Postoperative chemotherapy with single-agent fluoropyrimidines after resection of colorectal cancer liver metastases: A meta-analysis of randomised trials

Abstract

Surgical resection is the only option of cure for patients with metastatic colorectal cancer. Risk of recurrence after metastasectomy is around 75%. Use of adjuvant chemotherapy after metastasectomy is controversial. Aim To address whether adjuvant systemic therapy after colorectal cancer metastasectomy offers any survival benefit compared with surgery alone. Methods Systematic review of literature and meta-analysis of all available randomised evidence. Relative hazards (RHs) were summarised across trials and heterogeneity was assessed with the Q and I2 statistics. Results Five trials were eligible. Three trials, all using single-agent fluoropyrimidine chemotherapy, presented data valuable for analyses. 482 patients were included in the meta-analysis: 238 randomly assigned to receive postoperative chemotherapy and 244 to metastasectomy only. We found no overall survival (OS) benefit with the use of postoperative single-agent fluoropyrimidines compared with surgery alone, even if a trend for benefit was observed (relative hazard (RH)=0.781, 95% CI 0.593 to 1.030, p=0.080). Significant disease-free survival benefit with the use of postoperative chemotherapy was observed (RH=0.645, 95% CI 0.509 to 0.818, p=0.001). No quality of life (QL) data were available. All trials showed accrual delay, two stopped and one recruiting after 10 years. Long follow-up needs were evidenced since OS curves split only after 3.5 years. Conclusions No OS benefit was documented from the use of postoperative monochemotherapy. Metastasectomy alone continues to be the standard of care. Combination chemotherapy regimens should be evaluated along with QL assessment in future trials appropriately designed for long-term accrual and follow-up.