Prognostic value of CEA and CA19-9 in patients with local advanced rectal cancer receiving neoadjuvant chemoradiotherapy, radical surgery and postoperative chemotherapy.

Background: We aim to investigate the prognostic factors and evaluate the role of carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) in local advanced rectal cancer (LARC) patients who received neoadjuvant chemoradiotherapy (neo-CRT), radical surgery and postoperative chemotherapy.

Methods: In total, 197 cases of LARC patients who underwent neo-CRT, total mesorectal excision (TME), and adjuvant chemotherapy were recruited. Serum levels of CEA and CA19-9 were detected both at baseline and after neo-chemoradiotherapy. Multivariate analysis was used to assess correlations between levels of CEA and CA19-9 and patients' prognosis (survival, recurrence, and metastasis). Rates of survival, distant metastasis (DM), and local recurrence (LR) were estimated using Kaplan-Meier survival analysis, the log-rank test, and Cox proportional hazards.

Results: The median follow-up time was 45.3 months, and a cohort of 197 patients was analyzed; 84 (42.6%) patients had elevated baseline CEA levels, 21 (10.7%) patients had elevated baseline CA19-9 levels, and 14 (7.1%) patients had both; 77.4% (65/84) patients with high CEA levels and 76.2% (16/21) with high CA19-9 levels returned to normal after neo-chemoradiotherapy. The Cox regression model suggested that elevated CEA was associated with an increased risk of disease-free survival (DFS) (HR: 2.058, 95% CI: 1.034-4.096, P=0.040) and DM (HR: 2.144, 95% CI: 1.058-4.346, P=0.034). Elevated CA19-9 was identified as an independent prognostic factor, with poorer overall survival (OS) (HR: 2.894, 95% CI: 1.196-7.006, P=0.018) and DFS (HR: 4.533, 95% CI: 2.067-9.940, P<0.001) and increased incidences of LR (HR: 6.139, 95% CI: 1.813-20.783, P=0.004) and DM (HR: 4.052, 95% CI: 1.892-8.678, P<0.001). Besides, combined CEA with CA19-9 was a stronger prognostic predictor. Patients with both high levels of CEA and CA19-9 had the poorest DFS (HR: 8.157, 95% CI: 3.232-20.591, P<0.001) and the highest risk of DM (HR: 8.790, 95% CI: 3.324-23.248, P<0.001).

Conclusions: LARC patients with high levels of CEA or/and CA19-9 at initial treatment have a worse prognosis, even after neo-CRT, subsequent radical resection, and adjuvant chemotherapy. These findings suggest that this subset of patients requires more intensive treatment or additional treatment strategies.