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Original Article |

Racial Discrepancies in the Outcome of Patients With Hepatocellular Carcinoma FREE

Lawrence E. Harrison, MD; Trevor Reichman, MD, PhD; Baburao Koneru, MD; Adrian Fisher, MD; Dorian Wilson, MD; Andrew Dela Torre, MD; Arun Samanta, MD; Maria Korogodsky, RN
[+] Author Affiliations

From the Department of Surgery, UMDNJ[[ndash]]New Jersey Medical School, Newark.


Arch Surg. 2004;139(9):992-996. doi:10.1001/archsurg.139.9.992.
Text Size: A A A
Published online

Hypothesis  There is a marked variation in the outcome of patients with hepatocellular carcinoma with respect to race and ethnicity. Rates among African American and Hispanic individuals are elevated as compared with those among white individuals.

Design  Retrospective review of a prospective database. Demographic information, clinical staging, and other defining factors, including the absence or presence of hepatitis, cirrhosis, and alcohol abuse, were analyzed by patient interviews and review of the medical record.

Setting  Urban tertiary referral teaching hospital.

Patients  Patients diagnosed as having hepatocellular carcinoma between July 1997 and June 2003 (N = 264).

Main Outcome Measure  Overall survival rates.

Results  Based on multivariate analysis, race was identified as an independent predictor of survival. While there was no difference in the distribution of patient or tumor characteristics between the 2 groups, African American/Hispanic patients had a 5-year survival rate of 12%, which was significantly lower than that of white patients (50%; P = .001).

Conclusions  This study demonstrates a significant discrepancy in overall survival of African American/Hispanic patients as compared with that of white patients. The reason for this difference cannot be explained by patient or tumor characteristics or completely by treatment allocation. These data suggest that there may be socioeconomic, biological, and/or cultural determinants contributing to this observed difference in outcome.

Figures in this Article

Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world and accounts for approximately half a million deaths worldwide per year.1 Despite its overall high prevalence, the geographic distribution of HCC cases varies widely, with rates of 30 per 100 000 men reported in high-risk regions, such as sub-Saharan Africa and Southeast Asia, to less than 2 per 100 000 in Northern Europe and the United States.2 Although more frequently diagnosed in the endemic regions than in the West, the incidence of HCC is increasing in the United States and in Europe.3,4 Given the increased prevalence of HCC in high-risk regions, it is not surprising that most large clinical studies have arisen from non-Western medical centers. However, the etiologic factors for HCC are different in the East as compared with the West,5 and conclusions based on these non-Western studies may not appropriately reflect the patients treated in Western medical centers.

While there is a documented rise in the incidence of HCC in the United States, this increase is not uniform throughout the population. There is a marked variation in the incidence of HCC with respect to race and ethnicity, with rates among African American and Hispanic individuals being elevated as compared with those among white individuals.6,7 Importantly, discrepancies in overall cancer survival rates among white individuals and minorities in the United States have been reported, and this difference in survival rates has been attributed to a variety of factors, including disparities in treatment, rates of death due to other causes, and/or biological behavior of the cancer itself.810

The purpose of this study was to evaluate the difference in survival of African American and Hispanic patients diagnosed as having HCC as compared with that of white patients treated at the same institution. We found that patient race was an independent predictor of survival by multivariate analysis, and despite no statistical differences in patient or tumor characteristics, the overall survival of African American and Hispanic patients was significantly lower than that of white patients.

STUDY POPULATION

A review of a prospective database for gastrointestinal malignancies at University Hospital (Newark, NJ) between July 1997 and June 2003 identified 264 patients diagnosed as having HCC. Demographic information, clinical staging, and other defining factors, including the absence or presence of hepatitis, cirrhosis, and alcohol abuse, were analyzed by patient interviews and review of the medical record. Standard laboratory data were also quantitated. Tumor staging was carried out using the criteria set forth by the American Joint Committee on Cancer Cancer Staging Manual.11

STATISTICAL ANALYSIS

Continuous variables were presented as median (range). All demographic data, laboratory values, and pathologic data were analyzed for significance of their ability to predict survival by univariate and multivariate analysis. P values were calculated using either χ2 test or Fisher exact test where appropriate. A P value greater than .05 was considered to be significant. Values found to be significant by univariate analysis were further analyzed by multiple regression analysis using the SPSS statistical program (SPSS Inc, Chicago, Ill). Survival was also analyzed by the Kaplan-Meier method, and curves were compared using the Cox-Mantel log-rank test.

