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As the most common type of primary liver cancer, hepatocellular carcinoma (HCC) continues to present a significant challenge for oncologists. In fact, HCC is the third-leading cause of cancer-related deaths worldwide and seventh in the United States.

And while advancements have been made in treatment options, there remain crucial unmet needs. That’s why we’re exploring these needs and promising avenues for improving the diagnosis and treatment of HCC.

Starting with Screening

Screening patients with risk factors for HCC has demonstrated reduction of mortality. Known risk factors associated with HCC have genetic, viral, and substance use origins, among others. Screening includes an alpha fetoprotein (AFP) blood test and a routine ultrasound screening every six months.

Yet only 24.7 percent of patients at high risk of HCC receive regular outpatient care, which includes screening. Nearly half (49.6%) of these failures occurred in patients known to have cirrhosis, which is a major risk factor for HCC.

Early Detection

HCC is often diagnosed at an advanced stage, limiting treatment options and survival rates. For some of these patients, not only is access to healthcare and screening a barrier, but early detection is also a challenge.

HCC is typically diagnosed through imaging, serum biomarkers, and/or biopsy. The gold standard method to diagnose HCC is liver biopsies, an invasive procedure with potential complications. While imaging is non-invasive and helpful, the sensitivity of these detection methods is complicated and remains low, ranging between 51.7 to 61.7 percent.

Currently, AFP is the primary biomarker used in conjunction with ultrasound to screen for HCC. Unfortunately, this approach lacks both sensitivity and specificity to be used as a diagnostic test alone. That’s why developing more sensitive and specific non-invasive techniques and biomarkers for early detection is paramount.

Risk Stratification: Optimizing Patient Management

Identifying patients at high risk for HCC progression is vital for prioritizing surveillance and early intervention. Collectively, current methods rely on specialist expertise to interpret clinical assessments, including factors like liver function and tumor size, and so more precise stratification tools are needed.

But by identifying patterns associated with early-stage HCC, this could aid in risk stratification and facilitate early detection, personalizing the management of patients with chronic liver disease.

Addressing Treatment Challenges in Advanced HCC

For patients with advanced HCC, treatment options are limited, and recurrence rates remain high. HCC often co-exists with underlying liver dysfunction, posing additional challenges where surgical resection and ablation would have been possible.

While the treatment landscape for HCC continues to improve, therapeutic approaches are currently limited. According to NCCN guidelines, first-line therapies include atezolizumab and bevacizumab, sorafenib, and lenvatinib. But as with any drug, each comes with questions on long-term safety and efficacy, tolerance, and resistance. And so strategies to improve liver function or develop alternative therapies for these patients are crucial.

Promising Avenues for Advancement

HCC remains a complex and challenging disease. However, addressing the unmet needs in screening, diagnosis, and treatment can improve outcomes for patients with HCC. This requires a collaborative effort, and so primary care physicians, oncologists, hepatologists, researchers, and pharmaceutical companies must work together to achieve significant progress.

Here are a few opportunities to improve patient outcomes:

• Regular screening and follow-up of patients who are at risk of HCC
• Evolution of diagnostic tools with increased sensitivity and specificity to achieve early detection of HCC
• Increased expertise in interpreting clinical assessments for HCC and the exploration of machine learning to analyze complex medical data, including imaging and laboratory results, as a potential solution
• Awareness and identification of patients eligible for clinical trials
• Engagement with research on immunotherapies and gene therapies to treat HCC

The future of HCC management lies in a shared commitment to bridge these existing gaps and offer our patients the best possible care.

References:

Parikh ND, Tayob N, Singal AG. Blood-based biomarkers for hepatocellular carcinoma screening: Approaching the end of the ultrasound era? J Hepatol. 2023;78(1):207-216. doi:10.1016/j.jhep.2022.08.036

Singal AG, Llovet JM, Yarchoan M, et al. AASLD Practice Guidance on prevention, diagnosis, and treatment of hepatocellular carcinoma. Hepatology. 2023;78(6):1922-1965. doi:10.1097/HEP.0000000000000466

Benson AB, D’Angelica MI, Abbott DE, et al. Hepatobiliary Cancers, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology. Journal of the National Comprehensive Cancer Network. 2021;19(5):541-565. doi:10.6004/jnccn.2021.0022

Marquardt P, Liu P, Immergluck J, et al. Hepatocellular Carcinoma Screening Process Failures in Patients with Cirrhosis. Hepatol Commun. 2021;5(9):1481-1489. doi:10.1002/hep4.1735

Abboud Y, Ismail M, Khan H, et al. Hepatocellular Carcinoma Incidence and Mortality in the USA by Sex, Age, and Race: A Nationwide Analysis of Two Decades. J Clin Transl Hepatol. 2024;000(000):000-000. doi:10.14218/JCTH.2023.00356