Prognostic value of changes in serum carcinoembryonic antigen levels for preoperative chemoradiotherapy response in locally advanced rectal cancer

Abstract

Background: Preoperative chemoradiotherapy (CRT) is a standard treatment modality for locally advanced rectal cancer. However, CRT alone cannot improve overall survival. Approximately 20% of patients with CRT-resistant tumors show disease progression. Therefore, predictive factors for treatment response are needed to identify patients who will benefit from CRT. We theorized that the prognosis may vary if patients are classified according to pre- to post-CRT changes in carcinoembryonic antigen (CEA) levels.

Aim: To identify patients with locally advanced rectal cancer for preoperative chemoradiotherapy based on carcinoembryonic antigen levels.

Methods: We retrospectively included locally advanced rectal cancer patients who underwent preoperative CRT and curative resection between 2011 and 2017. Patients were assigned to groups A, B, and C based on pre- and post-CRT serum CEA levels: Both > 5; pre > 5 and post ≤ 5; and both ≤ 5 ng/mL, respectively. We compared the response to CRT based on changes in serum CEA levels. Receiver operating characteristic curve analysis was performed to determine optimal cutoff for neutrophil-lymphocyte ratio and platelet-lymphocyte ratio. Multivariate logistic regression analysis was used to evaluate the prognostic factors for pathologic complete response (pCR)/good response.

Results: The cohort comprised 145 patients; of them, 27, 43, and 65 belonged to groups A, B, and C, respectively, according to changes in serum CEA levels before and after CRT. Pre- (P < 0.001) and post-CRT (P < 0.001) CEA levels and the ratio of down-staging (P = 0.013) were higher in Groups B and C than in Group A. The ratio of pathologic tumor regression grade 0/1 significantly differed among the groups (P = 0.003). Group C had the highest number of patients showing pCR (P < 0.001). Most patients with pCR showed pre- and post-CRT CEA levels < 5 ng/mL (P < 0.001, P = 0.008). Pre- and post-CRT CEA levels were important risk factors for pCR (OR = 18.71; 95%CI: 4.62-129.51, P < 0.001) and good response (OR = 5.07; 95%CI: 1.92-14.83, P = 0.002), respectively. Pre-CRT neutrophil-lymphocyte ratio and post-CRT T ≥ 3 stage were also prognostic factors for pCR or good response.

Conclusion: Pre- and post-CRT CEA levels, as well as change in CEA levels, were prognostic markers for treatment response to CRT and may facilitate treatment individualization for rectal cancer.

Keywords: Carcinoembryonic antigen levels; Change in serum carcinoembryonic antigen; Neoadjuvant chemoradiation therapy; Prognostic factor; Rectal cancer; Response of chemoradiotherapy.

Figure 1

Survival in study groups according to pre- and post-chemoradiotherapy serum levels of carcinoembryonic antigen. A: Five-year disease-free survival in the groups according to pre- and post-chemoradiotherapy (CRT) serum carcinoembryonic antigen (CEA) levels (Group A vs Group B vs Group C; P = 0.145); and B: Five-year overall survival in the groups according to pre- and post-CRT serum CEA levels (Group A vs Group B vs Group C; P = 0.005). Group A: patients with pre- and post-CRT CEA levels > 5 ng/mL; Group B: Patients with pre- and post-CRT CEA levels > 5 and ≤ 5 ng/mL, respectively; and Group C: Patients with pre- and post-CRT CEA levels < 5 ng/mL.