Precision Screening May Improve Surveillance in HCC

Amit G. Singal, MD, MS

During a presentation at the 2017 International Liver Cancer Association Annual Conference, Amit G. Singal, MD, MS, stressed that precision screening for hepatocellular carcinoma (HCC) could improve on current screening techniques through its risk-stratifying approach.

The current standard of care for HCC surveillance is ultrasound with or without serum biomarker including alpha fetoprotein. Not only is this approach highly operator-dependent, but patient characteristics such as obesity, liver nodularity and echogenicity, and presence of ascites can limit accuracy.

“The highest rates of HCC are in east Asia and Africa, primarily driven by high rates of hepatitis B in those areas. While the incidence of HCC is lower in the United States and Europe, it is gaining a lot of attention because HCC has the largest increasing incidence among all solid tumors over the past 10 years as assessed by SEER,” said Singal, medical director of the Liver Tumor Program at UT Southwestern Medical Center. “Some projections have HCC becoming a top 5 cause of cancer-related death over the next decade in the United States. One of the key ways to curb this increased mortality is to increase rates of early tumor detection and curative treatment.”

Surveillance is recommended by professional society guidelines such as the American Association for the Study of Liver Diseases Practice Guideline, the National Comprehensive Cancer Network, and the Asian Pacific Association for the Study of the Liver.

HCC surveillance reduces mortality in patients with chronic hepatitis B and is associated with improved survival in patients with cirrhosis. However, only a minority of at-risk patients are diagnosed at an early stage where they can be treated with curative therapies.

“This is related to several different reasons, but one of the most important factors is that our current surveillance tests are not optimal,” Singal said.

Considering the climbing rate of HCC-related death around the globe, Singal proposes precision screening as a first step to identify risk more accurately than traditional methods.

While the risk models in chronic hepatitis B have achieved fairly good accuracy, Singal said that the clinical variables in patients with cirrhosis do a poor job in terms of stratifying patients into low-, intermediate-, and high-risk classifications.

Tissue-based signatures can be used to stratify patients into high-risk, intermediate-risk, and low-risk for HCC in patients with cirrhosis. Though gene signature can accurately risk stratify patients in terms of HCC risk, due to the heterogeneity of HCC, risk varies substantially between individual patients, so a more personalize approach is needed. This approach has been traditionally difficult to implement given the gene signature is limited to tissue-based; however, recent data suggest a serum-based signature can accurately mirror the tissue signature.

Singal proposed a novel approach of precision screening that uses a serum-based signature, by which clinicians would be able to determine at what intensity individual high-risk, intermediate-risk, and low-risk patients can receive surveillance.

“Instead of applying a one-size-fits-all strategy to patients, it is about figuring out the best tests for each individual patient, and tailoring how we do surveillance to their individual risk,” said Singal.

Precision screening maximizes benefits and cost-effectiveness of screening, while minimizing the harms that come with surveillance, said Singal, sparing patients who are at a lower risk from intense surveillance.

Additionally, the rise in HCC-related mortality in the United States is not aided by the growing rate of obesity, which hinders proper traditional screening such as ultrasound—making precision screening a particularly important option for this patient population.

Singal said that the benefits of this approach include earlier detection of cancer, minizing harm to lower-risk patients, and avoiding unnecessary diagnostic testing.

“The goal of this talk is to present a vision of where we should be in terms of screening, hopefully 5 years from now,” Singal said. “The key thing to take away is that our goals as clinicians should really be to optimize the value of everything we do, including screening.”

Singal AG. Precision screening: hope or hype. Presented at: 2017 International Liver Cancer Association Annual Conference; September 14-17, 2017; Seoul, South Korea.

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