The prognostic value of the combination of post-operative CEA and CA199 for LARC patients undergoing NCRT was tested in this study. Patients with post-operative CEA < 2.550 had better OS and DFS, while post-operative CA199 < 16.36 only had better OS. The results of multivariate analysis showed that CSTB score was an independent factor associated with OS and was more significant than post-operative CEA level. However, for DFS, only CSTB score and negative pathological perineural invasion were independent predictors; post-operative CEA and CA199 level were not.
Serum carcinoembryonic antigen (CEA) is a glycoprotein anchored on the surface of glycosyl phosphatidylinositol (GPI) cells [16], which is the key to metastasis and dissemination of colon cancer cells [17]. It was usually measured in the pre-treatment examination of RC patients. The value of serum CEA level on prognosis has been widely discussed in related literature [18, 19] [17, 20]: Patients with elevated CEA levels before or after NCRT have poor tumour response and increased risk of recurrence [20, 21]. Researches also stated that the reduction ratio of pre- to post-CRT serum CEA levels might be a prognostic factor for DFS in RC patients with a pre-NCRT CEA of more than six ng/ml [22]. However, it was rarely reported prognostic value for post-operative CEA level in LARC patients. Our study revealed that lower post-operative CEA level associated with better prognosis, which was in consistence with many previous studies.
CA19-9 is an antigen expressed by the glycosylated extracellular MUC1 protein and plays an essential role in cancer invasion by indirectly enhancing cell adhesion and promoting angiogenesis [23]. Many studies showed that CA199 could be a prognosis predictor for RC patients [24–26]. Unfortunately, CA19-9 can be raised by several types of gastrointestinal cancer, such as esophageal cancer, colorectal cancer, and hepatocellular carcinoma [27–29]. Apart from cancer, elevated levels could be present in benign diseases, including pancreatitis, cirrhosis, and diseases of the bile ducts [30, 31]. Therefore, it failed to be widely used in the clinic to forecast the prognosis for RC patients, especially in LARC patients who underwent NCRT.
Instead of the single serum tumour biomarker, CSTB was a score that combined these two. We assumed that the CSTB score could predict prognosis in RC patients mainly for the following two reasons. First, the CSTB score was a combination of two significant serum tumour biomarker predictive factors with a physiological mechanism. Second, the application of the ROC curve, not just whether the tumour index exceeds the standard value, contributed to finding the best cut-off value of prognosis prediction. Therefore, we believed the CSTB score was capable of evaluating outcomes of LARC patients.
The prognostic value of CEA and CA199 were inspected by a few studies. Yang et al. manifested a significant connection between pre-operative CEA level and RC patients’ prognosis .In the study of Yang et al., low pre-operative CEA level was proved to be a valuable predictor in RC [32]. Zhang et al. reported that the elevated CA199 was an independent risk factor of worse prognosis in LARC patients [33]. However, none of them focused on combining post-operative CEA and CA199 level and specific on LARC patients undergoing NCRT. Consequently, we designed the present research to investigate the correlation between the CSTB score and prognosis in LARC patients undergoing NCRT, and the results suggested that the CSTB score < 2 was associated with significantly better OS and DFS.
Our study's most important clinical significance was as follows: Firstly, we focused on post-operative CEA and CA199 level instead of pre-treatment since post-operative indicators have a more robust predictive effect on prognosis. Moreover, we focused specifically on LARC patients undergoing NCRT, a research hot spot. Finally, we combined these two scores and adopted the ROC curve to determine the optimal cut-off point. CSTB score may not only assess the risk of LARC patients but also contributed to making treatment decisions. In detail, compared with LARC patients with low CSTB score, patients with high CSTB scores were indicated to be treated more aggressively, and post-operative adjuvant therapy may be more beneficial and adjustable to patients in the same circumstances.
The research had significant drawbacks. First, this was a retrospective study. Second, we determined 2.550 as the optimal cut-off value of post-operative CEA and 16.36 for CA199. The cut-off values may not be the most suitable. However, the ideas and methods in this research can be widely used the ideas and methods in this research can be widely used. Even the optimal cut-off may vary among different people, irrespective of the specific cut-off point, this study could still show the prognosis of patients with higher CEA CA199 level was poor.