ANALYSIS OF ENTIRE PATIENT POPULATION

During the 6-year study period, 264 patients with a diagnosis of HCC were identified (men, n = 209; women, n = 55), with a median age of 59 years (range, 25-92 years). Of the 264 patients, 61% were white, 13% Hispanic, 18% African American, and 8% other (Figure 1). The overall 5-year survival of the entire patient population was 38% (median survival, 16.6 months) (Figure 2) with a median follow-up of 10 months (range, 1-63 months). Table 1 summarizes the factors predicting survival, with patient race, pretreatment serum α-fetoprotein (AFP) levels, and palliative vs curative therapy as independent predictors of survival by multivariate analysis.

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Figure 1.

Distribution of racial background.

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Figure 2.

Overall survival of the entire series.

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Table Graphic Jump LocationTable 1. Factors Predicting Survival

Of the 264 patients, 12 patients were identified as being of Asian descent and 8 patients as having other racial or ethnic backgrounds. Based on the finding that race was an independent predictor of survival, these 20 patients were excluded from the subsequent analysis comparing African American/Hispanic patients (n = 83) with white patients (n = 161).

COMPARISON OF RACIAL GROUPS

The risk factors for cirrhosis are summarized in Table 2, with 144 (59%) of all patients having hepatitis B and/or C while 36% of patients had abused alcohol. Hepatic parenchymal function was assessed by the Child-Turcotte-Pugh class system, and of those patients with documented cirrhosis, 18% were diagnosed as having class A, 27% class B, and 22% class C. Tumor size and staging of disease are summarized in Table 3. Most patients were diagnosed as having a single lesion (n = 145). The median size of the tumors in this cohort was 4 cm (range, 1-16 cm). There was no difference in the distribution of patient or tumor factors between African American/Hispanic patients and white patients. Distribution of AFP levels was evaluated based on race. White patients had a higher percentage of AFP levels less than 10 ng/mL, whereas African American/Hispanic patients had a higher percentage of AFP levels greater than 3000 ng/mL (Figure 3).

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Figure 3.

Distribution of pretreatment α-fetoprotein levels.

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TREATMENT CHARACTERISTICS

Treatment of patients was divided into surgical (eg, resection or transplant), nonsurgical intervention, and palliative care. Seventy-four patients were not appropriate candidates for any of the offered treatments and were treated symptomatically. One hundred two patients underwent nonsurgical interventions, which included arterial embolization (n = 85), ethanol injection (n = 6), and radiofrequency ablation (n = 53). Most patients underwent multiple sessions of nonsurgical interventions, often using multiple modalities. The total number of surgical patients was 68, with 20 of those patients undergoing resection and 48 receiving orthotopic liver transplantation. The distribution of the individual therapies between African American/Hispanic patients and white patients was equivalent, with the exception of 24% of white patients undergoing orthotopic liver transplantation as compared with only 12% of African American/Hispanic patients (Figure 4) (P = .05).

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Figure 4.

Distribution of therapies.

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SURVIVAL DATA

The 5-year overall survival rate for white patients was 50% (median survival, not reached), as compared with 12% for the African American/Hispanic group (median survival, 9.2 months; P = .001) (Figure 5). Based on our finding that more white patients underwent transplantation as compared with African American/Hispanic patients in this series, the survival analysis was repeated excluding patients who underwent transplantation, and the significant difference in survival between white patients (n = 123) and African American/Hispanic patients (n = 73) was maintained (P = .05) (Figure 6).

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Figure 5.

Overall survival by race.

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Figure 6.

Overall survival by race, excluding patients undergoing transplantation.

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Survival by therapy was next evaluated and is represented in Table 4. There was no difference in outcome of patients undergoing supportive care, resection, or transplantation. There was, however, a trend in outcome between African American/Hispanic patients (5-year survival, 0%; median survival, 9.2 months) and white patients (5-year survival, 35%; median survival, 11.6 months) in the group undergoing nonsurgical interventions (P = .06).

