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.AimTo address whether adjuvant systemic therapy after colorectal cancer metastasectomy offers any survival benefit compared with surgery alone.MethodsSystematic 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.ResultsFive 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.ConclusionsNo 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.

Prognostic impact of additive chemotherapy after curative resection of metachronous colorectal liver metastasis: a single-centre retrospective study

“…A recent meta-analysis of three randomized trials detected a statistically significant prolonged DFS for patients with CRLM who had received additive CTx in comparison to patients without CTx. However, with regard to patients’ OS a calculation of the survival benefit after additive CTx missed the level of statistical significance closely [ 20 , 29 ]. Other retrospective studies identified a survival advantage of additive CTx for certain patient subgroups.…”

“…While some studies have demonstrated a significantly improved disease-free survival (DFS) after additive chemotherapy (CTx) for patients with CRLM, statistical significance was missing for patients’ OS despite a clearly prolonged median OS [ 19 , 20 ]. In addition, most of the current evidence regarding CRLM includes patients with synchronous and metachronous CRLM resulting in heterogeneous patient cohorts [ 21 – 23 ].…”

Applicability of postoperative carcinoembryonic antigen levels in determining post-liver-resection adjuvant chemotherapy regimens for colorectal cancer hepatic metastasis

“…[18][19][20] Moreover, some studies have reported the nonsignificant effects of adjuvant chemotherapy on OS after LR. [21][22][23] Few recent studies have shown that doublet combination chemotherapy has no significant benefit or even has disadvantages compared with monochemotherapy. [17,24] Moreover, the beneficial effects of additional bioagents with cytotoxic chemotherapy in an adjuvant setting remain inconsistent.…”

Role of chemotherapy in resectable liver metastases from colorectal cancer: food for thought from pooled evidence

“…Despite nearly 500 patients being included, only a positive trend for an overall survival advantage was observed from the use of adjuvant chemotherapy. 6 …”

“…Considering the enormous accrual difficulties encountered in post-metastasectomy trials and the long survival follow-up required in this setting, 6 the scientific community (physicians, health authorities, academia and industry) has to take the necessary concerted actions in order to enrol patients in well-designed and informative trials.…”