Although HCC surveillance is recommended by the AASLD and is considered to be standard-of-care by many physicians, our meta-analysis highlights its underutilization in clinical practice. Low utilization rates were first reported by Leykum and colleagues11
and have been replicated in several studies, including three analyses from multi-center databases.7,8,12
Our systematic review is the first to critically summarize these studies and document the socio-demographic disparities in HCC surveillance programs. Most studies found surveillance rates below 30%, although rates of 60-80% were reported in single-center studies from tertiary care and/or community practices. There were also significant socio-demographic disparities with the lowest surveillance rates in non-Caucasians and patients of low SES.
Surveillance rates in HCC are substantially lower than those currently seen for other cancers. In fact, surveillance rates for colon, breast, and cervical cancer are currently greater than 60% for most of the United States.25
This difference in surveillance rates is likely due to a combination of issues, including under-recognition of at-risk individuals with cirrhosis and poor education of primary care physicians regarding the importance of HCC surveillance.
HCC surveillance is a complex process, with multiple steps that are prone to failure.26
Providers must accurately identify high-risk patients, they must refer these patients for surveillance, the healthcare system must schedule the tests, and patients must comply with surveillance recommendations.27
This challenge is even more relevant in primary care settings, where providers face increasing time constraints and might be less knowledgeable about HCC guidelines. Current studies fail to provide an in-depth analysis to clarify which factors mediate or moderate underutilization of HCC surveillance. Future research should investigate correlates of these breakdowns to identify appropriate intervention targets.
Under-recognition of patients with cirrhosis may be an important factor in the low surveillance rates for HCC. Many patients with well-compensated cirrhosis are asymptomatic, but they remain at high risk for developing HCC and warrant surveillance. This was suggested in the SEER-Medicare study, as HCC surveillance rates were substantially higher in patients with recognized cirrhosis than the remainder of the cohort (29% vs. 17%).8
Similarly, Stravitz and colleagues reported that 21.9% of patients were not recognized as having cirrhosis prior to their HCC diagnosis.28
It is possible that some patients with unrecognized cirrhosis could be identified using non-invasive fibrosis markers, which would permit earlier application of appropriate surveillance. Unfortunately, this intervention would likely be insufficient in isolation given that surveillance rates among patients with known cirrhosis are still disappointingly low, suggesting the need for concurrent issues to be addressed.
Patients who received subspecialty care from gastroenterologists/hepatologists had significantly higher surveillance rates than patients followed by primary care physicians (52% vs. 17%, p
0.001). Four studies evaluating patients followed in subspecialty clinics reported the highest utilization of surveillance, with all having rates of 60–80%.10,13–15
Three studies were conducted in tertiary-care academic centers, but this finding was also replicated in a community-based gastroenterology practice. Subspecialty care was also a strong predictor of surveillance utilization in the North Carolina Medicaid health claims and SEER-Medicare databases.8,12
Although socioeconomic status and access to care could be potential confounding factors in this relationship, the association between subspecialty care and surveillance utilization persisted on multivariate analysis after adjusting for patient-level and system-level factors.8
These results suggest that differences in surveillance rates are likely related to variation in provider knowledge and attitudes, rather than patient-level factors such as socioeconomic status or system-level factors related to the academic center.
Currently, primary care physicians follow most patients with cirrhosis nationally, with only 20–40% of cirrhotic patients being followed by gastroenterologists or hepatologists.8
Unfortunately, referring every patient with cirrhosis to a subspecialist is not a viable option, particularly given limited availability of subspecialty care in some areas. Accordingly, educating primary care physicians how to recognize patients with cirrhosis and about the importance of HCC surveillance is one crucial step to improve surveillance rates. Per current AASLD guidelines,3
primary care education should reinforce that AFP is an effective screening tool only if used in conjunction with imaging studies. Further studies are necessary to characterize the effect of provider factors on surveillance utilization and develop intervention strategies to increase HCC surveillance rates through primary care clinics.
Racial and socioeconomic disparities have been well described in the survival of patients with HCC.16
Although prior studies have suggested difference in tumor biology and/or delivery of treatment, our meta-analysis is the first to highlight the importance of socio-demographic disparities. Patients who are elderly, non-Caucasian, and of low SES suffer from significantly lower HCC surveillance rates than their counterparts. While current studies suggest an association between socio-demographic factors and HCC surveillance practices, none have explored why surveillance is not being performed in these subgroups. The roles of patient attitudes, co-morbid conditions, and barriers to accessing care have not been clearly evaluated. For example, elderly patients and patients of low SES may have lower surveillance rates due to difficulty accessing medical care or a higher rate of co-morbid conditions that would limit the benefit of surveillance. Similarly, race and SES are often highly correlated so independent causal effects can be difficult to identify. It is important to note that current studies were all performed in highly uniform populations, with the majority of patients being male, Caucasian, and insured so confirmatory studies in racially and socioeconomically diverse patient populations are necessary.
The primary limitation of our meta-analysis was our inability to identify specific reasons for underutilization of HCC surveillance. Current studies did not distinguish cases in which physicians failed to order surveillance from cases in which surveillance was not appropriate (e.g., patients with significant co-morbidities or those with Child C cirrhosis who were not transplant candidates) or cases in which patients were non-adherent after surveillance was recommended. Studies evaluating the reasons behind surveillance under-utilization are necessary to identify intervention targets that can increase surveillance rates. Furthermore, all studies to date have evaluated homogeneous populations, and studies in racially and socioeconomically diverse populations are necessary. Finally, many studies use operational definitions for surveillance that are not consistent with AASLD guidelines. Only six studies assessed utilization every 12 months, and none reported surveillance with six-month intervals. Additionally, over one-third of patients in several studies had surveillance with AFP alone, which is contrary to current guidelines. The recent change in AASLD guidelines to six-month surveillance intervals suggests it is important for future studies to use stringent definitions of surveillance when assessing utilization. This variability in definitions used for surveillance makes it difficult to compare surveillance rates across studies. Clear consistent definitions and measures are necessary to better interpret and quantify HCC surveillance rates.24
In summary, HCC surveillance is underutilized nationally with most studies reporting rates below 30% and a pooled surveillance rate of 18.4%. Subspecialty care appears to be the strongest predictor of higher surveillance rates, with several studies demonstrating utilization rates of 60-80% in patients followed by gastroenterologists/hepatologists. There are also significant socio-demographic disparities with the lowest surveillance rates in non-Caucasians and patients of low SES. Further studies are needed to explore reasons for the underutilization of surveillance, particularly in these disadvantaged subgroups. These studies will be the first crucial step in identifying appropriate intervention targets to increase HCC surveillance rates and reduce socio-demographic disparities.