Elevated CA19-9 within the normal range suggests poorer prognosis in stage II CRC: A retrospective analysis of a large sample in a single center.

Objective: Carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA) serve as pivotal tumor markers in colorectal cancer (CRC). However, uncertainty persists regarding the prognostic significance of the two tumor markers when falling within the normal range. We attempt to compare the prognostic differences of tumor markers at different levels within the reference range.

Methods: This retrospective study scrutinized 2,167 cases of stage II CRC verified by pathology after surgery at the Fudan University Shanghai Cancer Center. Using R software to calculate the optimal critical value to compare the clinical and pathological characteristics and prognosis of different levels of tumor markers. The survival and regression modeling strategies packages of R software drew the nomograms.

Results: Utilizing R software, the optimal critical value of CA19-9 was determined as 12.12 U/mL and that of CEA as 1.89 U/mL. Kaplan-Meier survival analysis unveiled that, within the normal range, higher levels of CEA were linked to poorer overall survival (OS) [HR = 1.829 (1.280, 2.989), P = 0.0033] and disease-free survival (DFS) [HR = 1.472 (1.114, 1.944), P = 0.0444]. Similarly, heightened levels of CA19-9 also indicated inferior OS [HR = 1.750 (1.203, 2.455), P = 0.0076] and DFS [HR = 1.361 (1.098, 1.686), P = 0.0049]. Furthermore, multivariate analysis identified CA19-9 as an independent risk factor for OS (HR = 1.49,95% CI: 1.086-2.045, P = 0.014) and DFS (HR = 1.327,95% CI: 1.070-1.647, P = 0.01), while the impact of CEA on OS and DFS was not statistically significant. A nomogram constructed based on the Cox regression model can effectively evaluate the prognosis of CRC patients.

Conclusion: Although within the normal range, elevated CA19-9 was associated with an inferior prognosis, chemotherapy decisions of different intensities can be adjusted based on nomograms. This work will contribute to standardizing the diagnosis and treatment of stage II CRC and provide clinicians with essential insights for chemotherapy decisions.