The ultimate goal of cancer screening is to reduce one’s risk of cancer-related death. In the case of screening for liver cancer, the story is still evolving, but new studies continue to suggest that it may not achieve this goal.
Screening tests for different types of cancer have presented a mixed picture on the overall utility of screening. Some, such as Papanicolaou (Pap) smears to screen for cervical cancer, have clear value in detecting cervical cancers at a earlier, more treatable stages and improving long-term survival. Others, such as prostate-specific antigen (PSA) levels to screen for prostate cancer, are more in doubt, as studies indicate that the benefits of PSA testing are small at best, and the harms of unnecessary treatment can be significant.
A systematic review released today in the Annals of Internal Medicine about screening tests for liver cancer in high-risk individuals (those with liver cirrhosis or chronic hepatitis B infection) found that overall, the evidence is of low quality and offers no proof that screening these individuals offers any advantage in extending life or in decreasing mortality from the disease.
This review, funded by the US Department of Veterans Affairs, included 18 observational studies and 4 clinical trials that studied the issue. After a careful assessment of the methods and results of all the studies, the authors concluded that the 2 largest randomized clinical trials, both conducted in China, had “substantial methodological flaws” that threatened the validity of their results. One study showed that routine screening with liver ultrasound and alpha-fetoprotein testing was associated with reduced liver cancer mortality, but the other showed no effect. Furthermore, most of the patients in these 2 studies had chronic hepatitis B infection as the cause of the their chronic liver disease, whereas the majority of people in the United States with chronic liver disease have chronic hepatitis C infection or alcoholic liver disease.
The 18 observational studies included a wider range of geographic settings and more patients with hepatitis C infection; however, the results on mortality reduction resulting from screening were still mixed. Given the inherent bias present in observational studies, the authors state that these studies “do not contribute substantially to the strength of evidence.” Overall, the results did suggest that liver cancers diagnosed as a result of screening tended to be at an earlier stage than those diagnosed clinically in the absence of screening, but the “lead time bias” in these findings makes any true effects on mortality questionable. In other words, people may perceive they are living longer because of a longer period between diagnosis and death, but that longer period may simply be the result of earlier diagnosis and not of extending lifespan.
None of the studies examined the harms of screening, which can include psychological stress, needle-track “seeding” of cancer cells as a result of biopsy, and overdiagnosis, a concept that refers to finding very slow-growing tumors that never would have otherwise caused problems in a patient’s lifetime.
Current guidelines by the American Association of Liver Diseases recommend screening for liver cancer with ultrasound every 6 months for all individuals with cirrhosis, and for some individuals with chronic hepatitis B infection in the absence of cirrhosis. The US Preventive Services Task Force has not released official guidelines on the topic. The authors suggest that there are still major evidence gaps that need to be addressed before more solid guidelines can be created, but also recognize that conducting large-scale randomized trials in the United States or Europe that focus on this specific clinical question in this patient population may not be feasible.