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Surveillance for hepatocellular carcinoma (HCC) in patients with cirrhosis is recommended but 17% received regular testing for HCC(liver cancer)
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Use of surveillance for hepatocellular carcinoma among patients with cirrhosis in the United States: 'Surveillance for hepatocellular carcinoma (HCC) in patients with cirrhosis is recommended but 17% received regular testing for HCC(liver cancer)' - pdf attached
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Hepatology
July 2010
Liver Cancer Triples, NO HCV Testing Funds: Aging with HCV
"in the United States HCC surveillance is not applied as widely as it is in many European and Far Eastern countries"....Liver cancer, primarily ...
www.natap.org/2011/HCV/020511_07.htm
HCC Surveillance is Needed in USA - Hepatitis C and Hepatocellular ...
by M ShermanCorresponding - 2009
However, the intensity of surveillance in the United States has to increase to a level that exists elsewhere in the world before HCC surveillance will ...
www.natap.org/2009/HIV/062109_01.htm
"The incidence of hepatocellular carcinoma (HCC) in the United States has more than doubled during the past two decades.....Several consensus conferences as well as two professional organizations have recommended regular HCC surveillance for patients with cirrhosis who are at risk of developing HCC.10-16 Findings from this study suggest that these recommendations have not been well adopted into clinical practice. In this population-based study, fewer than 20% of HCC patients with previously recorded cirrhosis received the recommended regular surveillance. Approximately 69% of these patients had HCV, HBV, or alcoholic liver disease recorded prior to their HCC diagnosis........The incidence of hepatocellular carcinoma (HCC) in the United States has more than doubled during the past two decades. Although most patients diagnosed with HCC are diagnosed at an advanced stage of disease when survival is poor (5-year survival <5%), when patients receive potentially curative therapy in the form of liver transplantation, surgical resection, or tumor ablation, a considerable improvement in survival is observed (5 years, 40%-70%).6 However, population-based studies in the United States indicate that only 11% of patients with HCC receive these potentially curative treatments.7, 8 Therefore, surveillance for HCC has been advocated to detect HCC at an early stage, when critical treatment can be applied."
Surveillance for hepatocellular carcinoma (HCC) in patients with cirrhosis is recommended but may not be performed. The extent and determinants of HCC surveillance are unknown. We conducted a population-based United States cohort study of patients over 65 years of age to examine use and determinants of prediagnosis surveillance in patients with HCC who were previously diagnosed with cirrhosis. Patients diagnosed with HCC during 1994-2002 were identified from the linked Surveillance, Epidemiology, and End-Results registry-Medicare databases. We identified alpha-fetoprotein (AFP) and ultrasound tests performed for HCC surveillance, and examined factors associated with surveillance. We identified 1,873 HCC patients with a prior diagnosis of cirrhosis. In the 3 years before HCC, 17% received regular surveillance and 38% received inconsistent surveillance. In a subset of 541 patients in whom cirrhosis was recorded for 3 or more years prior to HCC, only 29% received routine surveillance and 33% received inconsistent surveillance. Among all patients who received regular surveillance, approximately 52% received both AFP and ultrasound, 46% received AFP only, and 2% received ultrasound only. Patients receiving regular surveillance were more likely to have lived in urban areas and had higher incomes than those who did not receive surveillance. Before diagnosis, approximately 48% of patients were seen by a gastroenterologist/hepatologist or by a physician with an academic affiliation; they were approximately 4.5-fold and 2.8-fold, respectively, more likely to receive regular surveillance than those seen by a primary care physician only. Geographic variation in surveillance was observed and explained by patient and physician factors. Conclusion: Less than 20% of patients with cirrhosis who developed HCC received regular surveillance. Gastroenterologists/hepatologists or physicians with an academic affiliation are more likely to perform surveillance. HEPATOLOGY 2010
The incidence of hepatocellular carcinoma (HCC) in the United States has more than doubled during the past two decades.1 This increase is at least partially attributable to a rise in hepatitis C virus (HCV)-related HCC.2-5 Although most patients diagnosed with HCC are diagnosed at an advanced stage of disease when survival is poor (5-year survival <5%), when patients receive potentially curative therapy in the form of liver transplantation, surgical resection, or tumor ablation, a considerable improvement in survival is observed (5 years, 40%-70%).6 However, population-based studies in the United States indicate that only 11% of patients with HCC receive these potentially curative treatments.7, 8 Therefore, surveillance for HCC has been advocated to detect HCC at an early stage, when critical treatment can be applied.
