Liver Cancer: Epidemiology and Health Disparities Andrea Goldstein NP, MS, MPH Scientific Director Onyx Pharmaceuticals
1. Bosch FX, et al. Gastroenterology. 2004;127(5 suppl 1):S5-S16. 2. American Cancer Society: Cancer Facts & Figures 2013. Atlanta, GA. 3. American Cancer Society: Global Cancer Facts & Figures 2007. Atlanta, GA. Available at http://www.cancer.org/acs/groups/content/@nho/documents/document/globalfactsandfigures2007rev2p.pdf. Accessed April 10, 2013 Epidemiology Primary Liver Cancer Hepatocellular cancer (HCC) accounts for 70% 85% of primary liver malignancies worldwide 3 More common in men than women (> 2:1 ratio) 1 Incidence Mortality Fifth leading cause of cancer in men and eighth leading cause of cancer in women globally: 560,000 new annual cases 1 28,720* (21,370 in men and 7,350 in women) new cases in United States in 2012 2 Third leading cause of cancer-related death globally 3 Fifth leading cause of cancer-related death in men and ninth in women in United States 2 *Estimated; includes intrahepatic bile duct cancers.
Epidemiology Primary Liver Cancer In the past 30 years the incidence and mortality rates for HCC in the United States have more than doubled 1 Rising rates of Hepatitis C viral infection (HCV) Migration from Hepatitis B (HBV) endemic areas Rising rates of obesity in the United States which is the leading cause of NAFLD and NASH 1 El-Serag HB et al, Ann Intern Med 2003
HCC Epidemiology Worldwide Incidence of Hepatocellular Carcinoma Worldwide Incidence of Hepatocellular Carcinoma El-Serag HB, Gastroenterology 2004 High (> 30:100,000) Intermediate (3-30:100,000) Low or data unavailable (< 3:100,000)
HCC Epidemiology Incidence, global Eastern Asia South-Eastern Asia Middle Africa Western Africa Southern Africa Melanesia Southern Europe Micronesia/Polynesia Northern Africa Central America Western Europe Eastern Africa North America Caribbean South America Australia/New Zealand Central & Eastern Europe Western Asia Northern Europe South-Central Asia Global Variation in Primary Liver Cancer Incidence Adapted from Jemal A, et al. Ca Cancer J Clin. 2011;61:69-90. Females Males 0 10 20 30 40 Age Standardized Incidence per 100,000
Regional Variations in HCC-related Mortality HCC Epidemiology Regional Variations in HCC-related Mortality Mortality Rate / 100,000 Age-Adjusted 5.24 to 6.12 (6) 4.49 to 5.24 (5) 4.28 to 4.49 (5) 4.09 to 4.28 (5) 3.94 to 4.09 (5) 3.75 to 3.94 (6) 3.50 to 3.75 (5) 3.19 to 3.50 (5) 2.74 to 3.19 (5) 2.21 to 2.74 (4) Sparse Data (0) El-Serag HB, Gastroenterology 2004
HCC Epidemiology Incidence, United States Incidence 1* Deaths 1* 9 th leading cause of cancer deaths 21,370 7,350 Females Males 6,570 13,980 Median age at diagnosis 5 th leading cause of cancer deaths 64 years 2 Highest mean annual % change in incidence rate in persons 50-59 years 2 Increasing incidence of HCC likely caused by 3 Aging of persons who acquired HCV during 1960s Improved survival of cirrhotic patients Increasing obesity and diabetes rates *Estimated; includes intrahepatic bile duct cancers. 1. American Cancer Society: Cancer Facts & Figures 2012. Atlanta, GA. 2. Centers for Disease Control and Prevention. Morbidity and Mortality Weekly Report. 2010;59:517-20. 3. McGlynn KA, et al. Cancer Epidemiol Biomarkers Prev. 2006;15:1198-1203.
