Retrospective Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Jan 15, 2019; 11(1): 17-27
Published online Jan 15, 2019. doi: 10.4251/wjgo.v11.i1.17
Prognostic significance of perioperative tumor marker levels in stage II/III gastric cancer
Yasuhito Suenaga, Mitsuro Kanda, Seiji Ito, Yoshinari Mochizuki, Hitoshi Teramoto, Kiyoshi Ishigure, Toshifumi Murai, Takahiro Asada, Akiharu Ishiyama, Hidenobu Matsushita, Chie Tanaka, Daisuke Kobayashi, Michitaka Fujiwara, Kenta Murotani, Yasuhiro Kodera
Yasuhito Suenaga, Hitoshi Teramoto, Department of Surgery, Yokkaichi Municipal Hospital, Yokkaichi 510-8567, Japan
Yasuhito Suenaga, Seiji Ito, Department of Gastroenterological Surgery, Aichi Cancer Center, Nagoya 464-8681, Japan
Mitsuro Kanda, Chie Tanaka, Daisuke Kobayashi, Michitaka Fujiwara, Yasuhiro Kodera, Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan
Yoshinari Mochizuki, Department of Surgery, Komaki Municipal Hospital, Komaki 485-8520, Japan
Kiyoshi Ishigure, Department of Surgery, Konan Kosei Hospital, Konan 483-8704, Japan
Toshifumi Murai, Department of Surgery, Ichinomiya Municipal Hospital, Ichinomiya 491-8558, Japan
Takahiro Asada, Department of Surgery, Gifu Prefectural Tajimi Hospital, Tajimi 507-8522, Japan
Akiharu Ishiyama, Department of Surgery, Okazaki City Hospital, Okazaki 444-8553, Japan
Hidenobu Matsushita, Department of Surgery, Tosei General Hospital, Seto 489-8642, Japan
Kenta Murotani, Biostatistics Center, Graduate School of Medicine, Kurume University, Kurume 830-0011, Japan
Author contributions: Suenaga Y wrote the manuscript; Kanda M and Kodera Y revised the text and contributed to the scientific analysis in the manuscript; Ito S, Mochizuki Y, Teramoto H, Ishigure K, Murai T, Asada T, Ishiyama A, Matsushita H, Tanaka C, Kobayashi D and Fujiwara M contributed to data collection; Murotani K conducted the statistical analyses.
Institutional review board statement: The study was reviewed and approved by the Institutional Review Boards of the all participating hospitals.
Informed consent statement: This study conforms to the ethical guidelines of the World Medical Association Declaration of Helsinki - Ethical Principles for Medical Research Involving Human Subjects, and written informed consent for the use of clinical data was obtained from all patients.
Conflict-of-interest statement: The authors declare that they have no conflicts of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Mitsuro Kanda, MD, PhD, Research Fellow, Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan. m-kanda@med.nagoya-u.ac.jp
Telephone: +81-52-7442249 Fax: +81-52-7442252
Received: August 16, 2018
Peer-review started: August 17, 2018
First decision: October 5, 2018
Revised: October 28, 2018
Accepted: December 5, 2018
Article in press: December 5, 2018
Published online: January 15, 2019
Processing time: 152 Days and 7.2 Hours
Abstract
AIM

To evaluate the prognostic significance of perioperative carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) levels in stage II/III gastric cancer.

METHODS

From a multi-institutional retrospective database compiled by integrating clinical data from nine institutions, data of 998 patients who underwent curative resection for stage II/III gastric cancer between 2010 and 2014 were retrieved and analyzed. The prognostic impact of the preoperative and postoperative levels and chronological changes in CEA, CA19-9 and their combination were evaluated. To test whether postoperative adjuvant chemotherapy alters the prognostic impact of perioperative CEA and CA19-9 levels, the hazard ratios for mortality were compared between patients who underwent surgery alone and patients who underwent surgery followed by adjuvant chemotherapy.

RESULTS

The prognostic impact of postoperative CEA and CA19-9 was superior to that of the preoperative levels. Multivariable analysis identified high postoperative CEA and CA19-9 levels as independent prognostic factors for overall survival. Disease-free survival rates clearly decreased in a stepwise manner in association with postoperative CEA and CA19-9 levels, and patients with high levels of both markers showed significantly poorer prognosis than other patient groups. When we analyzed perioperative changes in serum CEA and CA19-9 levels, patients with high levels before and after surgery had the worst disease-free survival rates among all patient groups. Patients with normalized CEA levels after surgery had a significantly lower disease-free survival rate than those with normal perioperative levels, whereas patients with normalized CA19-9 levels after surgery had equivalent survival to those with normal perioperative levels. The prognostic impact of high CEA levels was observably smaller in patients who underwent adjuvant chemotherapy than in patients who underwent surgery alone, whereas that of high CA19-9 was greater in patients who underwent adjuvant chemotherapy. High postoperative CEA levels were significantly associated with an increased prevalence of liver, lung and bone recurrences, and high postoperative CA19-9 levels were significantly associated with increased frequencies of lymph node and liver recurrences.

CONCLUSION

The evaluation of serum CEA and CA 19-9 levels both before and after surgery provides useful information for precise risk stratification after curative gastrectomy.

Keywords: Gastric cancer; Carcinoembryonic antigen; Carbohydrate antigen 19-9; Perioperative levels; Prognosis

Core tip: Although the outcomes of patients with advanced gastric cancer have gradually improved with the development of adjuvant therapies, a large number of patients experience disease recurrence after curative gastrectomy. To optimize the management of each individual patient, accurate markers to predict prognosis are needed. In this multicenter dataset analysis, we found that evaluation of the serum carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) levels both before and after surgery provides more precise risk stratification of patients with stage II/III gastric cancer. Patients with high postoperative CEA and CA19-9 levels are at high risk of disease recurrence, and intensive postoperative management to detect hematogenous recurrences should be considered.