Observational Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Dec 15, 2020; 12(12): 1428-1442
Published online Dec 15, 2020. doi: 10.4251/wjgo.v12.i12.1428
Outcomes of neoadjuvant chemoradiotherapy followed by radical resection for T4 colorectal cancer
Chun-Ming Huang, Ching-Wen Huang, Cheng-Jen Ma, Hsiang-Lin Tsai, Wei-Chih Su, Tsung-Kun Chang, Ming-Yii Huang, Jaw Yuan Wang
Chun-Ming Huang, Ming-Yii Huang, Department of Radiation Oncology, Kaohsiung Medical University Hospital, Kaohsiung 80145, Taiwan
Ching-Wen Huang, Hsiang-Lin Tsai, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80145, Taiwan
Cheng-Jen Ma, Wei-Chih Su, Tsung-Kun Chang, Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung 80145, Taiwan
Jaw Yuan Wang, Department of Surgery and Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
Author contributions: Wang JY and Huang MY contributed equally to this paper; Wang JY conceived the concept of the study and supervised the study; Huang CM wrote and drafted the manuscript; Huang CW, Ma CJ, Tsai HL, Su WC, and Chang TK collected and collated the clinical data; Huang MY and Huang CM conducted the statistical analysis and interpreted the results; all authors read and approved the final manuscript.
Supported by the grants through funding from the Ministry of Science and Technology, No. MOST109-2314-B-037-035, No. MOST109-2314-B-037-040, and No. MOST109-2314-B-037-046-MY3; the Ministry of Health and Welfare funded by Health and Welfare Surcharge of Tobacco Products, No. MOHW109-TDU-B-212-124026; the Kaohsiung Medical University Hospital and the Kaohsiung Municipal Ta-Tung Hospital, No. S10903, No. KMUH108-8R34, No. KMUH108-8R35, No. KMUH108-8M33, No. KMUH108-8M35, No. KMUH108-8M36, No. KMUH-DK109003, and No. KMUH-DK109005-3.
Institutional review board statement: This study was approved by the Institutional Review Board of Kaohsiung Medical University Hospital (KMUHIRB-EII-20190281).
Informed consent statement: The informed consent was waived.
Conflict-of-interest statement: The authors declare that they have no conflicts of interest to disclose.
Data sharing statement: There are no additional data.
STROBE statement: All authors have read the STROBE statement checklist of items. The manuscript was prepared and revised according to the STROBE statement checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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: Jaw Yuan Wang, MD, PhD, Professor, Department of Surgery and Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, No. 100 Tz-You 1st Road, Kaohsiung 80708, Taiwan. cy614112@ms14.hinet.net
Received: August 26, 2020
Peer-review started: August 26, 2020
First decision: October 21, 2020
Revised: November 10, 2020
Accepted: November 17, 2020
Article in press: November 17, 2020
Published online: December 15, 2020
Abstract
BACKGROUND

Patients with clinical T4 colorectal cancer (CRC) have a poor prognosis because of compromised surgical margins. Neoadjuvant therapy may be effective in downstaging tumors, thereby rendering possible radical resection with clear margins.

AIM

To evaluate tumor downsizing and resection with clear margins in T4 CRC patients undergoing neoadjuvant concurrent chemoradiotherapy followed by surgery.

METHODS

This study retrospectively included 86 eligible patients with clinical T4 CRC who underwent neoadjuvant concurrent chemoradiotherapy followed by radical resection. Neoadjuvant therapy consisted of radiation therapy at a dose of 45-50.4 Gy and chemotherapy agents, either FOLFOX or capecitabine. A circumferential resection margin (CRM) of < 1 mm was considered to be a positive margin. We defined pathological complete response (pCR) as the absence of any malignant cells in a specimen, including the primary tumor and lymph nodes. A multivariate logistic regression model was used to identify independent predictive factors for pCR.

RESULTS

For 86 patients who underwent neoadjuvant chemoradiotherapy and surgery, the rate of pCR was 14%, and the R0 resection rate was 91.9%. Of the 61 patients with rectal cancer, 7 (11.5%) achieved pCR and 5 (8.2%) had positive CRMs. Of the 25 patients with colon cancer, 5 (20%) achieved pCR and 2 (8%) had positive CRMs. We observed that the FOLFOX regimen was an independent predictor of pCR (P = 0.046). After a median follow-up of 47 mo, the estimated 5-year overall survival (OS) and disease-free survival (DFS) rates were 70.8% and 61.4%, respectively. Multivariate analysis revealed that a tumor with a negative resection margin was associated with improved DFS (P = 0.014) and OS (P = 0.001). Patients who achieved pCR exhibited longer DFS (P = 0.042) and OS (P = 0.003) than those who did not.

CONCLUSION

Neoadjuvant concurrent chemoradiotherapy engenders favorable pCR and R0 resection rates among patients with T4 CRC. The R0 resection rate and pCR are independent prognostic factors for patients with T4 CRC.

Keywords: T4, Chemoradiotherapy, Pathological complete response, R0 resection, Colorectal cancer, Survival

Core Tip: Patients with clinical T4 colorectal cancer have a poor prognosis because of compromised surgical margins. This retrospective study demonstrated that neoadjuvant chemoradiotherapy resulted in high rates of pathological complete response and complete resection for patients with T4 colorectal cancer. An aggressive approach that entails implementing the FOLFOX regimen before, during, and after irradiation is safe and can improve pathological complete response rates. Negative resection margins and pathological complete response are significantly associated with survival.