“Wait and see” policy for early hepatocellular carcinoma
Authors: Giampiero Francica, Ilario de Sio, Maurizio Pompili, Tito Livraghi
Journal: Journal of Hepatology (2013)

Marginal survival benefit in the treatment of early hepatocellular carcinomaJournal of HepatologyVol. 58Issue 2PreviewEarly treatment has been recommended for hepatocellular carcinoma (HCC) due to its high cure rate. However, the reported survival benefits of treating early HCC may be affected by lead time. Full-Text PDF Reply to: ““Wait and see” policy for early hepatocellular carcinoma”Journal of HepatologyVol. 59Issue 3PreviewIs early hepatocellular carcinoma (HCC) really a life-threatening disease? Full-Text PDF Open Access We would like to comment on the recent article by Midorikawa and colleagues [[1]Midorikawa Y. Takayama T. Shimada K. Nakayama H. Higaki T. Moriguchi M. et al.Marginal survival benefit in the treatment of early hepatocellular carcinoma.J Hepatol. 2013; 58: 306-311Abstract Full Text Full Text PDF PubMed Scopus (51) Google Scholar] about the management of early hepatocellular carcinoma (HCC). The authors suggest a “wait and see” policy when these lesions are recognized in a cirrhotic liver since the difference between the benefit of resection and observation was negligible in this subgroup of patients. In the authors’ opinion, only overt HCC should be promptly treated whereas early HCC lesions should not be submitted to any form of therapy (including liver resection and percutaneous ablation) because of the treatment-related risks of liver function damage and severe complications. This clinical scenario parallels that of prostate cancer (PC): as it happens for small HCC detected during surveillance programs, more and more small volume tumoral foci are detected on prostatic biopsy ensuing Prostate Specific Antigen (PSA) screening [[2]Heidenreich A. Bellmunt J. Bolla M. Joniau S. Mason M. Matveev V. et al.EAU guidelines on prostate cancer. Part 1: screening, diagnosis, and treatment of clinically localised disease.Eur Urol. 2011; 59: 61-71Abstract Full Text Full Text PDF PubMed Scopus (1264) Google Scholar]. Nowadays, deferred treatment in patients with insignificant disease has been advocated in the belief that radical prostatectomy is associated with significant morbidity and decrease in the quality of life whereas the majority of men are not at risk for dying of the disease, and that those who demonstrate disease progression can be identified and treated before the tumor becomes incurable [[2]Heidenreich A. Bellmunt J. Bolla M. Joniau S. Mason M. Matveev V. et al.EAU guidelines on prostate cancer. Part 1: screening, diagnosis, and treatment of clinically localised disease.Eur Urol. 2011; 59: 61-71Abstract Full Text Full Text PDF PubMed Scopus (1264) Google Scholar]. As a consequence, over the last decade, active surveillance programs have gained popularity: in suitable candidates, stringent follow-up protocols including repeat biopsy are implemented so as to pick-up early tumoral progression [[3]Dall’Era M.A. Albertsen P.C. Bangma C. Carroll P.R. Carter H.B. Cooperberg M.R. et al.Active surveillance for prostate cancer: a systematic review of the literature.Eur Urol. 2012; 62: 976-983Abstract Full Text Full Text PDF PubMed Scopus (489) Google Scholar]. However, similarities between HCC and PC clinical scenarios end at this point: the two tumors have different natural histories HCC carrying the worse prognosis and being superimposed on a chronic disease, which per se affects both patients’ outcome and the decision as to whether or not to start a whatsoever form of treatment. This makes the window for curative therapy much narrower than in patients with PC. We agree that surgery (including resection and liver transplantation) represents an undue and costly overtreatment for an early HCC, but the same is not true for radiofrequency ablation (RFA). In our opinion, the Midorikawa’s suggestion cannot be entirely shared since it relies on a misconception that surgery and local ablation are equivalent in terms of complications rate and capability of damaging liver function. To support their assumption they quote outdated and questionable references. In particular, the authors cite the article by Llovet et al. [[4]Llovet J.M. Vilana R. Bru C. Bianchi L. Salmeron J.M. Boix L. et al.Increased risk of tumor seeding after percutaneous radiofrequency ablation for single hepatocellular carcinoma.Hepatology. 