Prognostic impact of carcinoembryonic antigen and carbohydrate antigen 19-9 in stage IV colorectal cancer patients after R0 resection

Abstract

Background

Although preoperative carcinoembryonic antigen (pre-CEA) and carbohydrate antigen 19-9 (pre-CA 19-9) are reportedly prognostic indicators for colorectal cancer (CRC), the prognostic roles of postoperative CEA (post-CEA) and CA 19-9 (post-CA 19-9) shortly after surgery have not been clarified in patients with curatively resected stage IV CRC. The aim of this study was to evaluate the predictive abilities of post-CEA and post-CA 19-9.

Methods

A total of 129 consecutive patients who had stage IV CRC and underwent R0 resection were retrospectively analyzed. Pre-CEA and post-CEA and CA 19-9 levels were measured within 1 mo before and 3 mo after surgery, respectively. Relapse-free survival (RFS) and overall survival were estimated using the Kaplan–Meier method, and multivariate analysis was performed using the Cox proportional hazards model.

Results

Pre-CEA was elevated (≥5.0 ng/mL) in 73.6% of the patients and remained elevated after surgery in 32.7% of the patients. Elevated post-CA 19-9 (≥50 U/mL) was observed in 9.5% of the patients. Neither elevated pre-CEA nor elevated pre-CA 19-9 was significantly associated with RFS but both elevated post-CEA and elevated post-CA 19-9 were associated with markedly reduced RFS (P = 0.0002 and P = 0.0004, respectively). When considered in combination, post-CEA and post-CA 19-9 significantly stratified RFS and was an independent predictive factor for recurrence (P = 0.0035), as was lymphatic invasion (P = 0.0015). Post-CA 19-9 was the only evident independent predictive factor for overall survival (P = 0.0336).

Conclusions

In patients with stage IV CRC who underwent curative resection, the combination of post-CEA and post-CA 19-9 at 3 mo after surgery was a potent prognostic indicator for recurrence.

Introduction

Approximately 25% of patients with colorectal cancer (CRC) have metastasis to one or more organs at the time of diagnosis.¹ Although these cases are classified as stage IV, which has the worst outcomes of all stages, complete surgical resection of both the primary lesion and distant metastases reportedly contributes to long survival times.² Thus, radical operations are currently performed in about one-fourth of patients with stage IV CRC,2, 3 and cases in which neoadjuvant chemotherapy enables complete resection of the metastasis are increasing alongside advances in anticancer drugs.⁴ However, the recurrence rate remains higher in patients with stage IV CRC who receive complete resection than those patients with other disease stages.5, 6 Accordingly, predictions of relapse risk in these patients are important to the treatment strategy after surgery. Lymph node metastasis, peritoneal invasion, primary tumor location, and other factors have been reported to be associated with recurrence in patients with stage IV disease;2, 7 yet, no definite predictive marker for recurrence has been established because stage IV includes a wide variety of cancer statuses, ranging from solitary liver metastasis to metastasis in multiple organs.

Preoperative carcinoembryonic antigen (pre-CEA) and carbohydrate antigen 19-9 (pre-CA 19-9) are two major tumor markers for CRC.8, 9, 10 CEA level is known to increase at the time of recurrence in many cases and is therefore used widely as a marker for postoperative surveillance in CRC.11, 12, 13 Pre-CEA and pre-CA 19-9 elevation have associations with recurrence7, 14, 15, 16, 17, 18, 19 suggesting the potential applicability of these markers as predictive factors. However, the roles of pre-CEA and pre-CA 19-9 have not been established fully in patients with stage IV disease, and the roles of CEA and CA 19-9 shortly after surgery have not been investigated previously. No study has compared the predictive abilities of these markers, as measured both preoperatively and postoperatively. Under the hypothesis that postoperative levels of these markers reflect the microscopic residual cancer and consequently may be superior to preoperative markers for predicting cancer recurrence, we investigated the prognostic impacts of CEA and CA 19-9 in patients who had stage IV disease, received curative resection, and had a high risk of recurrence.