Should radiofrequency ablation be used in patients with liver colorectal metastases? 

Colorectal cancer is one of the most common malignant tumour worldwide and approximately 50 % of patients will develop liver metastases (liver is the first site of metastatic disease). Hepatic resection is the only curative option, but only 15-20% of patients with liver metastases from colorectal cancer are suitable for surgical standard treatment. Besides chemotherapy, several minimally invasive treatment techniques have been developed to treat patients with CRLMs: hepatic arterial infusion, cryotherapy, microwave ablation, selective internal radion treatment, radiofrequency ablation. During the past decade radiofrequency ablation has superseded other ablative therapies, due to its low morbidity, mortality, safety and patient acceptability. Radiofrequency ablation is a minimally invasive technique in which a needle is inserted into the tumour (liver metastases) either getting access by way of the skin (percutaneously) or via open approach (surgically). Alternating current is generated using radio waves and, through needle, create local tissue temperatures of 50-100˚C temperature, that causes “coagulation” and tumour necrosis. According to several studies RFA is technically feasible and safe for the treatment of CRLMs, however little is known about its efficacy in terms of overall survival (OS), disease free survival (DFS) and local recurrence. The aim of this review was to see if the treatment of CRLMs with RFA provides more benefit in terms of overall survival, disease free survival and local recurrence. This review include 18 studies (10 observational studies, 7 CCTs and an additional 1 RCT) comparing radiofrequency ablation with any other treatment. The heterogeneity regarding interventions, comparisons and outcomes rendered the data unusable and unsuitable for drawing conclusions. There is insufficient evidence to recommend the use of radiofrequency ablation for a radical treatment of liver metastases from colorectal cancer. High quality randomised clinical trials are required to answer on the potential benefit and harms associated with the use of radiofrequency ablation in the treatment of liver metastases from colorectal cancer.

Authors' conclusions: 

This systematic review gathers information from several controlled clinical trials and observational studies which are vulnerable to different types of bias. The imbalance between characteristics of patients in the allocated groups appears to be the main concern. Only one randomised clinical trial (published as an abstract), comparing 60 patients receiving RFA plus CT versus 59 patients receiving CT alone, was identified. This study showed that PFS was significantly higher in the group that received RFA. However, it was not able to provide information on overall survival. In conclusion, evidence from the included studies are insufficient to recommend RFA for a radical oncological treatment of CRLMs.

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Background: 

Colorectal cancer (CRC) is the most common malignant tumour and the third leading cause of cancer deaths in USA. For advanced CRC, the liver is the first site of metastatic disease; approximately 50 % of patients with CRC will develop liver metastases either synchronously or metachronously within 2 years after primary diagnosis. Hepatic resection (HR) is the only curative option, but only 15-20% of patients with liver metastases from CRC (CRLMs) are suitable for surgical standard treatment. In patients with unresectable CRLMs downsizing chemotherapy can improve resectability (16%). Modern systemic chemotherapy represents the only significant treatment for unresectable CRLMs. However several loco-regional treatments have been developed: hepatic arterial infusion (HAI), cryosurgical ablation (CSA), radiofrequency ablation (RFA), microwave ablation and selective internal radion treatment (SIRT). During the past decade RFA has superseded other ablative therapies, due to its low morbidity, mortality, safety and patient acceptability.

Objectives: 

The objective of this study was to systematically review the role of radiofrequency ablation (RFA) in the treatment of CRLMs.

Search strategy: 

We performed electronic searches in the following databases:CENTRAL, MEDLINE and EMBASE. Current trials were identified through the Internet using the Clinical-Trials.gov site (to January 2, 2012) and ASCO Proceedings. The reference lists of identified trials were reviewed for additional studies.

Selection criteria: 

Randomized clinical trials (RCTs), quasi-randomised or controlled clinical trials (CCTs) comparing RFA to any other therapy for CRLMs were included. Observational study designs including comparative cohort studies comparing RFA to another intervention, single arm cohort studies or case control studies have been included if they have: prospectively collected data, ten or more patients; and have a mean or median follow-up time of 24 months. Patients with CRLMs who have no contraindications for RFA. Patients with unresectable extra-hepatic disease were also included.Trials have been considered regardless of language of origin.

Data collection and analysis: 

A total of 1144 records were identified through the above electronic searching. We included 18 studies: 10 observational studies, 7 Clinical Controlled Trials (CCTs) and an additional 1 Randomized Clinical Trial (RCT) (abstract) identified by hand searching in the 2010 ASCO Annual Meeting. The most appropriate way of summarizing time-to-event data is to use methods of survival analysis and express the intervention effect as a hazard ratio. In the included studies these outcome are mostly reported as dichotomous data so we should have asked authors research data for each participant and perform Individual Patient Data (IPD) meta-analysis. Given the study design and low quality of included studies we decided to give up and not to summarize these data.

Main results: 

Seventeen studies were not randomised and this increases the potential for selection bias. In addition, there was imbalance in the baseline characteristics of the participants included in all studies. All studies were classified as having a elevate risk of bias. The assessment of methodological quality of all non-randomized studies included in meta-analysis performed by the STROBE checklist has allowed us to identify several methodological limits in most of the analysed studies. At present, the information from the single RCT included (Ruers 2010) comes from an abstract of 2010 ASCO Annual Meeting where the allocation concealment was not reported; however in original protocol allocation concealment was adequately reported (EORTC 40004 protocol). The heterogeneity regarding interventions, comparisons and outcomes rendered the data not suitable.

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