Study and Editorial Address Screening for Hepatocellular Cancer
Hepatocellular carcinoma (HCC) incidence and mortality have increased internationally over the past four decades. The rationale for HCC screening is that imaging tests may identify patients with early-stage disease, and there are several potential options for treatment. However, recommendations for HCC screening remain controversial, in part because of concerns over the quality and paucity of existing evidence, as well as concerns about over-diagnosis and potential patient harms from screening itself and from the treatment of early-stage HCC. This study sought to review the benefits and harms of HCC screening in patients with chronic liver disease. Investigators conducted a review of the literature from database inception to April 2014. Of more than 13,000 citations, 22 studies met the study inclusion criteria.
While screening for hepatocellular cancer can identify more patients with earlier stage disease who are candidates for potentially curative treatments, there is very limited evidence upon which to draw firm conclusions about the balance of health outcome benefits and harms of using routine screening to identify HCC. One large trial in China found decreased mortality from HCC with periodic ultrasound screening but was limited by methodological flaws. Another smaller trial of alpha-feto-protein screening in hepatitis B patients and two trials of more frequent vs. less frequent ultrasound screening found no survival benefit. In 18 observational studies, screened patients had earlier stage HCC and longer survival after diagnosis than those clinically diagnosed with HCC, but lead- and length-time bias prevent concluding that mortality was reduced by screening. Therefore, the body of evidence that serves as the basis for current recommendations for screening has substantial shortcomings.
- Only English-language studies were included in this review.
- The evidence base was limited by methodological issues and a paucity of trials.
EDITORIAL: SUMMARY OF KEY POINTS
- Screening has a much greater potential to produce benefits exceeding harms in the highest-risk patients, such as those with hepatitis C and cirrhosis than in the general population. Although current screening programs should not be expanded, it is reasonable to allow clinicians caring for these patients to continue to offer screening, but offers should be targeted to those who are good candidates for treatment and should include a shared decision-making approach that explicitly acknowledges the limitations of the evidence.
- Screening should be paired with efforts to collect better data, including baseline characteristics and long-term outcomes in both screened and unscreened patients, which may help reduce uncertainty about outcomes. In VA and other integrated healthcare systems with electronic records and cancer registries, most of these data can be collected as part of routine clinical care. Given the high mortality from HCC and the high costs of delivering a truly effective program of early detection and treatment, better evidence is imperative.
The study was funded by VA/HSR&D's Quality Enhancement Research Initiative (QUERI). Dr. Kansagara is part of HSR&D's Center to Improve Veteran Involvement in Care, Portland, OR, and also is part of HSR&D's Evidence-Based Synthesis Program.
Editorial: Dr. Atkins is Director of HSR&D, Washington, D.C.; Dr. Ross is Director of the HIV, HCV, and Public Health Pathogens Programs, VA Office of Public Health, Washington, D.C.; and Dr. Kelley is National Program Director for Oncology, Durham VA Medical Center.
Kansagara D, Papak J, Pasha A, et al. Screening for Hepatocellular Cancer in Chronic Liver Disease: A Systematic Review. Annals of Internal Medicine. June 17, 2014;e-pub ahead of print.