Hepatocellular Carcinoma Surveillance in Focus

Lauren Mays Weddle, PhD
Published: Saturday, Sep 19, 2015
Controversy over optimal surveillance methods for hepatocellular carcinoma (HCC) continues to drive ongoing investigation into improved biomarkers and imaging techniques. Recent screening studies have focused on the utilization of alpha-fetoprotein (AFP) with ultrasound and abbreviated MRI approaches.

An article published in the American Journal of Gastroenterology demonstrated that AFP may be a helpful complement to traditional ultrasound-based surveillance programs, one that is particularly useful among patients with viral-induced cirrhosis.1 Additionally, MRI and CT are occasionally employed as a means of increasing HCC detection sensitivity among high-risk patients in place of conventional ultrasound. According to one recent study, per-patient sensitivities for HCC detection were 64%, 76%, and 85%, for ultrasound, CT, and MRI, respectively.2

Although alternative imaging techniques offer the potential for improved sensitivity, limiting factors often prevent their widespread use as an HCC surveillance tool. For instance, “despite higher diagnostic accuracy than ultrasound and CT,” explained Robert M. Marks, MD, from the Naval Medical Center San Diego, “the greater expense, long examination times, and relatively limited availability remain a challenge to using MRI in HCC surveillance.”3 Due to the factors limiting CT and MRI approaches, “their roles as surveillance tools for detecting early-stage HCC in patients with cirrhosis remain uncertain,” noted Te-Sheng Chang, MD, PhD, and colleagues in their recent report on the addition of AFP.1 The use of MRI, for instance, may be better suited to confirming positive surveillance results, rather than screening for HCC initially.3

In answer to these limitations, a recent study by Marks and colleagues in the American Journal of Roentgenology attempted to model an abbreviated MRI examination protocol and assess its potential as an HCC surveillance tool.3 With a gadoxetic acid-enhanced hepatobiliary phase and T2-weighted single-shot fast spinning echo (SSFSE), the abbreviated protocol was able to maintain the high per-patient sensitivity and negative predictive value of the MRI technique, while minimizing logistic limitations, such as cost and procedure time.3

“We found that per-patient sensitivity for the detection of HCC with an abbreviated MRI examination was similar to the reported sensitivity for the complete study with gadoxetic acid,” wrote the authors.3 According to their findings, the abbreviated protocol reached 82.6% sensitivity, which is not only comparable to the complete MRI, but also considerably greater than that reported in the literature for ultrasound-based surveillance.4,5

Resources such as the abbreviated MRI procedure may be useful for improving surveillance sensitivity and identifying patients requiring follow-up with more costly and time-intensive imaging techniques. With the potential to reduce the current 20 minute to 40 minute procedure time to a 15-minute time slot and 5-minute scan, the authors estimated that switching from a complete MRI to an abbreviated MRI surveillance program may afford a total cost savings of nearly 31%.3 Overall, the study by Marks and colleagues concluded that the abbreviated MRI technique may be beneficial for centers currently utilizing full-length MRI for HCC surveillance.3 The authors went on to stress that additional studies are still necessary to determine the relative cost-to-benefit ratio of utilizing this technique compared with the conventional ultrasound approach.3

Role of Biomarkers for Improving Ultrasound Sensitivity

Until alternative surveillance modalities, such as the abbreviated MRI, are thoroughly validated and widely available, methods for improving ultrasound sensitivity are of critical importance. In the absence of alternative modalities, several groups have investigated the utility of serum biomarkers, such as AFP, as potential surveillance tools. By itself, however, AFP has proved suboptimal in detecting HCC.6–8

“There have been false-positive results, as elevated AFP also occurs in chronic liver disease and other malignancies,” explained Chang and colleagues in their recent report.1 False-negative results may also occur when using this biomarker, as not all HCCs secrete AFP. “This is particularly veritable for early- stage HCCs, which are the targets of surveillance,” added the authors.1

Due to these potential limitations, the American Association for the Study of Liver Diseases (AASLD) and the European Association for the Study of the Liver (EASL) recently discouraged the use of AFP as a surveillance modality for HCC.9–11 Despite this, interest remains as to whether the biomarker may still provide some benefit when used as a complement to conventional ultrasound.1,12

Since ultrasound is a subjective, highly operator- dependent technique, Chang explained that “the detection of increased AFP levels during surveillance may alert the surveyor and thus trigger a more intense survey.”1

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