J Cancer 2017; 8(19):4057-4064. doi:10.7150/jca.21365

Research Paper

Hazard rate of tumor recurrence over time in patients with colon cancer: implications for postoperative surveillance from three Japanese Foundation for Multidisciplinary Treatment of Cancer (JFMC) clinical trials

Hiromichi Maeda1*✉, Kosuke Kashiwabara2*, Toru Aoyama3, Koji Oba2, Michitaka Honda4, Shuhei Mayanagi5, Mitsuro Kanda6, Chikuma Hamada7, Sotaro Sadahiro8, Junichi Sakamoto9, 10, Shigetoyo Saji10, Takaki Yoshikawa11✉

1. Cancer Treatment Center, Kochi Medical School Hospital, Kochi University, Nankoku, Japan
2. Department of Biostatistics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
3. Department of Surgery, Yokohama City University, Yokohama, Japan
4. Department of Minimally Invasive Surgical and Medical Oncology, Fukushima Medical University, Fukushima, Japan
5. Department of Surgery, Keio University School of Medicine, Tokyo, Japan
6. Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan
7. Faculty of Engineering, Tokyo University of Science, Tokyo, Japan
8. Department of Surgery, Tokai University, Isehara, Japan
9. Tokai Central Hospital, Kakamigahara, Japan
10. Japanese Foundation for Multidisciplinary Treatment of Cancer, Tokyo, Japan
11. Department of Gastrointestinal Surgery, Kanagawa Cancer Center, Yokohama, Japan
*These authors equally contributed to this study.

Abstract

Purpose: Reliable risk estimates of recurrence are necessary to establish optimal postoperative surveillance strategies. The purpose of the present study was to clarify changes in the hazard rate (HR) for tumor recurrence over time in Japanese patients with colon cancer.

Methods: Data for 3984 patients from three clinical trials evaluating the benefit of adjuvant chemotherapy for colon cancer were analyzed. Estimated HRs were plotted over time for the entire cohort, as well as for node-positive and node-negative patients separately. The changes in risk were further analyzed according to eight clinical variables, and factors predictive of early (<3 years) and late (>3 years) recurrence were explored using Cox's regression analysis.

Results: In node-positive patients, there was a prominent HR peak 0.6 years after surgery, whereas HR remained at consistently low levels in node-negative patients. In node-positive patients, HR decreased steadily until 3 years, after which the decline in HR plateaued. Those with T4 tumors had a prominent HR peak around 1 year, including node-negative patients. The HR for T1/T2 Stage III colon cancers showed a similar pattern as that for T1-T3 node-negative colon cancers. Cox regression analysis revealed that a lack of adjuvant chemotherapy, positive node status, T3/T4 factors, and male gender predict early recurrence, whereas patients with lymph node metastasis, T4 tumors, and a lesser extent of lymph node removal have a higher risk of recurrence 3-4 years after surgery (P<0.05).

Conclusion: The present study supports the concept of intensive surveillance during the first 3 years after curative resection. However, a reduction in surveillance intensity may be acceptable for patients with T3 Stage II and T1/T2 Stage III colon cancer.

Keywords: pooled analysis, continuous-time hazard, node-positive patients, T1, T2, intensive surveillance

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.
How to cite this article:
Maeda H, Kashiwabara K, Aoyama T, Oba K, Honda M, Mayanagi S, Kanda M, Hamada C, Sadahiro S, Sakamoto J, Saji S, Yoshikawa T. Hazard rate of tumor recurrence over time in patients with colon cancer: implications for postoperative surveillance from three Japanese Foundation for Multidisciplinary Treatment of Cancer (JFMC) clinical trials. J Cancer 2017; 8(19):4057-4064. doi:10.7150/jca.21365. Available from http://www.jcancer.org/v08p4057.htm