Combining Ultrasound With Blood Test Improves Early Liver Cancer Detection, Analysis Shows

NEW YORK (360Dx) – Researchers at UT Southwestern's Simmons Cancer Center have found that combining ultrasound imaging with a blood test for levels of alpha fetoprotein (AFP) improves the detection of early-stage liver cancer by as much as 40 percent.

The researchers reported in the journal Gastroenterology last week that by conducting a meta-analysis of 32 previous studies, they found that combining a blood test for alpha fetoprotein with ultrasound increased the detection of early-stage liver cancer, or hepatocellular carcinoma (HCC), from 45 percent with ultrasound alone to 63 percent using the combined method.

Amit Singal, associate professor of internal medicine and clinical sciences with UT Southwestern, said in a statement that most liver cancers in the US are discovered at later stages when curative treatment is not possible. Clinicians have traditionally done cancer screening in patients with chronic liver disease using abdominal ultrasound, which is readily available and noninvasive but misses many cancers when they are small, he said, adding, "If the cancer is found early, then we can perform curative therapies, allowing patients to live many years."

Levels of AFP, a plasma protein produced by liver cells, are normally low in adults.

In the study, the researchers noted that there has been "considerable debate" over the benefits of adding AFP to ultrasound-based surveillance for HCC. A randomized clinical trial would be the best method to put the debate to rest. However, they said, a previous attempt at such a trial comparing ultrasound alone with ultrasound and AFP was not possible due to the high rate of AFP contamination in the ultrasound-alone part of the study. 

As a result the UT Southewestern study "may represent the highest level of evidence possible comparing the two surveillance tests," they wrote.

In their study, the UT Southwestern researchers searched the Medline and Scopus databases from January 1990 through August 2016 to identify the sensitivity and specificity of surveillance strategies for overall and early detection of HCC. Thirty-two studies of 13,367 patients characterized sensitivity of imaging with or without AFP measurement for detection of HCC in patients with cirrhosis, the researchers said.

They noted that ultrasound detected HCC at any stage with an 84 percent sensitivity, but at an early-stage with "only 47 percent sensitivity." Using ultrasound with AFP did result in a "small but statistically significant trade-off in specificity," they said.

They further acknowledged that the studies that comprised their meta-analysis had limitations, including most studies reported only the detection of HCC at any stage, instead of early-stage HCC "which overestimates surveillance test performance." The studies also did not compare differences in downstream outcomes, such as overall survival, and they did not include additional follow-up or use a "gold standard" reference test in patients with normal surveillance tests to confirm they did not have HCC. 

Additionally, many studies did not include factors that may affect ultrasound quality, such as operator experience or the proportion of obese patients, "so we could not identify subgroups in whom ultrasound alone may be sufficient."

However, they pointed out that "[a]lthough these limitations may affect point estimates, they should affect ultrasound and AFP equally, so our analysis comparing ultrasound with and without AFP should be unaffected."