Epidemiology HCC risk factors Nonalcoholic Steatohepatitis Alcohol Autoimmune factors Hepatitis C Inherited factors Hepatitis B Aflatoxin B1 Adapted from Farazi PA, et al. Nat Rev Cancer. 2006;6:674-87; Shariff MI, et al. Exp Rev Gastroenterol Hepatol. 2009;3(4):353-67.
HCC Epidemiology Racial Incidence Rates For HCC In The United States Age-adjusted incidence rate per 100,000 9 8 6 4 2 1 2.5 White Black Other (Asian) 6 1.1 2.5 5.2 1.1 2.6 6.3 1.3 2.9 6.6 1.4 3.4 7.2 1.7 3.7 7.2 1.9 3.9 8.4 4. 6 2.3 7.9 2.5 5 8 0 76-78 79-81 82-84 85-87 88-90 91-93 94-9697-992000-02 El-Serag HB et al, Ann Intern Med 2003 Year
HCC Epidemiology Incidence of HCC in Whites (Hispanics and non-hispanics) 9 8 White Non-Hispanic White Hispanic Age-adjusted incidence rate per 100,000 6 4 2 0 1993 1995 1997 1999 2001 Year 2003
HCC Epidemiology Racial Distribution of detected HCC in the United States 3000 Number of cases 2500 2000 1500 1000 500 0 Asian Black White 75-77 78-80 81-83 84-86 87-89 90-92 93-95 96-98 Year El-Serag HB, Mason A, N Engl J Med 1999
HCV-Related HCC and Ethnicity in the US HCV-Related HCC and Ethnicity in the US Ethnicity of patients with HCC and serological testing for HBsAg and anti-hcv, in absolute numbers White (n=410) HBsAg Neither Anti-HCV Neither Black (n=95) HBsAg Asian (n=107) Both markers Neither Both markers Both markers Anti-HCV HBsAg Di Bisceglie AM et al. Am J Gastroenterol 2003; 98:2060 Anti-HCV
Future Trends in HCC Incidence HCC Epidemiology Future Trends in HCC Incidence Distribution of risk factors among HCC cases HCV 24% to 60% NASH/NAFLD 13% up to 50% Prevalence of risk factors in the general population HCV 2% Obesity 30%, overweight 60% HBV 0.4%
HCC Epidemiology Rate of Chronic HCV Infection in the US Highest Among Young African-American Adults % Anti-HCV Positive 7 6 5 4 3 2 1 0 African-American Hispanic Caucasian 6-11 12-19 20-29 30-39 40-49 50-59 60-69 >70 Age Group (years) Third National Health & Nutrition Examination Survey, 1988-1994 CDC, MMWR 1998
El-Serag HB et al, Archives of Internal Medicine (no. (October 8, 2007) The Estimated Annual Percentage Change (EAPC) in Hepatocellular Carcinoma Incidence by Race/Ethnicity and Sex During the 1992-2002 EAPC (95% Confidence Interval) Race Ethnicity EAPC (95%) Confidence interval (n=14,210) Hispanic Male Female White non-hispanic Male Female Black Male Female Asian/Pacific Islander Male Female 4.7(2.8-6.6) 3.5 (1.4 to 5.8) 6.8 (3.6 to 10.1) 4.3 (2.9 to 5.8) 4.0 (2.4 to 5.6) 3.6 (1.9 to 5.3) 4.3 (2.7 to 6.0) 5.4 (3.5 to 7.2) 1.7 (-2.1 to 5.8) 0.6 (-0.8 to 2.0) 0.7 (-0.8 to 202) 0.7 (-1.2 to 2.8)
HCC Epidemiology Effect of treatment on survival Most Patients Have Advanced Disease at Diagnosis 1 Disease Stage and Treatment Status 1-Year Survival a (%) Localized Treated 83 Not Treated 38 Regional Treated 60 Not Treated 21 Distant Treated 30 Not Treated 6 Liver Transplantation, Liver Resection, RFA Locally ablative or regional therapy to tumor Systemic treatment, clinical trials or palliative therapy a 2003-2004, diagnosis years. 1.Davila JA, et al. Hepatology. 2010;52:132-41. 2. Altekruse SF, et al. J Clin Oncol. 2009;27:1485-91.
