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Healthcare Costs Related to Treatment of Hepatocellular Carcinoma Among Veterans With Cirrhosis in the United States - $7.2 Bill in 2016
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Clinical Gastroenterology and Hepatology Jan 2018 - David E. Kaplan, Michael K. Chapko, Rajni Mehta, Feng Dai, Melissa Skanderson, Ayse Aytaman,k Michelle Baytarian, Kathryn D’Addeo, Rena Fox,# Kristel Hunt, Christine Pocha, Adriana Valderrama, and Tamar H. Taddei for the VOCAL Study Group
Corporal Michael J. Crescenz VA Medical Center, Philadelphia, Pennsylvania; Northwest Center for Outcomes Research in Older Adults, Health Services Research and Development Service, VA Puget Sound, Seattle, Washington; VA Connecticut-Healthcare System, West Haven, Connecticut; kVA New York Harbor Health Care System, Brooklyn, New York; Boston VA Healthcare System, Boston, Massachusetts; #San Francisco VA Medical Center, San Francisco, California; James J. Peters VA Medical Center, Bronx, New York; University of South Dakota, Sioux Falls, South Dakota; and Bayer HealthCare Pharmaceuticals, Whippany, New Jersey
Discussion
We estimate that cost of care for HCC averages $154,688 during 3 years of follow-up, compared with $69,010 in age- and CTP-matched cirrhotic controls who do not develop cancer, yielding an incremental cost of $85,679. The estimated PPPY and per-patient-per-month cancer-specific costs were $147,912 and $12,326, respectively. Although it is difficult to compare VA with non-VA cost expenditures, most recent estimates are that VA costs are generally about 17% lower than costs incurred by Medicare.34, 35 Extrapolating to the U.S. population, the cancer-specific costs for treatment of 40,000 incident cases in 2016 would have approximated $4.4 billion, and the total cost of care would have approximated $7.2 billion.....[The cost-effectiveness of therapies that can prevent HCC development by reducing progression to cirrhosis or by detecting cancer at earlier, curative stages should be re-evaluated in the context of these new comprehensive measurements of HCC-related costs......The mean 3-year total cost of care in HCC patients was $154,688 (standard error of the mean, $150,953-$158,422) compared with $69,010 (standard error of the mean, $67,344-$70,675) in age- and CTP-matchedcirrhotic controls, yielding an incremental cost of $85,679.......Cancer cases were matched 1:4 with non-cancer cirrhosis controls on the basis of severity of liver disease, age, and comorbidities to estimate background cirrhosis-related costs. Univariable and multivariable generalized linear models were developed and used to predict cancer-related overall cost.]
Our measurements of the costs related to HCC care significantly exceed most previous estimates. Some of the differences may reflect temporal evolution of treatments used for HCC, such as increased utilization of transarterial chemoembolization and sorafenib after 2008. The dominance of costs related to inpatient length of stay has never been previously observed, suggesting that comprehensive capture of these costs may also partially explain the higher costs. For instance, the most recent estimates from the SEER-Medicare registry in 2009 approximated $35,011 annual costs,12 but the costs of cirrhosis and, in particular, inpatient care were extremely low, suggesting possible underestimation. Estimates of HCC annual costs from a managed care database yielded fairly similar results to the SEER-Medicare data, with $43,761 PPPY incremental cost over non-hepatitis C-infected individuals.9 By contrast, our estimates are fairly similar to median costs derived from a smaller, single-center estimation of patients with HCC managed at a transplant center, in which median patient cost was $176,456.7 In that series, non-transplant case median total cost was estimated at $91,505, and the incremental cost associated with transplantation was only ∼$100,000, both significantly lower than our estimates of $154,688 and $422,007, respectively, in a similar population. Possible reasons for the differential costs could include the nature of palliative/bridging interventions used, the comprehensiveness of cost accounting, or health system efficiencies.
Inpatient costs were notably dominant over outpatient costs, accounting for 65%-80% of HCC-related costs with an average of 26 additional hospital days for HCC patients over CTP-matched controls. The balance of treatment-related versus decompensation-related hospitalization days merits further investigation. Patients with more advanced CTP B-C cirrhosis incur higher inpatient costs, most likely related to management of hepatic decompensation events, and lower outpatient costs related to cancer treatment. Identifying patients at high risk for intervention-related decompensation that may be better managed with palliative care approaches could reduce morbidity, improve quality of life, and control costs.
Largely because of limitations of the SEER registry, few data explore the impact of clinically used liver cancer staging on outcomes and cost. Patients with early stage HCC (BCLC 0-A) accrued significantly higher costs than patients with intermediate to advanced stage disease, with lowest overall costs in BCLC C patients. Likely because BCLC includes CTP status, when both CTP class and BCLC stage were included in GLM cost models, CTP class yielded insignificant coefficients, thus allowing development of a simplified model that was based on transplantation and BCLC that accurately predicts 3-year costs. This model may be of use for health systems and third-party payers for predicting the impact of increased HCC incidence anticipated during the next decade on future liver disease-related costs.
Another novel finding was that care processes critically impact cost. Liver cancer surveillance, associated with more frequent detection of BCLC 0-A cases, was associated with increased costs. Increased costs with surveillance could reflect longer patient survival or higher use of transplantation but also correlated significantly with management at academically affiliated centers and those with MDTB, factors that independently associated with cost. MDTB discussion correlated with higher costs but also with improvements in survival rates after adjusting for BCLC stage, resulting in lower PPPY costs ($174,484 versus $250,491). MDTB was most cost-efficient in non-transplanted BCLC C patients because of the strong impact of this process on survival (126-day increase). Unlike in the community, patient receipt of care at an academically affiliated VA is primarily determined by geography rather than socioeconomic status or motivation to seek tertiary care. We found that management at academically affiliated VAs had effects on cost independent of MDTB, with more efficient, lower cost care provided for early stage patients. By contrast, BCLC C patients managed at academic centers had significantly greater costs expended ($16,144), with a modest 41 days of survival gained. Only $6026 of this difference was directly attributable to sorafenib pharmacy costs. Therefore, we postulate that other interventions with high cost (eg, 90Y-embolization, radiotherapy) but modest impact on survival potentially account for lower cost-efficiency in BCLC C.
Strengths of this study include cohort size, cohort characterization, comprehensiveness of cost acquisition, and completeness of capture of confounding variables. However, as with any observational cohort study, there is potential for unmeasured confounding. Veterans may have differential access to certain services as well as divergent survival outcomes than the general U.S. population. Although tumor staging was abstracted from chart review, ICD9-CM diagnosis codes and CPT codes were used to determine comorbidity, underlying liver disease, and treatments, possibly introducing misclassification bias. Cost accounting in the VA is not claims based and thus may be difficult to generalize because the costs of specific interventions (eg, a single episode of transarterial chemoembolization) are difficult to estimate.
Conclusion
HCC care consumes tremendous healthcare resources, likely higher than previously estimated. As HCC incidence increases and more expensive interventions are developed, the burden HCC places on U.S. healthcare will increase. The cost-effectiveness of therapies that can prevent HCC development by reducing progression to cirrhosis or by detecting cancer at earlier, curative stages should be re-evaluated in the context of these new comprehensive measurements of HCC-related costs.
Background & Aims
It is important to quantify medical costs associated with hepatocellular carcinoma (HCC), the incidence of which is rapidly increasing in the United States, for development of rational healthcare policies related to liver cancer surveillance and treatment of chronic liver disease. We aimed to comprehensively quantify healthcare costs for HCC among patients with cirrhosis in an integrated health system and develop a model for predicting costs that is based on clinically relevant variables.
Methods
Three years subsequent to liver cancer diagnosis, costs accrued by patients included in the Veteran’s Outcome and Cost Associated with Liver disease cohort were compiled by using the Department of Veterans Affairs Corporate Data Warehouse. The cohort includes all patients with HCC diagnosed in 2008-2010 within the VA with 100% chart confirmation as well as chart abstraction of tumor and clinical characteristics. Cancer cases were matched 1:4 with non-cancer cirrhosis controls on the basis of severity of liver disease, age, and comorbidities to estimate background cirrhosis-related costs. Univariable and multivariable generalized linear models were developed and used to predict cancer-related overall cost.
Results
Our analysis included 3188 cases of HCC and 12,722 controls. The mean 3-year total cost of care in HCC patients was $154,688 (standard error, $150,953-$158,422) compared with $69,010 (standard error, $67,344-$70,675) in matched cirrhotic controls, yielding an incremental cost of $85,679; 64.9% of this value reflected increased inpatient costs. In univariable analyses, receipt of transplantation, Barcelona Clinic Liver Cancer (BCLC) stage, liver disease etiology, hospital academic affiliation, use of multidisciplinary tumor board, and identification through surveillance were associated with cancer-related costs. Multivariable generalized linear models incorporating transplantation status, BCLC stage, and multidisciplinary tumor board presentation accurately predicted liver cancer-related costs (Hosmer-Lemeshow goodness of fit; P value ≅ 1.0).
Conclusions
In a model developed to comprehensively quantify healthcare costs for HCC among patients with cirrhosis in an integrated health system, we associated receipt of liver transplantation, BCLC stage, and multidisciplinary tumor board with higher costs. Models that predict total costs on the basis of receipt of liver transplantation were constructed and can be used to model cost-effectiveness of therapies focused on HCC prevention.
Hepatocellular carcinoma (HCC) incidence and mortality in the United States continue to increase; it is the fifth and ninth leading cause of cancer death in men and women, respectively.1 Therapeutic options used for HCC, including liver resection, liver transplantation, ablative therapies, transarterial embolotherapy/radiotherapy, systemic therapy, and palliative care, are associated with widely ranging and often profound costs. Accurate estimates of HCC-related costs are critically needed to understand the societal burden of chronic liver disease as well as to evaluate the cost-effectiveness of interventions designed to reduce HCC incidence and/or promote early diagnosis. For instance, cost-effectiveness analyses related to high-cost antiviral regimens for chronic hepatitis C are dependent on accurate estimates of the costs of hepatic complications prevented through cure.2, 3 Similarly, the cost-effectiveness of HCC surveillance programs is partially predicated on the differential costs of cancers identified earlier by surveillance.4, 5
Estimates of 3- to 10-year total costs for HCC care have ranged widely from $12,6836 to $176,4567 largely on the basis of the interventions available to the study population.6, 7, 8, 9, 10, 11, 12 Several important limitations of these previous analyses include (1) utilization of the Surveillance Epidemiology and End Results (SEER)-Medicare registry8, 12 that contains limited clinical data on mainly elderly patients who are less likely to receive recommended treatments13 and who are often not considered candidates for high-cost interventions such as liver transplantation13, 14; (2) utilization of cost data predating the introduction of systemic and radiotherapy therapy for HCC6, 8, 9, 11; (3) incomplete capture of transplant-related costs9; (4) limitation of analysis to patients with viral hepatitis7, 9, 12; and/or (5) biases related to selection from a liver transplantation waitlist population.7 A unique feature of HCC is its close association with cirrhosis, a condition with significant and partially independent costs9, 15 that often dictates the nature of safe and effective treatment modalitiHealthcare Costs Related to Treatment of Hepatocellular Carcinoma Among Veterans With Cirrhosis in the United States - $7.2 Bill in 2016es.16 Liver cancer progression generally hastens death through liver failure rather than through complications of metastatic disease, possibly shifting costs toward inpatient management of complications such as ascites, encephalopathy, and variceal bleeding as opposed to progressively intense outpatient systemic therapies. Few studies have analyzed the impact of cirrhosis severity or cancer stage at presentation on subsequent HCC-related costs.7
The Veterans Affairs (VA) medical system is the largest integrated provider of liver-related healthcare in the United States, caring for more than 60,000 patients with cirrhosis and more than 2000 incident cases of HCC annually since 2010.17 Although predominantly male, veterans with HCC in the VA represent both non-elderly and elderly patients with a wide range of liver disease etiologies cared for in urban, suburban, and rural care settings.18 Comprehensive clinical, pharmacy, laboratory, radiology, and procedural data, and costs associated therewith, performed within the VA or paid by VA funds are administratively accessible. In this study, our objective was to quantify absolute per-patient costs of HCC care as well as the relative cost of HCC above costs associated with underlying cirrhosis stratified by liver disease severity, liver cancer stage, receipt of HCC surveillance, and receipt of liver transplantation.
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