A survey study that was conducted in 1998 reported that 84% of hepatologists regularly perform surveillance in patients with cirrhosis.9 Guidelines disseminated from several consensus conferences beginning in 1991, and professional organizations have subsequently recommended HCC surveillance in patients with cirrhosis who are at high risk of developing HCC.10-16 Ultrasound and serum alpha-fetoprotein (AFP) are the most commonly used modalities for HCC surveillance. One randomized, placebo-controlled trial, as well as several observational cohort and case-control studies, have shown that patients who undergo HCC surveillance have an earlier stage of HCC at diagnosis, greater use of potentially curative therapy, and significant reduction in overall as well as cancer-specific mortality compared with patients detected with symptomatic HCC.17-24
The extent of using HCC surveillance in clinical practice is unclear. Two small studies found very low rates of surveillance among patients diagnosed with HCC.25, 26 For example, we previously reported that less than one-third of patients diagnosed with HCC at three Veterans Affairs medical centers during 1998-2003 received any HCC surveillance prior to their HCC diagnosis.25 However, this study and others were limited by a relatively small sample size and inclusion of, predominantly, male veterans.25, 26
To evaluate HCC surveillance in a larger and more representative sample, we have used data obtained from the linked Surveillance, Epidemiology, and End-Results (SEER)-Medicare claims to evaluate the use of prediagnosis HCC surveillance among patients with HCC who had a prior diagnosis of cirrhosis. We also examined several potential determinants of HCC surveillance, including patient, clinical, and physician factors.
DISCUSSION
Several consensus conferences as well as two professional organizations have recommended regular HCC surveillance for patients with cirrhosis who are at risk of developing HCC.10-16 Findings from this study suggest that these recommendations have not been well adopted into clinical practice. In this population-based study, fewer than 20% of HCC patients with previously recorded cirrhosis received the recommended regular surveillance. Approximately 69% of these patients had HCV, HBV, or alcoholic liver disease recorded prior to their HCC diagnosis. Patients who were younger, Asian, diagnosed during more recent years, living in zip codes with higher income or education, or living in urban areas were more likely to have received regular surveillance than other groups. Women were also more likely to receive regular surveillance, which is consistent with other published findings from large database studies.37 Patients seen by a gastroenterologist or hepatologist or by physicians affiliated with medical schools were significantly more likely to have received regular surveillance than patients seen by other types of physicians and in other practice settings. Significant geographic variations were observed in the rates of surveillance, but these were mostly explained by patient-related factors as well as physician-related factors.
Results from our sensitivity analyses confirmed the generally low use of HCC surveillance. First, when all AFP and ultrasound tests were counted as surveillance irrespective of intent, the rates of regular and inconsistent surveillance improved to 35% and 50%, respectively. Although these figures overestimate the true prevalence of HCC surveillance, they remain relatively low. Second, we estimated HCC surveillance in a subset of patients with diagnosed cirrhosis for 3 or more years prior to HCC diagnosis. The rate of routine surveillance remained low (29%) among these patients.
The findings from this study pertained to practices during 1994-2002. Most of the consensus conference statements recommending HCC surveillance were published between 1991 and 2001.10, 12, 13, 16 Approximately 53.7% of the study sample was diagnosed in 2000-2002 (after the consensus conferences) and in these patients regular and inconsistent surveillance was recorded in 20.6% and 37.7%, respectively. A survey in 1998 indicated that most hepatologists claimed that they performed regular surveillance for HCC.9 It is difficult to reconcile these self-reported practices with real-life practices; the survey could have suffered from selection bias, and the otherwise known self-reported exaggeration of compliance with recommended practices. Furthermore, a poor dissemination of the knowledge on how to best use surveillance is further evidenced by the high prevalence of Child C class patients who received regular surveillance. A recent study found that HCC surveillance becomes futile in patients with advanced cirrhosis not listed for transplantation.38 Given that the two cornerstone international guidelines for HCC management were released in 2001 (European Association for the Study of the Liver) and in 2005 (American Association for the Study of Liver Diseases), it is possible that routine HCC surveillance study has progressively improved during more recent years. Indeed, this study found that an increasing proportion of patients received regular surveillance over time (from 9% in 1994-1996 to 21% in 2000-2002) while the proportion of patients who received inconsistent surveillance did not change over time.