Outcomes: Dependent on treatment eligibility at time of diagnosis Early diagnosis is better for HCC 5 year survival for untreated HCC is 6-7% 1-2 4-year survival is 74% for patients who diagnosed early enough for liver transplantation 3 Improvement in survival have not been uniform, there are racial/minority and insurance related disparities 1 Liu JH et al., Ann Surg Oncol. 2004:11:298-303 2 El-Serag HB et al., Hepatology. 2001;33:62-65 3 Mazzaferro V et al., N Engl J Med. 1996;334:693-699
Survival by treatment of liver cancer in patients who had non-metastatic disease (data from 1998-2004, N=8392) Artinyan A et al. Cancer, March 2010, 1367-1377
Metastatic Liver Cancer (survival by race/ethnicity 1973-2004, n=17,209) Cumulative survival Artinyan A et al., Cancer, March 2010, 1367-1377 Months
Rate of Intervention by Race/Ethnicity for Patients who had non-metastatic disease Treatment White Asian/PI Hispanic Black No surgery 2563 (62%) 1048 (55%) 837 (67%) 672 (69%) Ablation 396 (10%) 232 (12%) 109 (9%) 93 (10%) Resection 691 (17%) 469 (25%) 138 (11%) 145 (15%) Transplantation 515 (12%) 148 (8%) 157 (13%) 64 (7%) Artinyan A et al., Cancer, March 2010, 1367-1377
Outcomes by Race for Liver Resection or Transplantation Artinyan A et al., Cancer, March 2010, 1367-1377
Cumulative Overall Survival by Race for patients who underwent Liver Transplantation (UNOS data October 1987-February 2008 Artinyan A et al., Cancer, March 2010, 1367-1377
Insurance Disparities with Liver Transplantation Black patients are significantly less likely to receive a liver transplant than whites (up 30X less likely, OR ratio=0.03, 95% CI 0.0-0.37) 1 Hispanics and Asian/Pacific Islanders were also less likely to receive a liver transplant but they were not statistically significant compared to whites (OR ratio=0.42, 95% CI 0.09-2.08; OR=0.33, 95% CI 0.02-4.44) respectively 1 Patients with Private Insurance were more likely to receive a liver transplant that those patients with Medicaid 1-2 Black and Hispanic patients and Medicaid patients presented with HCC at a more advanced stage of disease leading to a poorer prognosis and survival 1 Those patients who did not receive a liver transplant were 3 times more likely to die 1 1.Yu JC., et al., Cancer, April 1, 2010, 1801-1808 2. Artinyan A et al., Cancer, March 2010, 1367-1377 3. Robbins AS et al., Cancer, October 1, 2011, 4531-4539
Summary We have seen a doubling in the prevalence of HCC in the United States over the past 30 years Early detection provides the best option for survival as it allows patients to receive a surgical intervention (Liver Transplant and Liver Resection) HCC is most prevalent in Asian Americans followed by African Americans (Blacks) and then Whites We are seeing a dramatic increase in Hispanics with HCC compared to Whites The majority of all racial/ethic groups are diagnosed at an advanced stage of disease leading to a poor prognosis African Americans and Asian Americans are less likely to receive liver transplantation than other racial/ethic minorities African Americans have the worst survival when diagnosed with HCC and poorest survival even after LT and Liver Resection
you are all new healthcare providers, so now you have the power and potential impact as clinicians to improve the lives of others through primary care, through education, through health-promotion and through patient advocacy there are people, rather patients out there who need you I ask you to take care of the most vulnerable among us. Dr. Randy Caine