The clinical effectiveness and cost-effectiveness of ablative therapies in the management of liver metastases: systematic review and economic evaluation.
BACKGROUND
Many deaths from cancer are caused by metastatic burden. Prognosis and survival rates vary, but survival beyond 5 years of patients with untreated metastatic disease in the liver is rare. Treatment for liver metastases has largely been surgical resection, but this is feasible in only approximately 20-30% of people. Non-surgical alternatives to treat some liver metastases can include various forms of ablative therapies and other targeted treatments.


OBJECTIVE
To evaluate the clinical effectiveness and cost-effectiveness of the different ablative and minimally invasive therapies for treating liver metastases.


METHODS
Electronic databases including MEDLINE, EMBASE and The Cochrane Library were searched from 1990 to September 2011. Experts were consulted and bibliographies checked.


METHODS
Systematic reviews of the literature were undertaken to appraise the clinical effectiveness and cost-effectiveness of ablative therapies and minimally invasive therapies used for people with liver metastases. Studies were any prospective study with sample size greater than 100 participants. A probabilistic model was developed for the economic evaluation of the technologies where data permitted.


RESULTS
The evidence assessing the clinical effectiveness and cost-effectiveness of ablative and other minimally invasive therapies was limited. Nine studies of ablative therapies were included in the review; each had methodological shortcomings and few had a comparator group. One randomised controlled trial (RCT) of microwave ablation versus surgical resection was identified and showed no improvement in outcomes compared with resection. In two prospective case series studies that investigated the use of laser ablation, mean survival ranged from 41 to 58 months. One cohort study compared radiofrequency ablation with surgical resection and five case series studies also investigated the use of radiofrequency ablation. Across these studies the median survival ranged from 44 to 52 months. Seven studies of minimally invasive therapies were included in the review. Two RCTs compared chemoembolisation with chemotherapy only. Overall survival was not compared between groups and methodological shortcomings mean that conclusions are difficult to make. Two case series studies of laser ablation following chemoembolisation were also included; however, these provide little evidence of the use of these technologies in combination. Three RCTs of radioembolisation were included. Significant improvements in tumour response and time to disease progression were demonstrated; however, benefits in terms of survival were equivocal. An exploratory survival model was developed using data from the review of clinical effectiveness. The model includes separate analyses of microwave ablation compared with surgery and radiofrequency ablation compared with surgery and one of radioembolisation in conjunction with hepatic artery chemotherapy compared with hepatic artery chemotherapy alone. Microwave ablation was associated with an incremental cost-effectiveness ratio (ICER) of £3664 per quality-adjusted life-year (QALY) gained, with microwave ablation being associated with reduced cost but also with poorer outcome than surgery. Radiofrequency ablation compared with surgical resection for solitary metastases < 3 cm was associated with an ICER of -£266,767 per QALY gained, indicating that radiofrequency ablation dominates surgical resection. Radiofrequency ablation compared with surgical resection for solitary metastases ≥ 3 cm resulted in poorer outcomes at lower costs and a resultant ICER of £2538 per QALY gained. Radioembolisation plus hepatic artery chemotherapy compared with hepatic artery chemotherapy was associated with an ICER of £37,303 per QALY gained.


CONCLUSIONS
There is currently limited high-quality research evidence upon which to base any firm decisions regarding ablative therapies for liver metastases. Further trials should compare ablative therapies with surgery, in particular. A RCT would provide the most appropriate design for undertaking any further evaluation and should include a full economic evaluation, but the group to be randomised needs careful selection.


BACKGROUND
Funding for this study was provided by the Health Technology Assessment programme of the National Institute for Health Research.
Southampton Health Technology Assessments Centre, University of Southampton, Southampton, UK.
Emma
E
Loveman
Southampton Health Technology Assessments Centre, University of Southampton, Southampton, UK.
Jeremy
J
Jones
Southampton Health Technology Assessments Centre, University of Southampton, Southampton, UK.
Andrew J
AJ
Clegg
Southampton Health Technology Assessments Centre, University of Southampton, Southampton, UK.
Joanna
J
Picot
Southampton Health Technology Assessments Centre, University of Southampton, Southampton, UK.
Jillian L
JL
Colquitt
Southampton Health Technology Assessments Centre, University of Southampton, Southampton, UK.
Diana
D
Mendes
Department of Radiology, University Hospital Southampton, Southampton, UK.
David J
DJ
Breen
University of Southampton Clinical Trials Unit, University Hospital Southampton, Southampton, UK.
Emily
E
Moore
Public Health Sciences and Medical Statistics, University of Southampton Faculty of Medicine, University Hospital Southampton, Southampton, UK.
Steve
S
George
University of Liverpool, University Hospital Aintree, Liverpool, UK.
Graeme
G
Poston
Gastrointestinal Unit, Royal Marsden Hospital, London, UK.
David
D
Cunningham
Division of Surgical Oncology, the Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, the Netherlands.
Theo
T
Ruers
University Surgery, University of Southampton Faculty of Medicine, University Hospital Southampton, Southampton, UK.
John
J
Primrose
D055011:Ablation Techniques / Q000009:adverse effects / Q000191:economics* / Q000379:methods; D000368:Aged; D003362:Cost-Benefit Analysis; D018450:Disease Progression; D004621:Embolization, Therapeutic / Q000009:adverse effects / Q000191:economics* / Q000379:methods; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000191:economics / Q000556:secondary / Q000601:surgery / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D019057:Quality-Adjusted Life Years; D016019:Survival Analysis; D013997:Time Factors; D006113:United Kingdom