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

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.

Critical reappraisal of neoadjuvant concurrent chemoradiotherapy for treatment of locally advanced colon cancer

“…For non-hematologic AEs, the incidence of severe AEs was <10%. This result was consistent with our previous studies [ 6 , 11 , 19 , 48 ], and we suggested that neoadjuvant CCRT is a safe and tolerable treatment for patients with LACC.…”

“…Obviously, an accurate CT scan image is essential in our treatment program. Many articles have described that CT is a reliable examination to assess the colon cancer stage and devise the subsequent surgical plan [ 7 , 11 , 12 , 16 , 19 ].…”

“…In a systemic review in 2020, Cheong et al . found that 12.5%–22% of LACC patients who underwent neoadjuvant chemotherapy developed granulocytopenia [ 19 ], and Zhou et al . reported that 4.3% and 21.7% of LACC patients who underwent neoadjuvant chemotherapy developed moderate to severe anemia and leukopenia, respectively [ 48 ].…”

“…Another possible advantage of neoadjuvant CCRT is the eradication of occult systemic micro-metastasis, which might decrease cancer DM [ 8 , 12 , 19 ]. With tumor regression and shrinkage, surgical resection can be less challenging, resulting in fewer postoperative complications [ 7 , 8 , 18 , 19 ]. Moreover, patients are less likely to delay adjuvant therapy due to postoperative complication-related infection or malnutrition [ 12 ].…”

Emergency resection or diverting stoma followed by elective resection in patients with colonic obstruction due to locally advanced cancer: a national cohort study

“…Another possible benefit is the option of neoadjuvant chemotherapy, which has recently been shown to improve oncological outcomes in locally advanced colon cancer [25, 26]. Neoadjuvant chemotherapy can result in downstaging and tumour regression in patients with obstructing or high risk colon cancer [27–30]. In the present study, 24% of the patients with right‐sided colon cancer and 29% of the patients with left‐sided colon cancer that were diverted received neoadjuvant chemotherapy.…”