Hepatocellular carcinoma in the United States. Lessons from a population-based study in Medicare recipients
Article Outline
The interest and research activity in diagnosis and treatment of hepatocellular carcinoma (HCC) has increased sharply over recent decades [1]. Twenty years ago, this cancer was seen as a disease almost entirely restricted to Asia and sub-Saharian Africa. It was equally assumed that early diagnosis was unfeasible, that treatment was not effective, that its prognosis was very poor with survival rarely exceeding 3 months. All these concepts are outdated. Several registries in Europe and America have shown that the incidence of HCC has experienced a significant increase over recent years and currently, HCC ranks among the five most important cancer killers worldwide [2]. Still, the majority of cases appear in Asia and sub-Saharian Africa, but HCC incidence is not negligible in most areas of the world.
As is commonly known, HCC appears in most cases within a chronically diseased liver, the most frequent etiologic agents being hepatitis B and C viruses and excessive alcohol intake. Interestingly, modern cohort studies have shown that HCC is now the leading cause of death in patients with cirrhosis [3], [4], [5]. Hence, all hepatologists and healthcare providers involved in the management of patients with liver disease are now aware of the increased risk of cancer of their patients. Simultaneously, major effort and importance is placed in developing guidelines and protocols to deliver optimal healthcare to patients with either suspected or proven HCC. Years ago, the European Association for the Study of Liver Disease (EASL) organised the Barcelona Monothematic Conference, where a panel of experts produced the first Western document to guide the diagnosis and treatment of patients with HCC [6]. The American Association for the Study of Liver Diseases (AASLD) has recently published the Practice Guidelines for the Management of HCC [7] and in the following months a new document prepared by a panel of experts of EASL, AASLD and the Japan Society of Hepatology that met at the second Barcelona meeting on HCC will further homogenise the management and research needs on a more worldwide level.
These comments are relevant to frame the value and message of the study by the group of El-Serag published in this issue of the Journal [8]. This team has played a major role in the definition of the importance of HCC in the United States and the specific epidemiological profile in their country. Their data have unequivocally depicted the increase in the incidence of HCC (which has almost doubled in the last 30 years) [9] and through the analysis of large databases they have emphasised the role of viral infection, alcoholism, diabetes and HIV [10], [11], [12]. The new study further digs into the databases and tries to assess to what extent the management of the HCC patients is adequate and/or homogeneous and whether the outcome of the patients fits into the expected figures. The results should represent a concern for the authority responsible of health care delivery to HCC patients within Medicare. There is significant heterogeneity in the type of treatment offered and in some instances the therapy applied does not adhere to the most recent state of the art recommendations. In addition, the survival registered in the database does not reproduce the findings of modern cohort studies in which treatment allocation is decided following a proper algorithm. El-Serag et al. show that only 11% of the potential candidates for transplantation were actually transplanted; that just 13% patients for surgical resection received such therapy and, finally, that only 14% of those apparently fit for local ablation were treated. By contrast, 19% of patients with HCC lesions >10
cm and 5% of patients with metastatic disease underwent therapies with curative intent, while in most referral Units they would have been dismissed because of the well-known poor outcome [8]. As a whole, it appears that some individuals who could have benefited from therapy were not treated and some who were treated would have been better served if they had been left untreated.
Obviously, all this rough interpretation should be tempered because of the database limitations. The most important of them is the fact that the database represents a non-random segment of the population, whose healthcare is provided by Medicare. Furthermore, the database allows to extract a general view of the situation regarding HCC management, but the data collected to construct the database does not allow to perform an in depth analysis to clarify why treatments were not offered in some instances or why they were apparently indicated in a controversial strategy. The retrospective analysis of the database cannot ensure a proper diagnosis and staging of the patients and obviously these critical points in clinical decision making were largely heterogeneous among centres. Furthermore, significant co-morbidity cannot be accurately established and this may be the most important reason to avoid therapy. The authors have used an index to estimate presence of co-morbidities, but even with this approach, the reason why treatment was offered or denied is impossible to be ascertained. Intriguingly enough, the authors show that there are also major differences according to the location of the patients. This means that the treatment strategy is not the same all over the US, but the difference may also be the result of some specific cultural or economic profile of the population attended by Medicare in different states.
It could be argued that population based studies assessing incidence, treatment allocation and survival are not available. Hence, the study by El-Serag et al. may reflect real life while cohort studies raised in referral Units merely report the cases in best conditions that are evaluated in these specific Centres. While this could be partially the case in the provision of treatment and for overall survival, the argument cannot be used to explain the outcome after therapies. Current data applying adequate criteria indicate that survival after resection, transplant or percutaneous ablation should definitely exceed 50% at 3 years [7] and here we are given figures that are far below these limits. Median survival after transplantation is approximately less than 4 years, and does not reach 3 years after surgical resection. Similarly, median survival after percutaneous ablation and transarterial chemoembolization does not reach 2 and 1 year, respectively.
Do these comments suggest that the study by El-Serag et al. has no value? Not at all! It is clear that HCC is an emerging health problem that has not been adequately dealt with in several countries. The present study indicates that this is also true at least in some specific populations within the US. This critical information should be the trigger to set up the strategy to further assess the gaps between state of the art knowledge and its application in real life. Both EASL and AASLD have made the effort to offer health care providers with guidelines to deliver optimal care [6], [7]. Furthermore, the management and research in the US has been the focus of specific conferences organised by AASLD and NIH, that have prompted that liver cancer is now one of the targets of a major research funding within the NIH action plan of the liver disease section. This research activity both in the experimental laboratory and in the clinical setting should be instrumental to face the HCC ‘epidemic’ with proper cost-efficiency. In that sense, it has to be stressed that the economic burden of HCC management is not negligible. A recent analysis by Kim et al. [13] has shown that the clinical activity related to HCC management has markedly increased in the past 20 years and that this has a direct translation in costs. According to these authors, the hospitalisation of HCC patients in the US during the year 2000 may have had a cost of $509 million, a figure that is compatible with the estimate made by the American Gastroenterological Association, that calculated all the costs associated with HCC in 1998 to be $998 million [13].
In summary, while great improvements have been achieved in the awareness of the relevance of HCC and its increasing incidence, there is still a major need to improve all the aspects related to its diagnosis and management. Probably, Japan and Europe are ahead of the US because the increase in HCC incidence occurred earlier in these countries and thus, the need to have the proper resources in place was a necessity years before. Now, the problem has unequivocally emerged in the US and the study by El-Serag et al. shows that the healthcare delivery to HCC patients within Medicare is not optimal. There is major room for improvement and this will certainly take place in the next few years.
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PII: S0168-8278(05)00692-6
doi:10.1016/j.jhep.2005.11.001
© 2005 European Association for the Study of the Liver. Published by Elsevier Inc. All rights reserved.
