GastrointestinalPrognostic impact of carcinoembryonic antigen and carbohydrate antigen 19-9 in stage IV colorectal cancer patients after R0 resection
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.
Section snippets
Patients
For this retrospective study, data were collected on 129 consecutive patients who had stage IV CRC with simultaneous distant metastasis, and who underwent surgical R0 resection between July 2004 and May 2014 at The University of Tokyo Hospital. Patients were excluded if they had Lynch syndrome, inflammatory bowel disease, or concomitant primary cancer in extracolic organs at the operation. All enrolled patients had synchronous distant metastasis at the time of the primary operation, and
Results
The clinicopathologic characteristics of the 129 patients enrolled in the present study are summarized in Table 1. Pre-CEA levels were high in 73.6% of the patient cohort, of whom only 32.7% had CEA that remained high after surgery. High pre-CA 19-9 (32.0%) was less common than pre-CEA high and decreased to 9.5% postoperatively. Table 2 presents the associations between post-CEA, post-CA 19-9, their combination, and preoperative clinicopathologic variables. Post-CEA only showed a significant
Discussion
Elevated levels of pre-CEA are reportedly more common in patients with advanced tumor stages,21, 22, 23 and the reported prevalence of elevated pre-CEA is 71.3% to 81.4% in patients with stage IV CRC.2, 24 In the present study, pre-CEA levels were elevated in 73.6% of the patients, corroborating previous reports. Although preoperative elevation of CA 19-9 has not been investigated as often as CEA, preoperative elevation of CA 19-9 has been demonstrated in up to 51.8%-53% of patients with stage
Acknowledgment
Authors' contributions: S.A. acquired, analyzed, and interpreted the data, drafted the article, and gave approval to the final submission. K.K. conceptualized and designed the study, interpreted the data, critically revised the manuscript, and gave approval to the final submission. S.I. and H.N. acquired and interpreted the data, critically revised the manuscript, and gave approval to the final submission. K.H., T.K., and T.T. acquired the data, and gave approval to the final submission. T.W.
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