Overall survival was next calculated based on stage at initial examination. Patients were grouped as early stage (stages I or II) or late stage (stages IIIA-C or IV). There was a significant difference in 5-year survival between African American/Hispanic patients (29%; median survival, 16.9 months) and white patients (70%; median survival, not reached; P = .01) in the early-stage group. No differences in survival were detected in patients with late-stage disease (Figure 7).

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Figure 7.

Overall survival: early vs late stage.

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While the incidence of HCC in the United States continues to increase,3 there is a marked variation with respect to race and ethnicity.6,12 Shea et al6 report that while the incidence of HCC in Florida was comparable with that in the rest of the United States, the age-adjusted rate for HCC in African American and Hispanic patients was nearly twice that of white patients. Similar differences in the rate of HCC between African American patients and white patients have also been observed in New Jersey (data not shown). In addition to differences in incidence, ethnicity may also predict outcome in patients with HCC. Chin et al13 compared the outcomes of Asian patients and those of other races diagnosed as having HCC at a Western institution. They reported that ethnic status was an independent predictor of outcome, with patients of other races having a better survival rate as compared with that of Asian patients. On the basis of these data and the fact that Asian patients contributed only 5% to our series, we elected to exclude patients who were not white, African American, or Hispanic from the analysis to avoid confounding variables.

We observed that while African American and Hispanic patients had a similar survival rate, this was significantly inferior to that of white patients diagnosed at 1 institution during the same period. This discrepancy in survival based on race has been documented in other tumor sites. Bach et al9 reviewed the literature and analyzed 189 877 white patients and 32 004 black patients with 14 different cancers. Compared with white patients, black patients had an overall and cancer-specific excess risk of death. In addition, of the 14 different cancer sites, black patients were at a significantly higher risk of death from breast, uterine, and bladder cancers. This difference in survival rate in minority populations has been attributed to a variety of factors, including disparities in early diagnosis and treatment, additional comorbidities, and/or the biological behavior of the cancer itself. Interestingly, in many series, the differences in survival persist even after adjustments for both clinical and socioeconomic characteristics.1416

In terms of access to treatment as a factor contributing to the discrepancy in survival in our series, there was no difference in the distribution of treatment between the 2 groups, with the exception that 24% of white patients underwent orthotopic liver transplantation as compared with only 12% of African American/Hispanic patients. The reason for this discrepancy is unclear and may reflect comorbid and/or social issues not identified by this study, as well as issues relating to limited access to medical therapy in minority groups. When survival analysis was repeated excluding all patients who underwent transplantation, the significant difference in overall survival between white patients and African American/Hispanic patients was maintained. Therefore, in addition to the discrepancy observed in hepatic transplantation, other factors may play a role in the differences in survival. Unfortunately, it was beyond the scope of this study to evaluate comorbid conditions or financial and social factors relating to health care access and treatment. However, the lack of difference in the distribution of tumor stage or size at initial examination among racial groups may indirectly support the hypothesis that access to medical care was not a major factor in the survival differences noted.

In addition to differences in comorbid disease and socioeconomic issues, a third possible factor contributing to the observed differences in outcome may be based on tumor biological features or the host genetic defense mechanisms. Supporting this concept is the fact that despite similar distribution of tumor stage between white patients and African American/Hispanic patients (Table 2), a significant difference in survival was noted between the 2 groups with early-stage disease. Perhaps this suggests that in stage I and II disease, when survival can be affected by treatment, tumors in African American/Hispanic patients are more aggressive or there is some inability of the host to tolerate the tumor burden. In terms of host response, it has been suggested that African American and Hispanic individuals may have an increased susceptibility to hepatocellular injury.17,18 We also noted that AFP levels were significantly higher in African American/Hispanic patients as compared with those in white patients. α-Fetoprotein levels have been noted to be independent prognostic factors for patients with HCC and may represent a marker for tumor biological characteristics.19

In summary, this study demonstrates a significant discrepancy in overall survival of African American/Hispanic patients as compared with that of white patients, even when discrepancies in transplantation rates are considered. The reason for this difference cannot be explained by patient or tumor characteristics or completely by treatment allocation. Additional studies are needed to clarify the socioeconomic, biological, and cultural determinants in this type of tumor.

