In a systematic review and meta-analysis of 47 studies with 15,158 patients, Amit Singal (University of Texas Southwestern Medical Center) and colleagues found that patients with cirrhosis who underwent surveillance (via liver ultrasound with or without measurement of serum alpha fetoprotein) for hepatocellular carcinoma (HCC) had cancers detected at an earlier stage, were more likely to receive curative instead of palliative treatment, and had longer survival. Across all the studies, the pooled 3-year survival rate was 50.8% among the 4735 patients who underwent HCC surveillance, compared to 27.9% among the 6115 patients without prior surveillance (p<0.001).
The finding of longer survival persisted after the authors limited their review to studies that took into account lead time bias. Lead time bias, as it applies to this study, is the time between when a disease would normally be diagnosed without screening and when the disease is diagnosed with screening. Detecting disease earlier through screening can sometimes appear to increase survival when instead it only prolongs the time the person has the diagnosis. However, in this case, studies that accounted for lead time bias statistically still found that screening increased survival. Among the 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<0.001).
The authors note that while screening for HCC in patients with hepatitis B virus (HBV) infection is supported by a large randomized trial, no such randomized trials exist for patients with cirrhosis. Therefore the authors systematically reviewed published research that evaluated whether screening was associated with improved patient outcomes. While guidelines of the American Association for the Study of Liver Diseases and European Association for the Study of the Liver recommend surveillance with ultrasound every 6 months in high-risk patients (which includes those with chronic HBV infection and/or cirrhosis), the authors note that studies have shown that surveillance in the US is performed in less than 20% of these patients nationally, with lower rates among primary care physicians than gastroenterologists/hepatologists (physicians who specialize in caring for patients with liver disease).
A limitation of the study is that the studies were quite heterogeneous, suggesting benefits of surveillance may not be uniform among all patients, and studies did not include functional status, an important factor in determining appropriate treatment.
The authors conclude, "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."
Funding: This work was conducted with support from UT-STAR, NIH/NCATS Grant Number KL2 TR000453, NIH/NCATS Grant UL1-TR000451, and the ACG Junior Faculty Development Award awarded to AS. The content is solely the responsibility of the authors and does not necessarily represent the official views of UT-STAR, the University of Texas Southwestern Medical Center and its affiliated academic and health care centers, the National Center for Advancing Translational Sciences, or the National Institutes of Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing Interests: The authors have declared that no competing interests exist.
Citation: Singal AG, Pillai A, Tiro J (2014) Early Detection, Curative Treatment, and Survival Rates for Hepatocellular Carcinoma Surveillance in Patients with Cirrhosis: A Meta-analysis. PLoS Med 11(4): e1001624. doi:10.1371/journal.pmed.1001624
Author Affiliations:
Department of Internal Medicine, University of Texas Southwestern Medical Center
Department of Clinical Sciences, University of Texas Southwestern
Harold C. Simmons Cancer Center, University of Texas Southwestern Medical Center
Department of Internal Medicine, Emory University
Contact:
Amit Singal University of Texas UNITED STATES 001-734-657-7894 amit.singal@utsouthwestern.edu
Journal
PLoS Medicine