Systematic Review of Randomized and Nonrandomized Trials of the Clinical Response and Outcomes of Neoadjuvant Systemic Chemotherapy for Resectable Colorectal Liver Metastases

Background. Neoadjuvant chemotherapy prior to hepatectomy in patients with resectable colorectal liver metastases (CLM) may facilitate the resectability of the liver lesions and treat occult metastasis but may also lead to hepatic parenchyma damage. There is argument over the oncologic benefit of this practice in patients who would already be suitable for a curative hepatectomy. Methods. Extensive literature search of databases (MEDLINE and PubMed) to identify published studies of preoperative systemic chemotherapy for resectable CLM was undertaken with clinical response to treatment and survival outcomes as the endpoints. Results. Twenty-three studies were reviewed: 1 phase III randomized control trial, 3 phase II studies, and 19 observational studies, comprising 3,278 patients. Objective (complete/partial) radiological response was observed in 64% (range 44-100%) [complete 4% (range 0-38%), partial 52% (range 10-90%)] of patients after neoadjuvant chemotherapy. Pathologically, a median of 9% (range 2-24%) and 36% (range 20-60%) had complete and partial response, respectively. Of patients, 41% (range 0-65%) had stable or progressive disease whilst on neoadjuvant chemotherapy. Median disease-free survival (DFS) was 21 (range 11-40) months. Median overall survival (OS) was 46 (range 20-67) months. Conclusion. Current evidence suggests that objective response to neoadjuvant chemotherapy may be achieved with improvement in DFS in patients with resectable CLM. A prospective randomized trial of neoadjuvant therapy versus adjuvant therapy after liver resection is required to determine the optimal perisurgical treatment regimen.