Systematic review of systemic adjuvant, neoadjuvant and perioperative chemotherapy for resectable colorectal-liver metastases

HPB (Oxford). 2016 Jun;18(6):485-93. doi: 10.1016/j.hpb.2016.03.001. Epub 2016 Apr 20.

Abstract

Introduction: The role of systemic chemotherapy in patients with resectable colorectal liver metastases (CRLM) is ambiguous. The aim of this review was to compare the outcomes of regimens using systemic neoadjuvant, adjuvant or perioperative (combination of pre and postoperative) chemotherapy, for the treatment of resectable CRLM.

Methods: MEDLINE was searched for articles investigating the use of chemotherapy for adults with resectable CRLM. Randomized controlled trials reporting overall survival (OS), disease-free survival (DFS) and grade 3-4 adverse events (AEs) were screened for inclusion. PROSPERO record: CRD42015020609.

Results: Four trials met the inclusion criteria (1098 patients). No significant improvement in median OS was achieved with chemotherapy/surgery compared with surgery-alone. Two trials demonstrated a significant improvement in DFS with chemotherapy/surgery compared to surgery-alone (Hazard ratio 0.78 (0.61-0.99) p = 0.04 and HR 0.66 (0.46-0.96) p = 0.03). Fluorouracil/folinic acid alone had a lower incidence of AEs than combination therapies, and the addition of cetuximab shortened DFS in one trial (HR 1.48 (1.04-2.12) p = 0.03).

Conclusion: There is a lack of adequately powered trials of chemotherapy in combination with liver resection for CRLM, partly due to difficulties in recruitment. In an unselected patient group, FOLFOX in combination with liver resection appears to improve DFS compared to surgery-alone, but trials are underpowered for OS. Future trials will require prospective stratification of patients based on biomarkers predictive of response.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Chemotherapy, Adjuvant
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / pathology*
  • Disease Progression
  • Disease-Free Survival
  • Female
  • Hepatectomy* / adverse effects
  • Hepatectomy* / mortality
  • Humans
  • Liver Neoplasms / mortality
  • Liver Neoplasms / secondary*
  • Liver Neoplasms / therapy*
  • Male
  • Middle Aged
  • Neoadjuvant Therapy* / adverse effects
  • Neoadjuvant Therapy* / mortality
  • Neoplasm Recurrence, Local
  • Risk Factors
  • Survival Analysis
  • Time Factors
  • Treatment Outcome