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
ARTICLE HIGHLIGHTS
Research background

There certainly remains a patient population with disease recurrence after curative gastrectomy for advanced gastric cancer. The accurate prediction of patient prognosis is an important task in optimizing management for each individual patient. Carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) are have long been widely used for the diagnosis and monitoring of gastric cancer. However, their performance remains unsatisfactory and further improvement is needed.

Research motivation

In our previous paper, we reported that the risk of recurrences can be stratified by examining both the preoperative and postoperative levels of serum CEA and CA19-9. However, our previous study suffered from caveats such as being a single institution study with a small sample size and variabilities in the adjuvant treatments given due to the change in standard of care during the acquisition of data. Our data should be verified by a larger and modern cohort and the influence of adjuvant chemotherapy implementation should be considered in evaluating the prognostic ability of tumor markers.

Research objectives

To reappraise the prognostic significance of perioperative serum CEA and CA 19-9 levels in patients with stage II/III gastric cancer, we designed a large-scale multi-institutional retrospective database and analyzed patients who underwent resection of gastric cancer between 2010 and 2014.

Research methods

Data of 998 patients who underwent curative resection for stage II/III gastric cancer between 2010 and 2014 at the nine participating institutions was analyzed. Prognostic impact of the preoperative and postoperative levels and chronological changes in CEA, CA19-9 and their combination were evaluated. The hazard ratios for mortality were compared between patients who underwent surgery alone and patients who underwent surgery followed by adjuvant chemotherapy.

Research results

Postoperative levels had better prognostic values compared to preoperative levels. Disease-free survival rates gradually reduced according to postoperative CEA and CA19-9 levels, and patients with high levels of both markers had the worst prognosis. 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 CA19-9 was greater in patients who underwent adjuvant chemotherapy.

Research conclusions

We herein showed the combination and preoperative measurement of serum CEA and CA 19-9 levels can be a promising tool to predict prognosis of patients with stage II/III gastric cancer. Using a multi-institutional large-size database, our data was successfully refined and more convincing than the previous one.

Research perspectives

Serum CEA and CA 19-9 levels have distinct dynamics and prognostic significance. Intensive postoperative management should be considered. The appropriate timing of measurement and optimal cutoff values of perioperative tumor markers for maximal risk stratification are unresolved issues. In the future, novel biomarkers for gastric cancer with high sensitivity and specificity are expected to be available after validation in large-size clinical trials.