Liver Cancer Screening Has Benefits in Patients With Cirrhosis

Megan Brooks

April 11, 2014

Screening for hepatocellular carcinoma (HCC) in patients with cirrhosis has benefits, according to a meta-analysis of published studies.

The meta-analysis was published online April 1 in in PLoS Medicine.

The pooled data show that patients with cirrhosis who undergo surveillance with liver ultrasound with or without serum α-fetoprotein have cancers detected at an earlier stage, are more apt to receive curative instead of palliative treatment, and live longer than their peers who do not have regular surveillance.

These data provide "sufficient evidence" to support regular HCC surveillance among patients with cirrhosis, conclude the authors, led by Amit G. Singal, MD, from University of Texas Southwestern Medical Center, Dallas.

But J. Leonard Lichtenfeld, MD, deputy chief medical officer for the American Cancer Society, isn't so sure.

"The authors did an excellent job of reviewing the literature as it currently exists and they found benefit to screening for HCC," Dr. Lichtenfeld told Medscape Medical News. "They believe that the evidence is sufficient to tip the balance toward screening in patients at high risk, but I'm not certain that everyone would agree that the evidence is sufficient," he said.

Third Leading Cause of Cancer Death

In their paper, Dr. Singal and colleagues point out that globally, HCC is the third leading cause of cancer death and a leading cause of death in patients with cirrhosis. Most HCCs are diagnosed at an advanced stage, precluding potentially curative treatment.

There is level I evidence for the benefit of HCC screening among patients with hepatitis B but only level II evidence in patients with cirrhosis, the researchers note in their article.

However, "the lack of randomized data does not necessarily equate to a lack of efficacy, and the preponderance of data that consistently demonstrate benefits should provide sufficient rationale to recommend HCC surveillance, even in the absence of a randomized controlled trial among patients with cirrhosis," Dr. Singal told Medscape Medical News.

Guidelines from the American Association for the Study of Liver Diseases and European Association for the Study of the Liver both recommend surveillance with ultrasound every 6 months in high-risk patients (which includes those with chronic hepatitis B virus infection and/or cirrhosis). Yet studies have shown that surveillance in the United States is performed in fewer than 1 in 5 of these patients, Dr. Singal and colleagues point out.

To gauge the effect of HCC surveillance in cirrhotic patients, they reviewed relevant literature from 2009 to 2012. They identified 47 studies (most retrospective) that examined the association of HCC surveillance with outcomes in 15,158 patients with cirrhosis who developed HCC.

HCC was detected by surveillance in 6284 (41.4%) patients and presented symptomatically or found incidentally outside of a surveillance protocol in 8874 (58.6%).

The pooled rate of early detection was 70.9% with surveillance vs 29.9% without. The likelihood of early detection was roughly 2-fold higher among patients undergoing surveillance (odds ratio [OR], 2.08; 95% confidence interval [CI], 1.80 - 2.37).

Receipt of curative treatment was also more likely with surveillance (51.3% vs 23.8%; OR, 2.24; 95% CI, 1.99 - 2.52).

Among patients for whom survival data were available, 50.8% of surveillance patients survived for at least 3 years after diagnosis compared with 28.2% of those who had not undergone surveillance (OR, 1.90; 95% CI, 1.67 - 2.17). Among 6 studies that adjusted for lead-time bias, those who underwent HCC surveillance had 3-year survival rates of 39.7% vs 29.1% among those who did not (P < .001).

Dr. Singal and colleagues say caution is needed in interpreting the results, noting that "many of the studies included in the meta-analysis had insufficient follow-up to assess survival adequately, not all the studies adjusted for lead-time bias, and none of the studies assessed potential downstream harms of HCC surveillance such as complications of liver biopsies."

Nonetheless, they believe HCC surveillance is worthwhile in patients with cirrhosis.

However, in an interview with Medscape Medical News, Dr. Lichtenfeld cautioned that "screening is a hot topic these days and sometimes without the appropriate research we find ourselves wanting to believe as opposed to proving the case."

"We may never get an adequate screening test for HCC," he added. This meta-analysis "may be the best evidence that we have and it is subject to expert discussion and interpretation as to what the recommendation should be. And all of this has to be looked at in the context of increasing incidence of cirrhosis. There are a lot of dynamics and no clear answer," Dr. Lichtenfeld concluded.

The study had no commercial funding . Dr Singal and coauthors and Dr. Lichtenfeld have disclosed no relevant financial relationships.

PLoS Med. Published online April 1, 2014. Full text

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