Screening for hepatocellular carcinoma (HCC) is associated with significant improvement in early tumor detection, receipt of curative therapy, and overall survival in patients with cirrhosis, according to a meta-analysis published in Public Library of Science Medicine (DOI: 10.1371/journal.pmed.1001624).
“There is consistent data that shows a strong association between HCC surveillance and improved outcomes—i.e., detecting cancer at an earlier stage and increased survival—among at-risk patients, including those with cirrhosis,” said the first author, Amit Singal, MD, MS, Assistant Professor of Medicine and Medical Director of the Liver Tumor Program at the University of Texas Southwestern.
HCC, the most common form of primary liver cancer, is the third leading cause of cancer-related death worldwide, and a leading cause of death among patients with cirrhosis, the researchers noted.
For this analysis, Singal and his coauthors—Anjana Pillai, MD, and Jasmin Tiro, PhD—identified 47 studies conducted between 1989 and January 2014 that assessed the impact of HCC surveillance on at least one of the following outcomes:
- The proportion of patients diagnosed with early-stage HCC;
- The proportion of patients with HCC who underwent curative therapy (including liver transplantation, surgical resection, radiofrequency ablation, or percutaneous ethanol injection); or
- Overall survival.
Of a total of 15,158 patients with cirrhosis who had been screened, HCC was detected by surveillance in 6,284 patients (41.4%) and by symptomatic presentation or incidentally outside of a surveillance protocol in 8,874 patients (58.6%).
The key findings were that:
- Of the 38 studies that included data on tumor stage stratified by whether or nor patients underwent screening for HCC, screening for HCC, the rate of patients diagnosed with early-stage disease was significantly higher in patients undergoing surveillance compared with patients whose tumors presented symptomatically or incidentally (the pooled rates being 70.9% vs. 29.9%);
- Of the 34 studies that assessed the association of HCC surveillance and receipt of curative therapy, patients diagnosed with HCC by surveillance were significantly more likely to undergo curative therapy (the pooled rates being 51.6% of patients vs. 23.7%);
- There was a moderately strong positive correlation between early detection rates and curative treatment rates between studies (which the authors note suggest the association between surveillance and receipt of curative treatment is mediated by improved early tumor detection rates); and
- Of the 36 studies that included data on survival stratified by HCC surveillance, screening was significantly associated with increased survival (with a pooled three-year survival rate of 50.8% among patients who underwent HCC surveillance compared with 27.9% of patients without prior surveillance).
“Our study highlighted that current data consistently demonstrate a strong association between HCC surveillance and improved outcomes—i.e., early tumor detection, receipt of curative therapy, and improved survival,” Singal said via email. “Although we should strive to better evaluate the benefits and harms of HCC surveillance in well-conducted prospective studies, it is important for providers to be aware of currently available data supporting HCC surveillance.”
Current guidelines from the National Comprehensive Cancer Network, the American Association for the Study of Liver Diseases, and the European Association for the Study of the Liver recommend regular liver cancer screening for individuals at high risk for the disease—including patients with cirrhosis. But, liver cancer surveillance is not included in recommendations from the U.S. Preventive Services Task Force for patients with cirrhosis.
“Given the lack of consistency between guideline recommendations, HCC surveillance is currently underused in the U.S.,” Singal said. Prior research by his team found that fewer than 20 percent of at-risk patients receive HCC surveillance—and most often the reason for not screening patients is that health care providers are not ordering the testing.
“The preponderance of data showing that HCC surveillance in patients with cirrhosis is associated with improved outcomes should provide sufficient rationale for providers to recommend HCC surveillance in at-risk patients, even in the absence of a randomized trial,” Singal said.