Regular surveillance was less frequently observed in rural areas. Much of the geographic variation observed was explained by patient demographic and clinical factors. New Mexico, Utah, and rural Georgia had the lowest regular surveillance rates, with fewer than 5% of HCC patients with cirrhosis residing in these regions receiving regular surveillance. The absence of overt signs and symptoms of liver disease, failure to identify and record them, and/or failure to attach the proper relevance in terms of HCC risk are all possible explanations. In addition, reduced access to care in rural areas likely contributed to the lower rates of surveillance observed in some areas.
Although generally low, regular HCC surveillance was significantly more common in academic or medical school settings than in community-based practices. Patients who were seen by a gastroenterologist or hepatologist were significantly more likely to receive regular surveillance than patients seen by internal medicine or family practice physicians. The reasons for these findings are unknown but could include limited or outdated knowledge, lack of financial incentive, limited infrastructure for providing follow-up reminders, lack or limited access to appropriate testing for positive or equivocal surveillance results (MRI), and limited access to referral for potentially curative therapy (liver transplantation, radiofrequency ablation). This finding suggests that patients with known liver disease should be referred to appropriate specialties.
The study findings should be interpreted within its possible limitations. First, HCC surveillance tests cannot be directly identified from administrative data. We developed and validated an algorithm with good predictive value to identify both AFP and ultrasound tests performed for surveillance purposes. Nevertheless, misclassification is still possible, although, given the very low prevalence of surveillance, the effect of misclassification on the overall findings is likely to be minimal. Second, we were unable to capture physician intention or recommendation to perform a surveillance test and the patients' responses or adherence to these recommendations. Only tests that were actually performed could be identified using our data source, but not tests that were requested but not performed. These issues need to be examined in future studies. Third, the study cohort included only Medicare-enrolled patients who were 65 years of age and older; therefore, the findings may not be generalizable to younger patients. A similar study in younger patients could provide fairly different results, because we found that relatively younger individuals in our cohort were more likely to receive regular surveillance compared with older age groups. However, these limitations are outweighed by the large numbers of patients identified with HCC from the 16 community-based regions across the country, as well as the highly valid and complete cancer and testing data in SEER-Medicare. In addition, results from SEER public access data indicated that 60% of all HCC patients are age 65 and older; thus, our study cohort is representative of a large and relevant segment of patients with HCC.
In conclusion, the use of recommended HCC surveillance is generally low. In addition to patient demographic and clinical characteristics, physician specialty and practice arrangement were highly associated with regular HCC surveillance. Future studies are needed to evaluate the knowledge, attitudes, and barriers for HCC surveillance and to develop appropriate, targeted interventions to increase the dissemination of this practice.
RESULTS
We identified 1,873 patients diagnosed with HCC who had a prior diagnosis of cirrhosis during 1994-2002 who fulfilled our inclusion criteria. The mean age at HCC diagnosis was 74.9 years. Most patients were men (65.7%). The largest proportion of patients was white (81.8%), followed by Hispanic (12.1%), Asian (9.4%), and black (7.9%). Approximately 25% had a previous diagnosis of alcoholic liver disease, 28% had HBV or HCV, and 16% had both alcoholic liver disease and hepatitis. Approximately 37% had a recorded diagnosis of cirrhosis for more than 2 years prior to their HCC diagnosis. The mean number of physician visits within the 3 years prior to HCC was 67.9 (standard deviation 42.4).
Only 17% (n = 321) of patients had received regular HCC surveillance, and an additional 38% (n = 710) had received inconsistent surveillance. Among patients who had received at least one surveillance test, the median number of surveillance tests per patient was 4.0 (1st and 3rd quartiles: 2.7, 5.3). Among 541 patients diagnosed with cirrhosis 3 or more years prior to HCC diagnosis, only 29% received routine surveillance, 33% received inconsistent surveillance, and 38% received no surveillance.
