Ethics approval and consent to participate
The local ethics committee of the Yunnan Cancer Hospital, Xishan Region, Kunming, People’s Republic of China, approved this retrospective study (No. KY201824), which complied with the Declaration of Helsinki and good clinical practice guidelines. The requirement for informed consent was waived by the committee owing to the study’s retrospective nature. All the patient data in the survey were anonymized.
Study Design and Patient Cohort
We retrospectively enrolled 761 stage II-III colon cancer patients who underwent direct surgical resection between April 2008 and February 2019 at Yunnan Cancer Hospital or the Sixth Affiliated Hospital of Sun Yat-Sen University, China. The study flow chart, and detailed inclusion and exclusion criteria are shown in Figure 1.
Extract the CEA value closest to the operation time from the electronic medical record. The preoperative CEA was defined as the CEA value closest to the operation time, and the postoperative CEA was defined as the final CEA value within 12 weeks after the operation and before starting adjuvant chemotherapy. At the same time, collect demographic, clinical, and pathological data of patients (6). All CEA measurements in Yunnan Cancer Hospital were performed with COBAS 800 e602 immunoassay analyzer (Roche Diagnostics, Tokyo, Japan) with a chemiluminescence immunoassay analyzer. Sun Yat-sen University uses the Alinity I immunoassay analyzer (Abbott Diagnostics, Chicago, USA), following the World Health Organization standard method (code 73/601) (12). The reference range of serum CEA is between 0.0 and 5.0 ng/mL. A value higher than 5.0 ng/mL is considered an increase in CEA, and a value lower than 5.0 ng/mL is considered normal (2,6).
Exposures
Patients were grouped into 3 cohorts: normal postoperative CEA without tumor deposits(TD), normal postoperative CEA with TD, and elevated postoperative CEA.
Adjuvant Chemotherapy Protocol
According to NCCN clinical practice guidelines in colon cancer, some patients with stage II-III colon cancer received postoperative adjuvant chemotherapy (2). Adjuvant chemotherapy regimens include FOLFOX, CapeOX, single-agent capecitabine, or 5-FU/leucovorin (5).
Surveillance protocol
The patient's clinical evaluation includes serum CEA test level, physical examination, imaging examination (CT/MRI), and colonoscopy biopsy. The CEA level is measured every 3 to 6 months for 3 years. Perform imaging examinations at least every 12 months and at least 3 years, including plain scans of the patient’s chest, abdomen, and pelvis and contrast enhancement. Colonoscopy is performed once a year after the operation, at intervals of every three years. Colonoscopy, histopathological examination, or imaging examination confirmed all cases of recurrence and metastasis.
Outcomes
This study combines postoperative CEA levels to predict and evaluate the likelihood and value of recurrence in colon cancer patients undergoing radical surgery. It is worth noting that the recurrence-free survival time refers to the duration between surgery and recurrence, metastasis and death of the patient. If the patient cannot be followed up, the recurrence-free survival time will be calculated based on the last follow-up date. Each enrolled patient underwent a 3-year full follow-up, and patients less than 3 years were not included in this study.
Statistical analysis
Use χ2 or Fisher's exact test (discrete variables) and unpaired t-test, Wilcoxon signed-rank test, or continuous variable analysis of variance to compare patient characteristics. Kaplan-Meier method and log-rank test were used for survival analysis. All P values below 0.05 are statistically significant. Cox proportional hazards regression model was used to evaluate factors independently related to RFS. According to the clinical relevance and statistical significance of the univariate analysis, the variables included in the final multivariate model were selected (cutoff value, P = 0.10). Factors related to disease control are tested through logistic regression in single factor and multivariate analysis. The alpha level is 5%. The internal validation of the final multivariate model of RFS was carried out on the population with an overall recurrence risk score through the bootstrap sample program (n = 1000 samples). Use SPSS23.0 software and GraphPad-prism 8 drawing software for statistical analysis (13).