Simultaneous Versus Delayed Resection for Initially Resectable Synchronous Colorectal Cancer Liver Metastases: A Prospective, Open-Label, Randomised, Controlled Trial

Abstract

Background: Whether synchronous colorectal cancer liver metastases should be resected simultaneously with primary cancer or whether the procedure should be delayed remains controversial. Methods: This randomised controlled trial recruited patients from 10 French referral centres. Adults with colorectal cancer and synchronous resectable liver metastases were assigned to either simultaneous or delayed resection of the metastases. The primary outcome was the incidence of a major complication within 60 days following surgery. Secondary outcomes included overall and disease-free survival. Findings: A total of 105 patients were recruited between March 2nd 2006 and December 21st 2015. Eighty-five patients (39 and 46 in the simultaneous- and delayed-resection groups respectively) were analysed. The percentage of major perioperative complications did not differ between groups (respectively 49% vs. 46% in the simultaneous- and delayed-resection groups, adjusted OR 0·84, 95% CI 0·35-2·01; p=0·70, logistic regression). The percentages of complications at colorectal and w 28% 13% ( =0·08 χ2 ) 15% 17% ( =0·80 χ2 ) - and delayed-resection groups respectively. In the delayed-resection group, eight patients did not reach the liver resection stage due to disease progression for 6. Overall and diseasef w 46% 28% ( =0·09 χ2 ) 23% 13% ( =0·23 χ2 est), in the simultaneous- and delayed-resection groups respectively. Overall (but not disease-free) survival was improved in the simultaneous- compared to the delayed-resection group (p=0·048 and p=0·51 respectively, Cox models). Interpretation: Colorectal cancer and synchronous liver metastases can be resected simultaneously without increasing the risk of perioperative complications. Delayed resection exposes patients to the risk of disease progression and impairs overall survival. Clinical Trial Registration Number: clinicaltrials.gov Identifier: NCT00264979. Funding Statement: French Ministry of Health (Programme Hospitalier de Recherche Clinique 2004) and Association pour la Recherche sur le Cancer (ARC) Declaration of Interests: The authors state: We have no competing interests to report. Ethics Approval Statement: This prospective open-label randomised controlled parallel-group trial involved ten French tertiary referral centres, specialised in colorectal and hepatobiliary surgery. The study protocol was approved by the Consultative Committee for the Protection of Individuals taking part in Biomedical Research, Rennes, France, on April 6th 2005 (protocol n° 05/11-538).