Radiofrequency ablation or resection for small colorectal liver metastases - a plea for caution.

Abstract

Colorectal cancer (CRC) is among the leading causes for cancer death worldwide (1) and remains a serious problem for the public healthcare systems due to continuously growing costs of the treatment, and relatively low cure rates, especially in advanced stages of disease. The liver is secondary only to lymph nodes as a site for metastasis from primary CRC - about 50% of the patients developed liver metastases (CLM) during their course of disease, and in approximately ¾ of these the liver is the only site of distant spread (2). To date, resection of the metastases (LR) is the only proven potentially curative treatment option for the patients with CLM. However, despite the current advances in the concepts and techniques in liver surgery, the vast majority of the patients with CLM as well as those with other liver malignancies are not amenable to curative surgery. There is a growing need for efficient and minimally invasive techniques for the treatment of unresectable primary and metastatic liver cancer. In these circumstances several liver-directed local treatment modalities were developed and intensively explored during the years, with the aim to achieve local control, initially in patients with unresectable liver tumors, and eventually to compare further the results with those of hepatic resection. Among these local treatment options, the radiofrequency ablation (RFA) has become most popular and widely accepted local ablation modality during the past two decades. The accumulated evidence from several studies, including randomized trials, proved the safety and efficacy of RFA in the treatment of patients with hepatocellular carcinoma on cirrhosis (HCC) and even the superiority of RFA over hepatic resection in some subgroups of patients with HCC (3). None of these evidences can be directly applied to the patients with CLM. The benefit from RFA for the patients with unresectable CLM in terms of prolonged progression-free survival (PFS) can be regarded as proven by several nonrandomized and one randomized study - EORTC 40004 (4). In the latter, RFA plus systemic chemotherapy are compared with systemic treatment alone. The median overall survival (OS), 30-month OS, and PFS are respectively 45.3 months, 61.7% and 16.8 months for the combined treatment vs. 40.5 months, 57.6% and 9.9 months for systemic treatment group. The EORTC 40004 does not demonstrate OS advantage from RFA and all non-randomized studies which demonstrate the OS benefit from adding RFA to systemic treatment have used historical and/or not well matched control groups. There is no any prospective, randomized trial comparing the efficacy of RFA with that of LR for CLM currently available. The literature data suggests that if local control is achieved by RFA as a sole procedure or as an adjunct to LR, the combination with current systemic therapy can reflect in prolonged OS compared to chemotherapy alone (5). Some authors go further ahead and propose RFA as a first-line treatment for the patients with resectable CLM, in order to “spare” patients from “unnecessary” LR if local control is achieved by RFA (6,7), however they have been criticized by several arguments (8,9). Recently Solbiati et al. (10) reports the long-term results of the treatment of small CLM with percutaneous RFA plus irinotecan- or oxaliplatin-based systemic therapy. This report includes 99 patients with minimum of 3 years follow-up. No patient has had liver dysfunction or poor performance status and has been included in the study because of ineligibility (80.1%) or refusal (19.9%) of LR. The vast majority of the patients in this report - 73.7% have had one or two CLM, and the mean size of metastases has