Liver cancer biopsy – back to the future?!

Abstract

Liver Cancer Biopsy -Back to the Future?! H epatocellular carcinoma (HCC) is the only major cancer in which diagnosis and subsequent indication for treatment is not regularly established by histology. Current AASLD and EASL guidelines do not require biopsy for tumors that develop in cirrhotic livers and in chronic hepatitis B, if the imaging results show changes interpreted as HCC. This leads to an estimated 60-70% of nonresectable liver tumors being treated as HCC without tissue confirmation. Originally seen as an achievement, this approach neglects basic oncological principles and has had unforeseen negative consequences for diagnosis and treatment. At a time when oncology is moving towards personalized medicine, the lack of tissue in a large proportion of cases has significantly limited this approach for HCC. The foundation of personalized medicine is an integrative molecularmorphological subtyping of tumors using predictive molecular testing and targeted therapies. Other tumor entities, such as non-small-cell lung cancer, breast cancer, and colorectal carcinoma, have all witnessed improved integrative diagnostics, a flourishing trial scenario, novel predictive tests, innovative therapies, and an active bench-bedside-bench research scenario. Not so for HCC. What are the reasons? While there are many, we believe reduced numbers of tumor biopsies has been critical.Correct classification and subtyping of tumors is the foundation for rational therapy and the current WHO classification is based on integrated molecular and morphological data. This smart move has improved overall tumor definition and other organ systems have benefited enormously from this concept by the establishment of defined subtypes that require different approaches in diagnostics, treatment, and trial design. However, the effect for HCC has been limited to date, not because HCC is fundamentally different from other solid tumors, but due to a lack of interdisciplinary coevolution of diagnostics, culminating in a greatly reduced number of diagnostic liver biopsies.HCC is best considered not as a homogenous entity but as a closely related group of morphologically and molecularly distinct cancer subtypes. As one example, fibrolamellar carcinoma is already a well-accepted morphological and molecular subtype of HCC 1 ; furthermore, approximately 4-5% of liver cancers show both clear cut hepatocellular and cholangiocellular differentiation and are classified as combined HCC/CC. 2 In both cases, subtyping is clinically relevant and only established by histology. The importance of tumor subtyping will certainly increase in the future: even within the category of more typical HCCs, relevant morphological/molecular subtypes can be discerned. The new chromophobe subtype shows a distinct morphology as well as a specific molecular mechanism to overcome replicative senescence (alternative lengthening of telomeres), in contrast to telomerase activation seen in most HCCs. 3 The molecular mechanisms behind other subtypes, such as steatohepatitic, scirrhotic, and...

Clinical implications of basic research in hepatocellular carcinoma

“…One of the main concerns with routine biopsy of all liver lesions is needle track seeding of the tumor, which has been reported at a low but variable frequency, with a large study of more than 1000 patients reporting a frequency of 0.76% (22) and a meta-analysis of 8 studies reporting it to be 2.7% (23). The other risk associated with liver biopsy is bleeding, but this risk is low at around 0.1-0.01% (24). Although the aforementioned risks are small they are not inconsequential.…”

“…The lack of biological tissue specimens from the majority of patients with HCCs will significantly impede this intermediate phase in the development of biomarkers for HCC and delay the advance towards personalized approaches to HCC management. While some experts argue that lack of known biomarkers and molecular subtypes makes routine biopsies of all HCC patients unethical (25) others argue that increasing the frequency of liver biopsies for HCC especially in clinical trial settings is crucial to identify biomarkers and advance the field of personalized targeted therapy for HCC (24). …”

Complete and Sustained Off-Therapy Response to Sorafenib in Advanced Hepatocellular Carcinoma

“…In this regard, the histological sample provides important and unique information that currently cannot be replaced by any other test, but the recent trend towards a reduction in HCC biopsies could represent a major obstacle to a personalized approach in liver cancer [12]. Perhaps we do need to take a step back in order to make one forward?…”

Postsorafenib systemic treatments for hepatocellular carcinoma: questions and opportunities after the regorafenib trial

“…On the contrary, obtaining samples from liver biopsies is more problematic and comes with risks of procedural complications. The opportunity of liver biopsies is a hot topic in hepatic oncology and has been recently object of a debate between eminent experts in the field [59,60]. The clinical and biological heterogeneity of patients with advanced HCC and the need for biomarkers will probably lead to a 'back to the future' scenario, with a predictable trend toward an increase in the number of liver biopsies in patients eligible for clinical trials [60].…”