2001; 33: 1124-1129Crossref PubMed Scopus (684) Google Scholar] where an exceedingly high rate of neoplastic seeding after RFA was reported. Those results, however, have been harshly criticized and a subsequent multicenter survey demonstrated clearly that, using a correct needle withdrawal technique, the seeding rate was far lower (less than 0.9% out of 1314 patients) and negatively affected only by a previous biopsy on the treated HCC nodule [[5]Livraghi T. Lazzaroni S. Meloni F. Solbiati L. Risk of tumour seeding after percutaneous radiofrequency ablation for hepatocellular carcinoma.Br J Surg. 2005; 92: 856-858Crossref PubMed Scopus (157) Google Scholar]. The authors seem to ignore that the worldwide use of RFA for HCC depends especially on its high efficacy in local control of the disease and lower invasiveness and costs when compared to surgery. In addition, there is recent evidence that RFA and resection offer similar results in terms of overall survival in case of HCC up to 3 cm emerging in well compensated cirrhosis [6Cho Y.K. Kim J.K. Kim W.T. Chung J.W. Hepatic resection versus radiofrequency ablation for very early stage hepatocellular carcinoma: a Markov model analysis.Hepatology. 2010; 51: 1284-1290Crossref PubMed Scopus (198) Google Scholar, 7Feng K. Yan J. Li X. Xia F. Ma K. Wang S. et al.A randomized controlled trial of radiofrequency ablation and surgical resection in the treatment of small hepatocellular carcinoma.J Hepatol. 2012; 57: 794-802Abstract Full Text Full Text PDF PubMed Scopus (570) Google Scholar]. One more drawback of an attendant approach for early HCC is that leaving a patients with an untreated cancer (even if small) poses other kinds of problems. Back to the parallelism with PC, the active surveillance is accepted by patients with reluctance as it is demonstrated by the low rate of enrollment in such protocols (not more than 30% of the suitable candidates) [[2]Heidenreich A. Bellmunt J. Bolla M. Joniau S. Mason M. Matveev V. et al.EAU guidelines on prostate cancer. Part 1: screening, diagnosis, and treatment of clinically localised disease.Eur Urol. 2011; 59: 61-71Abstract Full Text Full Text PDF PubMed Scopus (1264) Google Scholar]. Several reasons can explain this finding: the inability to predict with absolute certainty favorable from unfavorable disease on an individual basis, the poor predictive markers of progression, and finally the difficulty of modifying the established standards of care. All these factors, including the psychological attitude of patients and the loss of the opportunity for cure during the surveillance period, should be taken into account in case of an active surveillance protocol for early HCC as suggested by Midorikawa et al. It is not surprising that some urological groups are trying to apply the concept of local ablation in low-risk PC patients [[8]Lindner U. Trachtenberg J. Lawrentschuk N. Focal therapy in prostate cancer: modalities, findings and future considerations.Nat Rev Urol. 2010; 7: 562-567Crossref PubMed Scopus (95) Google Scholar]. Local therapy might prove to be the middle ground for this subgroup of men, by combining acceptable cancer treatment with low morbidity. If one considers the high rate of effectiveness in destroying HCC lesions up to 3 cm with low morbidity and no mortality [9Livraghi T. Meloni F. Di Stasi M. Rolle E. Solbiati L. Tinelli C. et al.Sustained complete response and complications rates after radiofrequency ablation of very early hepatocellular carcinoma in cirrhosis: is resection still the treatment of choice?.Hepatology. 2008; 47: 82-89Crossref PubMed Scopus (922) Google Scholar, 10Francica G. Saviano A. De Sio I. De Matthaeis N. Brunello F. Cantamessa A. et al.Long-term effectiveness of radiofrequency ablation for solitary small hepatocellular carcinoma: a retrospective analysis of 363 patients.Dig Liver Dis. 2013; 45: 336-341Abstract Full Text Full Text PDF PubMed Scopus (35) Google Scholar], then RFA is the ideal technique to eradicate a small tumoral focus (early HCC), minimizing the risk associated with expectant management. Thanks to the large experience in local ablation of liver cancer accumulated over the last three decades, all among hepatologists, gastroenterologists, and radiologists involved in the management of patients with HCC, seem to be far ahead along the way urologists are tempting to pursue. We think that a step backward is not warranted at this time. The authors declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript.