Geographic Variations of Potentially Curative Treatments for Hepatocellular Carcinoma in the United States: A SEER-Medicare Study

Restricted access

Background: Transplantation, surgical resection, radiofrequency ablation, and percutaneous ethanol injection are generally considered potentially curative treatments for patients with hepatocellular carcinoma (HCC). With the increasing incidence of HCC, it is critical to investigate geographic variations in curative treatments and their associations with survival among patients. Methods: A total of 6,782 patients with HCC during 2004 to 2011 were identified in the SEER-Medicare linked database and placed in quartiles based on the proportions undergoing potentially curative treatments per hospital referral region (HRR). Hierarchical Cox proportional hazards models were used to examine the association between regional potentially curative treatment patterns and survival across quartiles. Results: An average of 16.9% of patients with HCC underwent potentially curative treatments during 2004 to 2011, varying substantially from 0% to 34.5% across HRRs. Compared with patients residing in the lowest-quartile regions, those in the highest-quartile regions were more likely to be of other races (vs white or black), be infected with hepatitis B virus, and have more comorbidities. The 5-year survival was 4.7% in the lowest-quartile regions and 11.4% in the highest-quartile regions (P<.001). After controlling for confounders, patients in the highest-quartile regions had a lower risk of mortality (adjusted hazard ratio, 0.78; 95% CI, 0.72–0.85). Conclusions: Patients with HCC who resided in HRRs with higher proportions of potentially curative treatments had better survival. Given its proven survival benefits, prompt clinical and policy actions are needed to reduce variations in treatment utilization.

Submitted October 16, 2019; accepted for publication January 6, 2020.

Author contributions: Study concept: Cheng, Wang. Data analysis: Cheng, Hung. Manuscript preparation: Cheng, Hung. Critical revision: Hung, Wang. Study supervision: Cheng, Wang.

Disclosures: Dr. Wang has disclosed that he receives grant/research support from Genentech. The remaining authors have disclosed that they have not received any financial consideration from any person or organization to support the preparation, analysis, results, or discussion of this article.

Correspondence: En Cheng, MD, MSPH, Department of Chronic Disease Epidemiology, School of Public Health, Yale University, 60 College Street, New Haven, CT 06510. Email en.cheng@yale.edu

Supplementary Materials

    • Supplemental Materials (PDF 470.22 KB)
  • 1.

    Noone AM, Howlader N, Krapcho M, , eds. SEER Cancer Statistics Review, 1975-2015, National Cancer Institute. Bethesda, MD. Available at: https://seer.cancer.gov/csr/1975_2015/, based on November 2017 SEER data submission, posted to the SEER web site, April 2018. Accessed March 31, 2020.

  • 2.

    White DL, Thrift AP, Kanwal F, . Incidence of hepatocellular carcinoma in all 50 United States, from 2000 through 2012. Gastroenterology 2017;152:812820.e5.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 3.

    Bruix J, Reig M, Sherman M. Evidence-based diagnosis, staging, and treatment of patients with hepatocellular carcinoma. Gastroenterology 2016;150:835853.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4.

    European Association for the Study of the Liver. EASL clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol 2018;69:182236.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5.

    Heimbach JK, Kulik LM, Finn RS, . AASLD guidelines for the treatment of hepatocellular carcinoma. Hepatology 2018;67:358380.

  • 6.

    Fong ZV, Tanabe KK. The clinical management of hepatocellular carcinoma in the United States, Europe, and Asia: a comprehensive and evidence-based comparison and review. Cancer 2014;120:28242838.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 7.

    Cho YK, Kim JK, Kim MY, . Systematic review of randomized trials for hepatocellular carcinoma treated with percutaneous ablation therapies. Hepatology 2009;49:453459.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8.

    Lin S, Hoffmann K, Schemmer P. Treatment of hepatocellular carcinoma: a systematic review. Liver Cancer 2012;1:144158.

  • 9.

    Llovet JM, Bruix J. Systematic review of randomized trials for unresectable hepatocellular carcinoma: chemoembolization improves survival. Hepatology 2003;37:429442.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10.

    Simonetti RG, Liberati A, Angiolini C, . Treatment of hepatocellular carcinoma: a systematic review of randomized controlled trials. Ann Oncol 1997;8:117136.

  • 11.

    El-Serag HB, Siegel AB, Davila JA, . Treatment and outcomes of treating of hepatocellular carcinoma among Medicare recipients in the United States: a population-based study. J Hepatol 2006;44:158166.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12.

    Sonnenday CJ, Dimick JB, Schulick RD, . Racial and geographic disparities in the utilization of surgical therapy for hepatocellular carcinoma. J Gastrointest Surg 2007;11:16361646.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13.

    Altekruse SF, Henley SJ, Cucinelli JE, . Changing hepatocellular carcinoma incidence and liver cancer mortality rates in the United States. Am J Gastroenterol 2014;109:542553.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14.

    Franco RA, Fan Y, Jarosek S, . Racial and geographic disparities in hepatocellular carcinoma outcomes. Am J Prev Med 2018;55(Suppl 1):S4048.

  • 15.

    Gornick ME, Warren JL, Eggers PW, . Thirty years of Medicare: impact on the covered population. Health Care Financ Rev 1996;18:179237.

  • 16.

    Warren JL, Klabunde CN, Schrag D, . Overview of the SEER-Medicare data: content, research applications, and generalizability to the United States elderly population. Med Care 2002;40(8 Suppl):IV-318.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 17.

    Dartmouth Atlas Project. Understanding geographic variations in health care. Accessed October 9, 2019. Available at: http://www.dartmouthatlas.org

    • Export Citation
  • 18.

    Llovet JM, Schwartz M, Mazzaferro V. Resection and liver transplantation for hepatocellular carcinoma. Semin Liver Dis 2005;25:181200.

  • 19.

    Tsuzuki T, Sugioka A, Ueda M, . Hepatic resection for hepatocellular carcinoma. Surgery 1990;107:511520.

  • 20.

    Chirica M, Scatton O, Massault PP, . Treatment of stage IVA hepatocellular carcinoma: should we reappraise the role of surgery? Arch Surg 2008;143:538543.

  • 21.

    Hanazaki K, Kajikawa S, Shimozawa N, . A 15-year retrospective study of hepatic resection for stage IV-A hepatocellular carcinoma shows value in hepatitis B negative patients. Am J Surg 2002;183:8994.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 22.

    Poon RT, Fan ST, Ng IO, . Prognosis after hepatic resection for stage IVA hepatocellular carcinoma: a need for reclassification. Ann Surg 2003;237:376383.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 23.

    Shimada M, Takenaka K, Kawahara N, . Surgical treatment strategy for patients with stage IV hepatocellular carcinoma. Surgery 1996;119:517522.

  • 24.

    Elixhauser A, Steiner C, Harris DR, . Comorbidity measures for use with administrative data. Med Care 1998;36:827.

  • 25.

    Islami F, Miller KD, Siegel RL, . Disparities in liver cancer occurrence in the United States by race/ethnicity and state. CA Cancer J Clin 2017;67:273289.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 26.

    Cronin KA, Lake AJ, Scott S, . Annual report to the nation on the status of cancer, part I: national cancer statistics. Cancer 2018;124:27852800.

  • 27.

    Lauerer M, Kaiser K, Nagel E. Organ transplantation in the face of donor shortage: ethical implications with a focus on liver allocation. Visc Med 2016;32:278285.

  • 28.

    New Mexico Department of Health. The State of Health in New Mexico 2018. Accessed October 9, 2019. Available at: https://nmhealth.org/publication/view/report/4442/

    • Export Citation
  • 29.

    U.S. News & World Report. Best States 2019. Accessed October 9, 2019. Available at: https://www.usnews.com/news/best-states/

    • Export Citation
  • 30.

    United States Census Bureau. Population and Housing Unit Estimates. Accessed October 9, 2019. Available at: https://www.census.gov/programs-surveys/popest.html

    • Export Citation
  • 31.

    Aizer AA, Chen MH, McCarthy EP, . Marital status and survival in patients with cancer. J Clin Oncol 2013;31:38693876.

  • 32.

    Galati G, Dell’Unto C, Vespasiani-Gentilucci U, . Hepatocellular carcinoma in alcoholic liver disease: current management and recent advances. Rev Recent Clin Trials 2016;11:238252.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 33.

    Kuo KL, Stenehjem D, Albright F, . Treatment patterns and outcomes in patients with hepatocellular carcinoma stratified by stage-guided treatment categories. J Natl Compr Canc Netw 2015;13:987994.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 34.

    Poon RT, Fan ST, Lo CM, . Long-term prognosis after resection of hepatocellular carcinoma associated with hepatitis B-related cirrhosis. J Clin Oncol 2000;18:10941101.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 35.

    Chen VL, Le AK, Kim NG, . Effects of cirrhosis on short-term and long-term survival of patients with hepatitis B-related hepatocellular carcinoma. Clin Gastroenterol Hepatol 2016;14:887895.e1.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 36.

    Nathan H, Hyder O, Mayo SC, . Surgical therapy for early hepatocellular carcinoma in the modern era: a 10-year SEER-Medicare analysis. Ann Surg 2013;258:10221027.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 37.

    Centers for Medicare & Medicaid Services. 2019 Medicare Trustees Report. Accessed October 9, 2019. Available at: https://www.cms.gov/Research-Statistics-Data-and-Systems/Statistics-Trends-and-Reports/ReportsTrustFunds/Downloads/TR2019.pdf

All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 375 375 320
PDF Downloads 104 104 83
EPUB Downloads 0 0 0