Local recurrence rates after radiofrequency ablation or resection of colorectal liver metastases. Analysis of the European Organisation for Research and Treatment of Cancer #40004 and #40983

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Abstract

Aim

The aim of this study is to describe local tumour control after radiofrequency ablation (RFA) and surgical resection (RES) of colorectal liver metastases (CLM) in two independent European Organisations for Research and Treatment of Cancer (EORTC) studies.

Background

Only 10–20% of patients with newly diagnosed CLM are eligible for curative RES. RFA has found a place in daily practice for unresectable CLM. There are no prospective trials comparing RFA to RES for resectable CLM.

Methods

The CLOCC trial randomised 119 patients with unresectable CLM between RFA (±RES) + adjuvant FOLFOX (±bevacizumab) versus FOLFOX (±bevacizumab) alone. The EPOC trial randomised 364 patients with resectable CLM between RES ± perioperative FOLFOX. We describe the local control of resected patients with lesions ⩽4 cm in the perioperative chemotherapy arm of the EPOC trial (N = 81) and the RFA arm of the CLOCC trial (N = 55).

Results

Local recurrence (LR) rate for RES was 7.4% per patient and 5.5% per lesion. LR rate for RFA was 14.5% per patient and 6.0% per lesion. When lesion size was limited to 30 mm, LR rate for RFA lesions was 2.9% per lesion. Non-local hepatic recurrences were more often observed in RFA patients than in RES patients, 30.9% and 22.3% respectively. Patients receiving RFA had a more advanced disease.

Conclusions

LR rate after RFA for lesions with a limited size is low. The local control per lesion does not appear to differ greatly between RFA and surgical resection. This study supports the local control of RFA in patients with limited liver metastases. Future studies should evaluate in which patients RFA could be an equal alternative to liver resection.

Introduction

Colorectal cancer remains the most common cancer and with 212.000 deaths per year, the second most frequent cancer related cause of death in Europe [1], [2]. When diagnosed with colorectal cancer, up to half of the patients develop liver metastases (CLM). In these patients surgical resection of the liver metastases is the procedure of choice with five-year survival rates up to 60% [3], [4]. However, surgical resection is only feasible in approximately 10–20% of the cases. In the majority of patients, too extensive liver disease, extra-hepatic disease or co-morbidity preclude radical resection.

Non-surgical alternatives have been introduced to treat these patients with unresectable colorectal liver metastases. Among these alternative treatments, radiofrequency ablation (RFA) is most frequently used. In a randomised phase II study (CLOCC) on patients with unresectable colorectal liver metastases, median overall survival was 45.3 months for RFA plus systemic treatment versus 40.5 months for systemic treatment only (p = 0.22). PFS rate at 3 years for combined treatment was 27.6% compared to 10.6% for systemic treatment only (p = 0.025) [5]. Although the effect of RFA treatment on PFS was significant, compelling evidence on the effect of local tumour ablation on overall survival is still lacking. Nevertheless, RFA has been accepted in the surgical and radiological community as an attractive treatment modality in patients with unresectable colorectal liver metastases.

In patients with resectable colorectal liver metastases resection (RES) is considered the treatment of choice. RFA is only considered an alternative in patients unfit for surgical resection, mainly because high local recurrence rates were observed in several studies on unresectable CLM [6], [7]. In early series, local recurrence rates of up to 46% have been reported after RFA. Next generation probes, better imaging by computed tomography (CT)-guided procedures, increased experience and better patient selection all have improved local recurrence rates after RFA to 5.2–8.8% [8], [9], [10]. Such figures suggest that RFA could be an alternative to resection in a selected group of patients.

The best way to determine the potential indications of RFA in patients with curable CLM would be to compare these two procedures in a prospective randomised phase III trial. An attempt to organise such a trial has failed (French FFCD 2002-02) and it is unlikely that another study can be organised in the near future. The European Organisation for Research and Treatment of Cancer (EORTC) has conducted two randomised controlled trials on patients with colorectal liver metastases; study 40983 (EPOC) comparing perioperative chemotherapy to surgery alone in resectable colorectal liver metastases and study 40004 (CLOCC) comparing RFA (±RES) plus systemic therapy versus systemic therapy alone in patients with unresectable colorectal liver metastases. The aim of the present study is to describe the local control rate of resection and RFA within the controlled setting of these two independent EORTC studies.

Section snippets

Materials and methods

Data were reviewed from patients included into two clinical trials performed by the European Organisation for Research and Treatment of Cancer (EORTC), concerning colorectal liver metastases.

Study 40004, also known as the CLOCC trial [11], compared patients with unresectable colorectal liver metastases treated by RFA (with or without additional resection of resectable lesions) plus adjuvant systemic therapy to systemic therapy alone (FOLFOX ± bevacizumab). In both arms systemic treatment was

Patient and tumour characteristics

Table 1 shows the baseline characteristics of the selected patients from the CLOCC and EPOC trial (resp. 55 and 81 patients). Clinical parameters, such as age, sex, World Health Organisation (WHO) performance score and the location of the primary cancer, were similar between the two patient groups.

Tumour characteristics were different between the two groups. Median number of metastases for the RFA patients was 4.0 (range 1–9) compared to 1 (range 1–4) for the RES patients. Of the resected

Discussion

Local recurrence rate on a lesion basis was 6% and 5.5% resp. after RFA and RES (combined with systemic therapy). The overall local recurrence rate was 14.5% in patients with CLM treated by RFA and 7.4% in patients with CLM treated by resection. The median number of metastases per patient was higher in the RFA study.

Median time to local recurrence was 356 days after RFA and 412.5 days after resection, follow-up was longer after resection than after RFA (8.2 versus 4.7 years). Follow-up methods in

Conflict of interest statement

None declared.

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Support and grants: This publication was supported by a donation from the Kankerbestrijding/KWF from The Netherlands through the EORTC Charitable Trust.

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