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



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.



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).



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.
Department of Clinical Surgery, University of Edinburgh, Royal Infirmary of Edinburgh, 51 Little France Crescent, Edinburgh EH16 4SA, UK.
Emily
E
Khoo
Department of Clinical Surgery, University of Edinburgh, Royal Infirmary of Edinburgh, 51 Little France Crescent, Edinburgh EH16 4SA, UK.
Stephen
S
O'Neill
Edinburgh Cancer Centre, University of Edinburgh, Western General Hospital, Crewe Road South, Edinburgh EH4 2XR, UK.
Ewan
E
Brown
Department of Clinical Surgery, University of Edinburgh, Royal Infirmary of Edinburgh, 51 Little France Crescent, Edinburgh EH16 4SA, UK.
Stephen J
SJ
Wigmore
Department of Clinical Surgery, University of Edinburgh, Royal Infirmary of Edinburgh, 51 Little France Crescent, Edinburgh EH16 4SA, UK. Electronic address: ewen.harrison@ed.ac.uk.
Ewen M
EM
Harrison
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D015179:Colorectal Neoplasms / Q000401:mortality / Q000473:pathology*; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006498:Hepatectomy / Q000009:adverse effects / Q000401:mortality; D006801:Humans; D008113:Liver Neoplasms / Q000401:mortality / Q000556:secondary* / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000009:adverse effects / Q000401:mortality; D009364:Neoplasm Recurrence, Local; D012307:Risk Factors; D016019:Survival Analysis; D013997:Time Factors; D016896:Treatment Outcome