analyzed and compared.ResultsThe median follow-up duration was 45 months (36 to 134 months). Twenty-seven of 189 stage II patients (14.3%) and 52 of 147 stage III patients (35.4%) developed recurrence during the follow-up period. Sensitivities, specificities, PPVs, and NPVs of elevated CEA were 37.0%, 91.4%, 41.7%, and 89.7%, respectively, in stage II patients and 46.2%, 90.5%, 72.7%, and 75.4% in stage III patients. Post-test probabilities of recurrence associated with elevated CEA were 41.8% in stage II patients and 71.9% in stage III patients.ConclusionThe predictive performance of the probability of recurrence associated with elevated serum CEA after a curative resection in stage II CRC patients is lower than that in stage III CRC patients.

Background: For different cancers, different tumor markers are overexpressed. Carcinoembryonic antigen (CEA) levels are raised commonly in adenocarcinoma of colon, breast, and lung. About 80% of primary colorectal cancers (CRCs) show high serum CEA levels. Hence, CEA levels can be used as a prognostic factor - for both metastasis and recurrence - with persistent high levels. Currently, the American Society of Clinical Oncology recommends CEA as tumor marker and prognostic indicator in CRC patients. Aim and Objectives: The aim of the study was to determine the high level of CEA in CRCs and to study the level of CEA in cases of metastases and recurrence and to determine the sensitivity of CEA value in prognosis of CRCs. Materials and Methods: It was a prospective observational study. All the patients more than 20 years of age and of both sexes were included in this study who were diagnosed with primary localized CRC, metastatic CRC, or recurrent disease. The study was performed in the Department of General Surgery, R. G. Kar Medical College and Hospital between January 2020 and August 2021. Results: Total cases were classified according to Duke staging - 10% in Group A, 19% in Group B, 38% in Group C, and 33% in Group D. In Group A and B, about 35% of patients had increased CEA levels, whereas in Group C and D, more than 90% of patients had increased CEA levels with significant P < 0.05. Overall 80% of the patients had elevated CEA levels, so remaining 20% had normal values. In cases of recurrent colorectal carcinoma, >90% of patients had raised CEA levels, and in metastatic disease cases, CEA level was significantly raised in 82% of patients. Conclusion: In case of colorectal CA, preoperative raised serum CEA level is associated with poor prognosis, as chance of recurrence increased. Along with that increased CEA level is also associated with increased chance of metastatic disease. Hence, serial monitoring of serum CEA level in postoperative period may help to detect any recurrence early, thus reducing chance of mortality and morbidity.

De novo neuroendocrine prostate cancer (NEPC) is a rare subtype of prostate cancer (PCa) and few markers are available for screening and monitoring. Potential circulating or fluid markers might facilitate early diagnosis thus improving prognosis of NEPC, especially for de novo NEPC. A man of 71-year was presented with elevated level of serum carcinoembryonic antigen (CEA) (1296.5 ng/ml) and normal PSA (0.47ng/ml). Gastrointestinal endoscopy showed no signs of gastric or colorectal cancer. Fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET-CT) and prostate-specific membrane antigen PET-CT (PSMA PET-CT) indicated prostate cancer with metastases including pelvic lymph nodes, bone as well as lung metastases. Biopsy of prostate revealed mixed carcinoma including small cell neuroendocrine carcinoma (SCNEC) and adenocarcinoma (Gleason score of 4 + 5). Immunohistochemistry (IHC) staining and next generation sequencing demonstrated a strong expression of chromogranin A (CgA), synaptophysin (SYN) and CEA, and a germline mutation in BRCA2, respectively. After a prostatic massage, an increased level of CEA (137 ng/ml vs 5 ng/ml) was detected in urine. Olaparib, a Poly ADP-ribose polymerase inhibitor (PARPi), combined with androgen deprivation therapy (ADT) were administrated. FDG PET-CT indicated tumor regression in both quantity and size three months later, and CEA levels of serum and urine decreased to 23 ng/ml and 2.4 ng/ml 4 months later, respectively. This is the first report of a de novo NEPC presented with an elevated level of CEA, in which CEA was also detected in urine specimen post a prostatic massage. After a combination treatment of ADT for 3 months, levels of CEA in both serum and urine decreased sharply when tumor regressed radiologically. CEA might be a marker of screening and monitoring of NEPC.

