TACE treatment in hepatocellular carcinoma: what should we do now?

TACE treatment in hepatocellular carcinoma: What should we do now? Fabio Farinati, , Anna Giacomin, Veronica Vanin Department of Surgical and Gastroenterological Sciences, Section of Gastroenterology, University of Padova, Padova, Italy For the ITA.LI.CA (Italian Liver Cancer) group To the Editor: We read with much interest the comment by Forner et al.[1] on the recently published Cochrane review on Transcatheter Arterial (Chemo) Embolization (TACE/TAE) treatment in hepatocellular carcinoma by Oliveri et al.[2]. The debate on the effectiveness of TACE in patients with intermediate stage hepatocellular carcinoma (HCC) is still open, indeed. On the one hand, as summarized in the updated American Association for the Study of Liver Diseases (AASLD) guidelines, there is no doubt that the level of evidence on the efficacy of TACE in the treatment of intermediate stage HCC is strong (IA, according to the standard evaluation [3], with a consequently strong grade of recommendation [Grade A]). On the other hand, there is also no doubt that this strength lies basically on the results of two randomized prospective studies [4] and [5] that deeply condition the two meta-analyses published on the topic [6] and [7]. Nevertheless, TACE is also supported by the fact that it is used in the everyday clinical practice of every center involved in the management of HCC, a very low level (IV), but still important, evidence. Dr. Forner correctly underlines that one of the papers quoted in Olivieri’s meta-analysis, the Doffoel’s randomized prospective trial of TACE vs. tamoxifen [8], presents many biases and includes patients that may have been “sub-optimally staged, selected and/or treated”. In several French studies, indeed (see also the two Pelletier’s articles [9] and [10]), the survival after TACE is so short that being affected by an intermediate stage HCC in France at the end of the last century would have suggested to move to other countries for treatment. Indeed, the reported 1-year survival (ranging from 25% to 50%) was not considered acceptable elsewhere and in past years those two studies heavily conditioned the clinical evaluation of TACE as a treatment for patients with multinodular HCC. The Cochrane review in any case casts new doubts on the topic, doubts that induce to wonder what to do in patients with intermediate stage HCC, if one accepts the conclusions of the review. In our experience, based on the data (prospectively collected over 20 years) of the ITA.LI.CA database, patients with intermediate stage HCC treated by TACE present a median survival of 35 months (42 months in those treated in the last decade), with 1- and 5-year survivals of 80% and 18%, respectively. Having said this, it is worth noting that only a fraction of patients with an intermediate stage HCC were treated by TACE, while in the other cases, the treatment options vary from surgery or percutaneous treatments to best supportive care, depending on a number of factors not considered in the Barcelona Clinic Liver Cancer (BCLC) algorithm, such as age, co-morbidities, patient’s decision, and local expertise, particularly, as far as the availability of highly experienced surgical teams is concerned. Interestingly enough, patients with intermediate stage HCC who can be treated more aggressively tend to survive longer than those treated by TACE (median survival of 52 months and 5-year survival over 30%). Our, still unpublished, data clearly demonstrate that TACE should not be abandoned, remaining the standard of care, in clinical practice, for most patients with intermediate stage HCC. However, the indication to TACE should not be automatic and, if the patients are considered eligible for more aggressive treatments, in a multidisciplinary approach also including percutaneous ablation and surgery, an even better survival can be obtained. Nowadays, there is indication for a combined/sequential tailored treatment, with a strategy that involves hepatologists, interventional radiologists, and surgeons. Likely, in the near future an adjuvant treatment with sorafenib or new anti-angiogenetic molecules will be part of this strategy.