The Relationship Between Carcinoembryonic Antigen and Prognosis in Colorectal Cancer

Dear Editor,I have read the article by Aydın et al. titled "The Relationship Between Carcinoembryonic Antigen and Prognosis in Colorectal Cancer". The authors report improved prognosis among patients with colon cancer who have high preoperative carcinoembryonic antigen (CEA) levels. Higher CEA levels are achieved with increased lymphovascular, venous, and perineural invasion, providing valuable information about the biological aggressiveness of colorectal cancer.However, I would like to draw attention to a few methodological issues that deserve further discussion.First, the study includes only compartments with high preoperative CEA levels (≥3 ng/mL) and excludes those with normal CEA levels. In conclusion, the study to continue the reference distribution is to assess the true prognostic evaluation of high CEA. Previous studies have shown that data with normal preoperative CEA ratios indicate progressively better survival outcomes for those with higher levels (1,2), and excluding these references reveals the prognostic value of different CEA ratios. Indeed, even among variables with CEA levels within the normal range, those with higher levels appear to have worse overall survival; this suggests that the effect of CEA on prognosis is a continuum rather than a single equation (2).Secondly, there is a marked disparity in width between the three study groups (168 vs 18 vs 39 patients). This disparity is due to the fact that the power of the ratios with high CEA is significantly reduced, and the type II error rate increases. This disparity can be explained by the fact that, although those with very high CEA levels have a shorter survival, no significant difference is observed in overall survival. Third, although similarities have been reported among groups within the problem universe, the authors performed only univariate analyses. Since survival in colorectal cancer is affected by numerous clinicopathological variables, including TNM stage, lymphovascular invasion, perineural invasion, tumor differentiation, and metastatic disease, they performed multivariate blast analysis to determine whether preoperative CEA independently predicts survival. Numerous large-scale studies have shown that preoperative CEA is an independent prognostic factor only after adjustment for these variables (3,4). Furthermore, perioperative CEA dynamics provide additional prognostic information beyond a single preoperative view, including postoperative normalization and prolonged course (5,6).Another observation was that cardiac metastasis was significantly more common at the lowest CEA levels; it was not observed in the higher-CEA groups. This finding appears to be logically consistent with the literature data, which generally associates increasing CEA distributions with metastatic burden [4,7]. Given the small number of patients in the second and third groups, it is possible that this result reflects monitoring of density performance in a real biological phenomenon and warrants further explanation.Finally, the study pooled treated temperatures over a one-year period (2012-2022). During this time, significant advancements occurred in colorectal cancer surgery, perioperative recovery, pathological staging, and follow-up protocols. These temporal changes may have affected survival outcomes and recurrence. Grouping by treatment duration or subgroup analyses by treatment characteristics would strengthen the conclusions. Despite these limitations, the study suggests a holistic deterioration, in which a relationship between negative problematic characteristics and preoperatively high CEA levels may lead to further ongoing improvements. To better understand the independent prognostic role of preoperative CEA in colorectal cancer, a prospective, multicenter study is planned for the future, including units with both normal and high CEA rankings, and incorporating multivariate survival analyses. I thank the authors for their valuable contributions and hope that these comments will encourage further discussion regarding the optimal use of CEA as a prognostic biomarker in colorectal cancer.