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Perioperative serum carcinoembryonic antigen: Powerful marker for prognostic prediction and adjuvant chemotherapy decision-making in patients with stage II and III colorectal cancer
Fen-Qi Du, Jia-Lu Liu, Liu-Dan Mai, Xin-Hao Han, Wen-Jie Song, Da Yang, Qiu-Ju Zhang, Rui Zhang, Yan-Long Liu, Jin-Xue Tong
Fen-Qi Du, Wen-Jie Song, Da Yang, Yan-Long Liu, Jin-Xue Tong, Department of Colorectal Surgery, Harbin Medical University Cancer Hospital, Harbin 150081, Heilongjiang Province, China
Jia-Lu Liu, Liu-Dan Mai, Xin-Hao Han, Qiu-Ju Zhang, Department of Biostatistics, Public Health School of Harbin Medical University, Harbin 150081, Heilongjiang Province, China
Qiu-Ju Zhang, Health Management Centre, Harbin Medical University Cancer Hospital, Harbin 150081, Heilongjiang Province, China
Rui Zhang, Department of Colorectal Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang 150040, Liaoning Province, China
Co-first authors: Fen-Qi Du and Jia-Lu Liu.
Co-corresponding authors: Yan-Long Liu and Jin-Xue Tong.
Author contributions: Tong JX and Liu YL conceptualized and designed the research; Du FQ, Liu YL, Zhang R, Song WJ and Yang D screened patients and acquired clinical data; Liu YL, Liu JL, Mai LD, Han XH and Zhang QJ performed data analysis; Du FQ, Tong JX and Liu YL wrote the paper. All the authors have read and approved the final manuscript. Tong JX and Liu YL proposed, designed and conducted serum carcinoembryonic antigen analysis and prepared the manuscript. Tong JX and Liu YL have played important and indispensable roles in the experimental design, data interpretation and manuscript preparation as the co-corresponding authors. Du FQ responsible for patient screening, enrollment, collection of clinical data, figure plotting, comprehensive literature search and manuscript preparation. Liu JL was instrumental and responsible for data analysis and interpretation, figure plotting and comprehensive literature search. Both Du FQ and Liu JL have made crucial and indispensable contributions towards the completion of the project and thus qualified as the co-first authors of the paper.
Supported by Heilongjiang Provincial Natural Science Foundation of China, No. PL2024H173; and Nn10 Project of Harbin Medical University Cancer Hospital, No. 04000079.
Institutional review board statement: The study was approved by the Ethics Committee of Harbin Medical University (No. HMUIRB2024014) on 22 October 2024 and the Liaoning Cancer Hospital and Institute (No. 2019G0209) on 25 February 2019.
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: The authors have no relevant financial or non-financial interests to disclose.
Data sharing statement: The datasets used and/or analyzed during the current study available from the corresponding author on reasonable request.
Corresponding author: Jin-Xue Tong, Professor, Department of Colorectal Surgery, Harbin Medical University Cancer Hospital, No. 150 Haping Road, Nangang District, Harbin 150081, Heilongjiang Province, China.
601705@hrbmu.edu.cn
Received: September 22, 2025
Revised: November 26, 2025
Accepted: January 12, 2026
Published online: March 7, 2026
Processing time: 167 Days and 4.9 Hours
BACKGROUND
Assessment of the prognosis, follow-up monitoring, and adjuvant treatment decision-making for patients with stage II and III colorectal cancer (CRC) are controversial, as CRC harbors tremendous heterogeneity. Carcinoembryonic antigen (CEA) is an important tumor marker; however, the use of this marker in the management of CRC has not garnered adequate attention.
AIM
To determine the significance of perioperative CEA levels in prognostic stratification and treatment decision making to provide personalized diagnosis and treatment for patients with stage II and III CRC.
METHODS
Patients in the training and validation cohorts were diagnosed with primary stage II or III CRC. Preoperative CEA (pre-CEA) and postoperative CEA (post-CEA) were collectively defined as perioperative CEA. Kaplan-Meier (K-M) survival analyses were used to describe patient survival. Cox stepwise regression analysis based on Akaike information criterion was used to determine the prognostic value of clinicopathological characteristics. Nomograms were developed to predict the probability of overall survival (OS) and disease-free survival (DFS). Annual hazard curves and pie charts were used to demonstrate the features of recurrence or metastasis. Differences were considered statistically significant at P < 0.05.
RESULTS
A total of 2496 and 1293 patients were included in the training and validation cohorts, respectively. K-M analysis indicated that patients with elevated perioperative CEA had poorer OS and DFS, with post-CEA being an independent prognostic factor for OS and DFS. Nomograms based on factors associated with prognosis were constructed, which showed good predictive ability for 3-, 5-, and 7-year OS and DFS. Patients with elevated perioperative CEA were more likely to have recurrence or metastasis, and the period of the second year after surgery was the peak time of recurrence or metastasis. OS and DFS were significantly worse in patients without adjuvant chemotherapy when they had elevated perioperative CEA. Adjuvant chemotherapy could significantly improve the OS of patients with elevated perioperative CEA. Patients with elevated post-CEA who received XELOX could achieve better OS and DFS.
CONCLUSION
Perioperative CEA demonstrate sufficient sensitivity in the prognosis prediction and follow-up of patients with stage II and III CRC. Furthermore, perioperative CEA, especially post-CEA, show promise in guiding adjuvant chemotherapy, suggesting potential for further study.
Core Tip: Perioperative carcinoembryonic antigen (CEA) is an important prognostic predictor and stratification marker, and it is reasonable to apply perioperative CEA to guide postoperative follow-up of stage II and III colorectal cancer (CRC) patients. The nomogram model based on perioperative CEA can well predict the 3-year, 5-year, and 7-year overall survival and disease-free survival of stage II and III CRC patients. Perioperative CEA can be used to assess recurrence or metastasis features of stage II and III CRC patients. Perioperative CEA, especially postoperative CEA, has the potential to guide adjuvant chemotherapy in stage II and III CRC patients, which is worthy of further study.