Carcinoembryonic antigen (CEA) has been thought to be a diagnostic and prognostic indicator of colorectal cancer. Initial descriptions of CEA as a tumor specific antigen suggests a relationship between tumor CEA and circulating plasma CEA. To define the relationship between CEA and colorectal carcinoma, we have studied the CEA concentration of preoperative plasma, tumor tissue, and normal bowel distant from tumor in 35 patients who had clinically curative resections. Tumor histology was evaluated for Dukes class, histologic grade, necrosis, and vessel invasion. Regression analysis yielded no evidence of correlation between tumor CEA and plasma CEA. No correlation could be shown between tumor concentration of CEA and the histological parameters previously noted. CEA was found in all specimens of normal bowel. Furthermore, in 34% of the cases studied, the tumor CEA was not significantly higher than in normal bowel. No significant difference was shown when histopathological findings were compared to normal and abnormal plasma CEA values. These findings suggest the following conclusions: CEA is not tumor specific. Increased levels of CEA in tumor tissue are not a constant finding in colorectal carcinoma. Tumor levels of CEA do not appear to correlate with histologic degree of tumor differentiation. Elevated plasma levels of CEA do not necessarily connote elevated tumor tissue levels of CEA, and conversely, normal plasma levels of CEA do not necessarily mean low levels of tumor CEA.

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.

The objective of the current study was to look at the levels of blood micro ribonucleic acid- (miR-) 497, carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 24-2, and hepatitis B surface antigen (HBsAg) in patients with colorectal cancer (CRC), as well as the clinical importance of these markers in CRC patients. The serum levels of miR-497, CEA, CA24-2, and HBsAg were compared between 60 patients with CRC (observation group) and another 60 patients with colorectal polyps (control group). The 4 indicators in patients with lymph node metastasis and liver metastasis were compared. The diagnostic effects of 4 detection methods and the combined detection were analyzed, and the influence of 4 indicators on the 5-year cumulative survival rate of patients was discussed. The results showed that the serum levels of miR-497 and HBsAg were lower, and the levels of CEA and CA24-2 were higher in the observation group (P < 0.05). The combined detection had the best diagnostic effect, and CEA alone had the best prediction effect. The serum level of miR-497 was significantly lower in patients with lymphatic metastasis, with the significantly higher levels of CEA and CA24-2 (P < 0.05). The HBsAg level of patients with liver metastases was greatly lower than that of patients without liver metastases (P < 0.05). The 5-year cumulative survival rate of patients with high levels of CEA and CA24-2 was significantly lower than that of patients with low level of CEA. The 5-year cumulative survival rate was lower in patients with low level of HBsAg, but the difference was small. The 5-year cumulative survival rate of patients with elevated serum miR-497 was observably lower. In conclusion, combined detection could diagnose CRC more accurately. Serum miR-497, CEA, and CA24-2 were important in the diagnosis of lymph node metastasis of CRC. HBsAg did a better job of predicting liver metastases in CRC patients. High level of CEA significantly reduced the cumulative survival rate of CRC patients and could predict the long-term survival rate of patients. Serum levels of miR-497, CEA, CA24-2, and HBsAg played a positive role in the diagnosis and evaluation of CRC and could identify lymph node and liver metastases, having a high clinical guidance value.

Tumor markers such as carcinoembryonic antigen (CEA) and cancer antigen 15-3 (CA15-3) are widely used for monitoring breast cancer. However, the prognostic efficacy of preoperative elevations of CEA and CA15-3 levels in breast cancer patients remains controversial. We retrospectively analyzed the clinicopathological parameters of 149,238 patients in the Korean Breast Cancer Society Registry Database who underwent surgery between January 2000 and December 2015. The patients with elevated CA15-3/CEA levels had worse overall survival (OS) than the patients with normal CA15-3/CEA levels. For the luminal A subtype, the CA15-3- and CEA-elevated group had a hazard ratio (HR) of 2.14 (95% CI 1.01-4.55). The CA15-3-elevated group had an HR of 2.38 (95% CI 1.58-3.58) and the CEA-elevated group had an HR of 1.79 (95% CI 1.20-2.68) compared to the normal group. For the luminal B subtype, the CA15-3- and CEA-elevated group had an HR of 3.99 (95% CI 2.23-7.16), whereas the CA15-3-elevated group had an HR of 2.38 (95% CI 1.58-3.58) and the CEA-elevated group had an HR of 1.79 (95% CI 1.20-2.68). For the HER2 subtype, elevated CEA level was the only independent prognostic factor. However, for the triple-negative breast cancer (TNBC) subtype, elevated preoperative CEA and CA15-3 levels were not significant prognostic factors for OS. Preoperative CEA and CA15-3 levels showed varying prognostic ability according to breast cancer subtype. Preoperative CA15-3 and CEA elevation are significant prognostic factors for luminal breast cancer, but they were not significant factors for TNBC.

