Neoadjuvant therapy in locally advanced colon cancer: a meta-analysis and systematic review

Chin Kai Cheong; Kameswara Rishi Yeshayahu Nistala; Cheng Han Ng; Nicholas Syn; Heidi Sian Ying Chang; Raghav Sundar; Soon Yu Yang; Choon Seng Chong

doi:10.21037/jgo-20-220

Neoadjuvant therapy in locally advanced colon cancer: a meta-analysis and systematic review

J Gastrointest Oncol. 2020 Oct;11(5):847-857. doi: 10.21037/jgo-20-220.

Authors

Chin Kai Cheong¹, Kameswara Rishi Yeshayahu Nistala¹, Cheng Han Ng¹, Nicholas Syn¹, Heidi Sian Ying Chang², Raghav Sundar^{1

3

4}, Soon Yu Yang⁵, Choon Seng Chong^{1

2}

Affiliations

¹ Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
² Department of Surgery, University Surgical Cluster, National University Hospital, Singapore, Singapore.
³ Department of Haematology-Oncology, National University Cancer Institute, Singapore (NCIS), National University Health System, Singapore, Singapore.
⁴ The N.1 Institute for Health, National University of Singapore, Singapore, Singapore.
⁵ Department of Radiation Oncology, National University Cancer Institute, Singapore (NCIS), National University Health System, Singapore, Singapore.

Abstract

Background: The role of perioperative or neoadjuvant chemotherapy for locally advanced colon cancer is unclear. Emerging evidence such as the FOXTROT trial is challenging the conventional norm of upfront operation for these patients. However, these trials have yet to reach statistical significance.

Methods: MEDLINE, Embase, Cochrane Library, China Knowledge Resource Integrated Database (CNKI) and ClinicalTrials.gov were searched. Randomized controlled trials (RCTs) and observational studies of patients with locally advanced colon cancer were included. The intervention arm was neoadjuvant chemotherapies while the comparator arm was adjuvant chemotherapies. Studies which reported outcomes of interests included overall survival, disease-free survival, R0 resection rate, perioperative complications and adverse effects of chemotherapy were chosen.

Results: We identified five eligible randomized trials and two observational studies, including 29,504 patients. Neoadjuvant therapies exhibited statistically significant improvement in overall survival [hazard ratio (HR) =0.76, 95% confidence interval (CI): 0.65-0.89, P=0.0005], and disease-free survival (HR =0.74, 95% CI: 0.58-0.95, P=0.02). R0 resection rate fell slightly short of significance [odds ratio (OR) =1.86, 95% CI: 0.95-3.62, P=0.07]. Risk of peri-operative complications did not differ between groups when examining abdominal infection [risk ratio (RR) =1.14, 95% CI: 0.59-2.18, P=0.70] and anastomotic leakage (RR =0.83, 95% CI: 0.53-1.31, P=0.42). No statistical differences in complications from chemotherapy were reported.

Conclusions: This meta-analysis highlights the potential survival benefit of neoadjuvant chemotherapy compared to adjuvant chemotherapy for locally advanced colon cancer, without an increase in surgical morbidity. Neoadjuvant or perioperative approaches may be considered an alternative to upfront surgery followed by chemotherapy for locally advanced colon cancer.

Keywords: Neoadjuvant therapy; colonic neoplasms; meta-analysis.