Correspondence: Lawrence E. Harrison, MD, Department of Surgery, Division of Surgical Oncology, UMDNJ–New Jersey Medical School, 185 S Orange Ave, MSB G588, Newark, NJ 07103 (l.harrison@umdnj.edu).

Accepted for publication January 5, 2004.

El Serag  HB Hepatocellular carcinoma: an epidemiologic view [review]. J Clin Gastroenterol. 2002;35 (suppl 2) S72- S78
PubMed Link to Article
Farmer  DGRosove  MHShaked  ABusuttil  RW Current treatment modalities for hepatocellular carcinoma. Ann Surg. 1994;219236- 247
PubMed Link to Article
El Serag  HBMason  AC Rising incidence of hepatocellular carcinoma in the United States. N Engl J Med. 1999;340745- 750
PubMed Link to Article
Taylor-Robinson  SDFoster  GRArora  SHargreaves  SThomas  HC Increase in primary liver cancer in the UK, 1979-1994. Lancet. 1997;3501142- 1143
PubMed Link to Article
Stuart  KEAnand  AJJenkins  RL Hepatocellular carcinoma in the United States. Cancer. 1996;772217- 2222
PubMed Link to Article
Shea  KAFleming  LEWilkinson  JDWohler-Torres  BMcKinnon  JA Hepatocellular carcinoma incidence in Florida. Cancer. 2001;911046- 1051
PubMed Link to Article
Trapido  EJMcCoy  CBStein  NSEngel  SZavertnik  JJComerford  M Epidemiology of cancer among Hispanic males. Cancer. 1990;651657- 1662
PubMed Link to Article
Clegg  LXLi  FPHankey  BFChu  KEdwards  BK Cancer survival among US whites and minorities: a SEER (Surveillance, Epidemiology, and End Results) Program population-based study. Arch Intern Med. 2002;1621985- 1993
PubMed Link to Article
Bach  PBSchrag  DBrawley  OWGalaznik  AYakren  SBegg  CB Survival of blacks and whites after a cancer diagnosis. JAMA. 2002;2872106- 2113
PubMed Link to Article
Parker  SLDavis  KJWingo  PARies  LAHeath Jr  CW Cancer statistics by race and ethnicity. CA Cancer J Clin. 1998;4831- 48
PubMed Link to Article
Greene  FLPage  DLFleming  ID  et al. American Joint Committee on Cancer, Cancer Staging Manual. 6th ed. New York, NY Springer-Verlag2002;
PubMed
Davila  JAPetersena  NJNeson  HAEl Serag  HB Geographic variation within the United States in the incidence of hepatocellular carcinoma. J Clin Epidemiol. 2003;56487- 493
PubMed Link to Article
Chin  PLChu  DZClarke  KGOdom-Maryon  TYen  YWagman  LD Ethnic differences in the behavior of hepatocellular carcinoma. Cancer. 1999;851931- 1936
PubMed Link to Article
Eley  JWHill  HAChen  VW  et al.  Racial differences in survival from breast cancer: results of the National Cancer Institute Black/White Cancer Survival Study. JAMA. 1994;272947- 954
PubMed Link to Article
Howard  JHankey  BFGreenberg  RS  et al.  A collaborative study of differences in the survival rates of black patients and white patients with cancer. Cancer. 1992;692349- 2360
PubMed Link to Article
Breen  NWesley  MNMerrill  RMJohnson  K The relationship of socio-economic status and access to minimum expected therapy among female breast cancer patients in the National Cancer Institute Black-White Cancer Survival Study. Ethn Dis. 1999;9111- 125
PubMed
Stewart  SH Racial and ethnic differences in alcohol-associated aspartate aminotransferase and gamma-glutamyltransferase elevation. Arch Intern Med. 2002;1622236- 2239
PubMed Link to Article
Singh  GKHoyert  DL Social epidemiology of chronic liver disease and cirrhosis mortality in the United States, 1935-1997. Hum Biol. 2000;72801- 820
PubMed
Fong  YSun  RLJarnagin  WBlumgart  LH An analysis of 412 cases of hepatocellular carcinoma at a Western center. Ann Surg. 1999;229790- 799
PubMed Link to Article

Figures

Place holder to copy figure label and caption
Figure 1.