Among all patients who had received regular surveillance, approximately 52% had received a combination of AFP and ultrasound, 46% had received AFP only, and 2% had received ultrasound only. Among those who received inconsistent surveillance, approximately 69% had received AFP only, 15% had received ultrasound only, and 15% had received both tests. Only 59 patients (3.2%) received underwent magnetic resonance imaging (MRI) examination and 1,295 patients (69.1%) underwent CT examination within the 3 years prior to their HCC diagnosis. If we reapply our definition of routine, inconsistent, and no surveillance to include all AFP, ultrasound, CT scans, and MRI tests irrespective of the intention of the test, we observe higher rates of routine surveillance (46.3%). If we exclude CT and MRI examinations performed within 6 months prior to HCC diagnosis, which would have a higher likelihood of being performed for diagnostic purposes, the proportion of patients who received routine surveillance defined by any AFP, ultrasound, CT, or MRI was 43.9%.
Patients who had received regular surveillance were more likely to be younger (P < 0.001), female (P = 0.006), Chinese or other race (P < 0.001), and diagnosed during more recent years (P < 0.001) than those who had not received surveillance (Table 1). Those having a recoded diagnosis of cirrhosis for a longer duration prior to their HCC diagnosis were also more likely to receive surveillance (P < 0.001). Only 9.8% of patients with alcoholic liver disease (in the absence of HCV or HBV) received HCC surveillance compared with 28.5% of patients with HCV or HBV and 32.2% of patients with both alcoholic liver disease and HCV or HBV. Patients with HCC in the absence of HCV, HBV, or alcohol were least likely to receive surveillance (4.9%).
Patients living in zip codes with higher median incomes and larger proportions of residents with more than a high school education were more likely to receive regular HCC surveillance than those living in lower to median income regions or with less than a high school education (P < 0.001 and P = 0.003, respectively). Patients with a greater number of physician visits within the 3 years prior to their HCC diagnosis were more likely to receive HCC regular surveillance compared with patients with fewer physician visits (P < 0.001).
The distribution of physician factors among patients in our study cohort is presented in Table 2. Approximately 48% of patients were seen by a gastroenterologist (n = 722) or hepatologist (n = 116) or both (n = 67) at least once during the 3 years prior to their date of HCC diagnosis. Approximately 58% were seen by an internal medicine or family practice physician at least once during the 3 years prior to their HCC diagnosis, and 21% were seen by another specialist only (cardiology, endocrinology, rheumatology). Almost 32% of patients had an internal medicine or family practice physician as their primary physician prior to their HCC diagnosis, 22% had a gastroenterologist or hepatologist, and 32% had a primary physician in another specialty. Approximately 46% of primary physicians were in a group practice setting, 22% were in solo practice, and 3% were affiliated with a medical school.
Patients seen by a gastroenterologist or hepatologist alone or in combination with an internal medicine or family practice physician were approximately 5 times more likely to receive regular surveillance than those seen by an internal medicine or family practice physician only. Furthermore, a greater proportion of patients whose primary care physician was a gastroenterologist received regular surveillance or at least one surveillance test (P < 0.001) than patients whose primary physician was internal medicine or family practice. Patients having a physician affiliated with a medical school or who graduated from medical school during a more recent period were also more likely to receive regular surveillance (P = 0.0004 and 0.0074, respectively) than other patients.
These associations between receipt of surveillance and physician characteristics persisted in a multivariable logistic regression analysis adjusting for several patient and clinical factors (Table 3). Patients seen by a gastroenterologist or hepatologist only or in combination with an internal medicine or family practice physician were 2.8 and 4.5 times more likely, respectively, to receive regular surveillance than patients seen by an internal medicine or family practice physician only. Patients whose primary physician had an academic affiliation were more than 3 times more likely to receive regular surveillance than patients seen by physicians in solo practice.
We found several significant differences among SEER regions in the receipt of regular surveillance in the unadjusted analysis. The Los Angeles registry had the highest percentage of patients who had undergone regular surveillance (26%). Other registries significantly lower than Los Angeles were Atlanta (OR 0.35; 95% CI 0.15-0.81), Connecticut (OR 0.25; 95% CI 0.12-0.51), Detroit (OR 0.50; 95% CI 0.29-0.84), Iowa (OR 0.37; 95% CI 0.18-0.74), Kentucky (OR 0.33; 95% CI 0.11-0.99), and New Mexico (OR 0.13; 95% CI 0.04-0.44). Most geographic differences were explained by patient and provider factors. In a model adjusting for demographic and clinical factors, only patients residing in the SEER regions of Connecticut and New Mexico remained significantly less likely to receive regular surveillance. After further adjusting for specialty of physicians seen during the past 3 years, we found no significant differences in regular surveillance remaining among SEER regions (data not shown).
SOURCE Medivir
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