The prognostic role of circulating CA19-9 and CEA in patients with colorectal cancer

Background: Carcinoembryonic antigen (CEA) is the only prognostic circulating biomarker used in clinical practice for recurrence free (RFS), progression free (PFS) and overall survival (OS) in patients with colorectal cancer (CRC). Not all CRC tumors express this protein and carbohydrate antigen (CA)19-9 has been proposed as an adjunctive in prognostication. We aimed to test if CA19-9 yielded additional information to CEA regarding prognosis. Patients and methods: We included 886 patients with CRC across eight clinical cohorts. Preoperative serum samples were collected from 376 patients with stage I-III CRC and from 510 with metastatic (m)CRC before 1st (n = 233), 3rd (n = 178) and 3rd/4th (n = 99) line chemotherapy. CA19-9 and CEA were determined by routine assays, the values were log-2 transformed and entered as variables in Cox regression models with RFS (stage IIII), PFS and OS as the outcomes, adjusted for age, sex, and site of primary tumor and mutual adjustment between CA199 and CEA. Random effects meta-analyses were conducted for stage I-III,1st line, and 3rd/4th line mCRC cohorts separately. Results: Meta-analyses showed that higher pre-treatment CA19-9 and CEA were associated with shorter RFS (CA19-9: hazard ratio per doubling of concentration (HR)=1.20, 95 % confidence interval (CI) 1.05-1.38; CEA: HR=1.22, 95 % CI 1.05-1.41) in stage I-III CRC. Only higher CEA was associated with shorter OS in 1st line mCRC (HR=1.07, 95 % CI 1.00-1.07). Conclusion: CA19-9 might aid in identifying patients with a high risk of recurrence after primary radical resection. Further studies are needed to validate these findings.