Distribution of racial background.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 2.

Overall survival of the entire series.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 3.

Distribution of pretreatment α-fetoprotein levels.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 4.

Distribution of therapies.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 5.

Overall survival by race.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 6.

Overall survival by race, excluding patients undergoing transplantation.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 7.

Overall survival: early vs late stage.

Graphic Jump Location

References

El Serag  HB Hepatocellular carcinoma: an epidemiologic view [review]. J Clin Gastroenterol. 2002;35 (suppl 2) S72- S78
PubMed Link to Article
Farmer  DGRosove  MHShaked  ABusuttil  RW Current treatment modalities for hepatocellular carcinoma. Ann Surg. 1994;219236- 247
PubMed Link to Article
El Serag  HBMason  AC Rising incidence of hepatocellular carcinoma in the United States. N Engl J Med. 1999;340745- 750
PubMed Link to Article
Taylor-Robinson  SDFoster  GRArora  SHargreaves  SThomas  HC Increase in primary liver cancer in the UK, 1979-1994. Lancet. 1997;3501142- 1143
PubMed Link to Article
Stuart  KEAnand  AJJenkins  RL Hepatocellular carcinoma in the United States. Cancer. 1996;772217- 2222
PubMed Link to Article
Shea  KAFleming  LEWilkinson  JDWohler-Torres  BMcKinnon  JA Hepatocellular carcinoma incidence in Florida. Cancer. 2001;911046- 1051
PubMed Link to Article
Trapido  EJMcCoy  CBStein  NSEngel  SZavertnik  JJComerford  M Epidemiology of cancer among Hispanic males. Cancer. 1990;651657- 1662
PubMed Link to Article
Clegg  LXLi  FPHankey  BFChu  KEdwards  BK Cancer survival among US whites and minorities: a SEER (Surveillance, Epidemiology, and End Results) Program population-based study. Arch Intern Med. 2002;1621985- 1993
PubMed Link to Article
Bach  PBSchrag  DBrawley  OWGalaznik  AYakren  SBegg  CB Survival of blacks and whites after a cancer diagnosis. JAMA. 2002;2872106- 2113
PubMed Link to Article
Parker  SLDavis  KJWingo  PARies  LAHeath Jr  CW Cancer statistics by race and ethnicity. CA Cancer J Clin. 1998;4831- 48
PubMed Link to Article
Greene  FLPage  DLFleming  ID  et al. American Joint Committee on Cancer, Cancer Staging Manual. 6th ed. New York, NY Springer-Verlag2002;
PubMed
Davila  JAPetersena  NJNeson  HAEl Serag  HB Geographic variation within the United States in the incidence of hepatocellular carcinoma. J Clin Epidemiol. 2003;56487- 493
PubMed Link to Article
Chin  PLChu  DZClarke  KGOdom-Maryon  TYen  YWagman  LD Ethnic differences in the behavior of hepatocellular carcinoma. Cancer. 1999;851931- 1936
PubMed Link to Article
Eley  JWHill  HAChen  VW  et al.  Racial differences in survival from breast cancer: results of the National Cancer Institute Black/White Cancer Survival Study. JAMA. 1994;272947- 954
PubMed Link to Article
Howard  JHankey  BFGreenberg  RS  et al.  A collaborative study of differences in the survival rates of black patients and white patients with cancer. Cancer. 1992;692349- 2360
PubMed Link to Article
Breen  NWesley  MNMerrill  RMJohnson  K The relationship of socio-economic status and access to minimum expected therapy among female breast cancer patients in the National Cancer Institute Black-White Cancer Survival Study. Ethn Dis. 1999;9111- 125
PubMed
Stewart  SH Racial and ethnic differences in alcohol-associated aspartate aminotransferase and gamma-glutamyltransferase elevation. Arch Intern Med. 2002;1622236- 2239
PubMed Link to Article
Singh  GKHoyert  DL Social epidemiology of chronic liver disease and cirrhosis mortality in the United States, 1935-1997. Hum Biol. 2000;72801- 820
PubMed
Fong  YSun  RLJarnagin  WBlumgart  LH An analysis of 412 cases of hepatocellular carcinoma at a Western center. Ann Surg. 1999;229790- 799
PubMed Link to Article

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