Prognostic Relevance of Preoperative "Tumor Marker Index" Values in Patients with Stage III Rectal Adenocarcinoma

Background: Colorectal cancer (CRC) is the third most common malignancy and the second leading cause of cancer-related deaths worldwide. Studies often consider colon and rectal cancers together. The combination of CA 19-9 and CEA markers is used to improve diagnostic accuracy, but there are no reports on the use of this combination as a prognostic predictor for CRC. The study by Kamada et al. was the first to use the "tumor marker index" (TMI), the geometric mean of normalized CEA and CA 19-9 in CRC, demonstrating the prognostic capabilities of this novel marker. However, it is not known how the preoperative value of TMI compares and fits into the current system of prognostic factors for preoperative prediction of overall survival (OS) and disease-free survival (DFS). Objective: The aim was to investigate the significance of preoperatively determined TMI in predicting three-year overall survival (3Y-OS) and three-year disease-free survival (3Y-DFS) in patients with stage III adenocarcinoma of the upper and middle rectum. Methods: Our retrospective cohort study included 93 patients who underwent open anterior resection of the rectum between January 2015 and December 2020. Optimal cut-off values of the markers were determined by ROC analysis. Statistical analysis was performed using IBM SPSS Statistics 22 and R 4.4.0. Results: Patients with TMI ≥1.0158 had a statistically significantly higher likelihood of mortality within three years (p=0.012). Patients with TMI ≥0.979 had a statistically significantly higher likelihood of disease-free survival of less than three years (p=0.003). Compared to CEA and CA 19-9, TMI had the highest AUC for predicting 3Y-OS (0.740, p=0.020) and 3Y-DFS (0.780, p=0.012). Adding TMI to other predictors increased the AUC for predicting both 3Y-OS (from 0.748 to 0.853) (p=0.001) and 3Y-DFS (from 0.711 to 0.850) (p=0.001). Conclusion: Our study confirmed previous findings on the usefulness of preoperative TMI as a prognostic marker, further expanding knowledge about its accuracy by comparing and combining it with established prognostic factors, including CEA and CA 19-9.