Randomised controlled trials (RCTs), non-randomised controlled trials, well-designed cohort studies and observational studies (with at least 20 patients) where systemic chemotherapy was used in patients with resectable colorectal liver metastases before hepatectomy (neoadjuvant chemotherapy) were eligible for inclusion. The eligible systemic chemotherapy agents were: 5-fluorouracil, leucovorin, oxaliplatin, irinotecan, bevacizumab, cetuximab or other agents administered intravenously. Studies that used hybrid techniques (hepatectomy combined with ablation) as part of the aim of expanding the criteria for resection of colorectal liver metastases were also included. Studies that used ablative techniques after neoadjuvant chemotherapy were excluded.
The primary outcomes of interest were response to neoadjuvant chemotherapy (radiological or pathological), disease-free survival and overall survival. Secondary outcomes were surgical morbidity and mortality.
Most of the included patients had hepatic-only metastases. The median number of lesions ranged from two to seven; their median maximum size was 4cm (range 3 to 5cm). Approximately 80% of included patients had less than four lesions. The most common neoadjuvant therapy agents administered in included studies were 5-fluorouracil, leucovorin, oxaliplatin, and irinotecan either alone or in combination (FOLFOX or FOLFIRI). The median number of chemotherapy cycles was six (range two to 11), with median duration of four months (range three to eight months).
Two reviewers independently selected papers for inclusion and disagreements were resolved by discussion and consensus.