October 21, 2021
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Hepatocellular carcinoma: Hope on the horizon

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This month’s cover story highlights the growing burden of hepatocellular carcinoma, the most common type of primary liver cancer, in the United States. Despite being a cancer that does not typically receive much attention, HCC is projected to become the third leading cause of cancer-related death in the United States by 2040 if current trends continue. Its increasing mortality is related to a growing number of cases in the setting of non-alcoholic fatty liver disease, the liver manifestation of the metabolic syndrome, and a high proportion of HCC cases being detected at a late stage. While patients detected at an early stage are amenable to curative therapies such as liver transplantation and have a median survival exceeding 5 years, those diagnosed at a late stage traditionally have had limited therapeutic options and a median survival of only 1 year.

Increase Early HCC Detection

Given the stark difference in prognosis between early-stage and late-stage HCC, aggressive efforts to increase early HCC detection is likely one of the most important strategies to reduce HCC mortality. Therefore, professional societies, including the American Association for the Study of Liver Diseases, recommend HCC screening in at-risk patients, including those with cirrhosis. Several studies have highlighted the strong association between HCC screening and improved early HCC detection, curative treatment and reduced HCC-related mortality. Abdominal ultrasound, with or without a serum biomarker alpha-fetoprotein, has served as the cornerstone of HCC screening for decades; however, its effectiveness is limited by poor sensitivity for early-stage HCC and underuse in clinical practice. Recently, there has been tremendous progress in identifying novel blood-based biomarkers and alternative imaging modalities, which appear to have higher sensitivity for early-stage HCC and should be easier to apply in clinical practice. Although these strategies still require validation, in parallel, studies have highlighted the benefit of interventions, such as best practice alerts or population-based outreach programs, to improve HCC screening implementation.

Source: Adobe Stock.
Source: Adobe Stock.

Therapeutic Revolution

Amit G. Singal, MD, MS
Amit G. Singal

As a transplant hepatologist who serves as medical director of the multidisciplinary Liver Tumor Program at the University of Texas Southwestern Medical Center, I have also witnessed first-hand how advances in HCC therapeutic options have improved patient outcomes and prognosis. Over the last few years, we have seen expanded patient eligibility for curative therapies including liver transplantation and surgical resection, increased experience with safe delivery of internal and external radiation-based therapies that can induce objective responses in a high proportion of patients, and an explosion of available systemic therapy options for patients with advanced stage HCC. Further, I believe we are only at the beginning of the therapeutic revolution for HCC management, with several ongoing trials evaluating the combination of immune checkpoint inhibitors with other therapies in patients with earlier stages of disease.

Reducing Disparities

However, there are still several challenges that require attention. First, HCC is a disease that disproportionately impacts racial and ethnic minorities and persons of low socioeconomic status, and interventions targeted to these populations are needed to reduce disparities. Second, more than 90% of patients with HCC have underlying liver disease, many of whom present with advanced liver dysfunction precluding aggressive HCC therapy. However, these patients are excluded from most clinical trials, so therapies that are proven safe and effective in this sizable portion of patients with HCC are urgently needed.

Finally, many proven strategies are underused in clinical practice – including HCC screening in at-risk individuals and curative treatments in patients with early-stage HCC – contributing to HCC poor prognosis. Continued efforts are needed to ensure improved HCC screening and treatment strategies are consistently delivered to our patients if we hope to reverse current trends and reduce HCC mortality in the future. If we work together to tackle these issues, I remain optimistic about the future of HCC.