Thermal ablation in colorectal liver metastases: Lack of evidence or lack of capability to prove the evidence?

Many studies suggest that combined multimodality treatments including ablative therapies may achieve better outcomes than systemic chemotherapy alone in patients with colorectal liver metastases. Nevertheless,ablative therapies are not yet considered as effective options because their efficacy has never been proved by randomized controlled trials(RCT). However, there are in literature no trials that failed in demonstrating the effectiveness of ablative treatments: what are lacking, are the trials. All the attempts to organize phase Ⅲ studies on this topic failed as a result of non accrual. Just one prospective RCT comparing radiofrequency ablation combined with systemic chemotherapy vs chemotherapy alone has been published. It was designed as a phase Ⅲ study, but it was closed early because of slow accrual, and was downscaled to phase Ⅱ study, with the consequent limits in drawing definite conclusions on the benefit of combined treatment. However, the combination treatment met the primary end point of the study and obtained a significantly higher 3-year progression-free survival than systemic chemotherapy alone. It is very unlikely that ultimate efficacy of ablation treatments will ever be tested again, and the best available evidence points toward a benefit for the combination strategy using ablative treatments and chemotherapy.