To determine whether serum levels of carcinoembryonic antigen (CEA) correlate with the presence of primary colorectal cancer (CRC), and/or recurrent CRC following radical resection. A total of 413 patients with CRC underwent radical surgery between January 1998 and December 2002 in our department and were enrolled in this study. The median follow-up period was 69 mo (range, 3-118 mo), and CRC recurrence was experienced by 90/413 (21.8%) patients. Serum levels of CEA were assayed preoperatively, and using a cutoff value of 5 ng/mL, patients were divided into two groups, those with normal serum CEA levels (e.g., ≤ 5 ng/mL) and those with elevated CEA levels (> 5 ng/mL). The overall sensitivity of CEA for the detection of primary CRC was 37.0%. The sensitivity of CEA according to stage, was 21.4%, 38.9%, and 41.7% for stages I-III, respectively. Moreover, for stage II and stage III cases, the 5-year disease-free survival rates were reduced for patients with elevated preoperative serum CEA levels (P < 0.05). The overall sensitivity of CEA for detecting recurrent CRC was 54.4%, and sensitivity rates of 36.6%, 66.7%, and 75.0% were associated with cases of local recurrence, single metastasis, and multiple metastases, respectively. In patients with normal serum levels of CEA preoperatively, the sensitivity of CEA for detecting recurrence was reduced compared with patients having a history of elevated CEA prior to radical resection (32.6% vs 77.3%, respectively, P < 0.05). CRC patients with normal serum CEA levels prior to resection maintained these levels during CRC recurrence, especially in cases of local recurrence vs cases of metastasis.

P-0213 Surveillance With Serial Serum Carcinoembryonic Levels Detect Colorectal Cancer Recurrences in Patients Who are Initial Nonsecretors

Survival benefit of adjuvant chemotherapy (ACT) remained controversial in patients with stage II/III rectal cancer (RC) who received neoadjuvant therapy and surgery. This study aimed to investigate the guiding role of elevated pretreatment serum carcinoembryonic antigen (CEA) levels for receiving ACT in yield pathological Tis-3N0 (ypTis-3N0) RC patients after neoadjuvant radiotherapy and surgery. Between 2004 and 2015, 10,973 RC patients with ypTis-3N0 who received neoadjuvant radiotherapy and radical surgery were retrospectively analyzed using the Surveillance, Epidemiology, and End Results (SEER) database. Compared with CEA-normal group, elevated-CEA patients had worse 5-year CSS rate (90.1 vs 83.5%). The 5-year CSS rates were 86.3 and 87.4% for ypTis-3N0M0 patients with or without ACT, respectively. Patients receiving ACT had a comparable 5-year CSS rate compared to those who did not regardless of CEA levels in ypTis-3N0M0 RC patients (CEA elevation group: 76.4 vs. 83.5%, P = 0.305; CEA normal group: 90.0 vs. 90.1%, P = 0.943). Intriguingly, ypT3N0M0 RC patients with elevated CEA levels may benefit from ACT (5-year CSS: 69.1 vs. 82.9%, P = 0.045), while those with normal CEA levels did not (5-year CSS: 89.3 vs. 89.3%, P = 0.885). Multivariate Cox analysis demonstrated that ACT tended to be a protective factor in elevated-CEA ypT3N0M0 RC patients (HR = 0.633, 95% CI = 0.344–1.164, P = 0.141), while ACT was not associated with improved CSS in normal-CEA ypT3N0M0 RC patients (HR = 1.035, 95% CI = 0.487–2.202, P = 0.928). Elevated pretreatment serum CEA levels may serve as a promising biomarker guiding ACT in rectal cancer patients with ypT3N0M0.