Hepatocellular carcinoma (HCC) is the sixth most common and third most deadly malignancy worldwide, carrying a mean survival rate without treatment of 6 to 20 months depending on stage.1 Fifty-seven percent of patients with liver cancer are diagnosed with regional or distant metastatic disease that carries 5-year relative survival rates of 10.7% and 3.1%, respectively.2 HCC arises most commonly from liver cirrhosis due to chronic hepatocyte injury, which may be mediated by viral hepatitis, alcoholism, and metabolic disease. Other less common causes include autoimmune disease, exposure to environmental hazards, and certain genetic diseases, such as α-1 antitrypsin deficiency and Wilson disease.
Multiple staging systems for HCC exist that incorporate some variation of the following features: size and invasion of the tumor, distant metastases, and liver function. Stage-directed treatments for HCC include ablation, embolization, resection, transplant, and systemic therapy, such as tyrosine kinase inhibitors, immunotherapies, and monoclonal antibodies. In addition to tumor/node/metastasis (TNM) staging, α-fetoprotein (AFP) is a diagnostic marker with prognostic value in HCC with higher levels correlating to higher tumor burden and a worse prognosis. With treatment, the 5-year survival rate for early stage HCC ranges from 60% to 80% but decreases significantly with higher stages.1 HCC screening in at-risk populations has accounted for > 40% of diagnoses since the practice became widely adopted, and earlier recognition has led to an improvement in survival even when adjusting for lead time bias.3
Systemic therapy for advanced disease continues to improve. Sorafenib remained the standard first-line systemic therapy since it was introduced in 2008.4 First-line therapy improved with immunotherapies. The phase 3 IMBrave150 trial comparing atezolizumab plus bevacizumab to sorafenib showed a median overall survival (OS) > 19 months with 7.7% of patients achieving a complete response.5 HIMALAYA, another phase 3 trial set for publication later this year, also reported promising results when a priming dose of the CTLA-4 inhibitor tremelimumab followed by durvalumab was compared with sorafenib.6
There has been a rise in incidence of HCC in the United States across all races and ethnicities, though Black, Hispanic, and Asian patients remain disproportionately affected. Subsequently, identifying causative biologic, socioeconomic, and cultural factors, as well as implicit bias in health care continues to be a topic of great interest.7-9 Using Surveillance, Epidemiology, and End Results (SEER) data, a number of large studies have found that Black patients with HCC were more likely to present with an advanced stage, less likely to receive curative intent treatment, and had significantly reduced survival compared with that of White patients.1,7-9 An analysis of 1117 patients by Rich and colleagues noted a 34% increased risk of death for Black patients with HCC compared with that of White patients, and other studies have shown about a 50% reduction in rate of liver transplantation for Black patients.10-12 Our study aimed to investigate potential disparities in incidence, etiology, AFP level at diagnosis, and outcomes of HCC in Black and White veterans managed at the Memphis Veterans Affairs Medical Center (VAMC) in Tennessee.
Methods
A single center retrospective chart review was conducted at the Memphis VAMC using the Computerized Patient Record System (CPRS) and the International Statistical Classification of Diseases, Tenth Revision (ICD-10) code C22.0 for HCC. Initial results were manually refined by prespecified criteria. Patients were included if they were diagnosed with HCC and received HCC treatment at the Memphis VAMC. Patients were excluded if HCC was not diagnosed histologically or clinically by imaging characteristics and AFP level, if the patient’s primary treatment was not provided at the Memphis VAMC, if they were lost to follow-up, or if race was not specified as either Black or White.
The following patient variables were examined: age, sex, comorbidities (alcohol or substance use disorder, cirrhosis, HIV), tumor stage, AFP, method of diagnosis, first-line treatments, systemic treatment, surgical options offered, and mortality. Staging was based on the American Joint Committee on Cancer TNM staging for HCC.13 Surgical options were recorded as resection or transplant. Patients who were offered treatment but lost to follow-up were excluded from the analysis.
Data Analysis
Our primary endpoint was identifying differences in OS among Memphis VAMC patients with HCC related to race. Kaplan-Meier analysis was used to investigate differences in OS and cumulative hazard ratio (HR) for death. Cox regression multivariate analysis further evaluated discrepancies among investigated patient variables, including age, race, alcohol, tobacco, or illicit drug use, HIV coinfection, and cirrhosis. Treatment factors were further defined by first-line treatment, systemic therapy, surgical resection, and transplant. χ2 analysis was used to investigate differences in treatment modalities.
Results
We identified 227 veterans, 95 Black and 132 White, between 2009 and 2021 meeting criteria for primary HCC treated at the Memphis VAMC. This study did not show a significant difference in OS between White and Black veterans (P = .24). Kaplan-Meier assessment showed OS was 1247 days (41 months) for Black veterans compared with 1032 days (34 months) for White veterans (Figure; Table 1).
Additionally, no significant difference was found between veterans for age or stage at diagnosis when stratified by race. The mean age of diagnosis for both groups was 65 years (P = .09). The mean TNM staging was 1.7 for White veterans vs 1.8 for Black veterans (P = .57). There was a significant increase in the AFP level at diagnosis for Black veterans (P = .001) (Table 2).
The most common initial treatment for both groups was transarterial chemoembolization and radiofrequency ablation with 68% of White and 64% of Black veterans receiving this therapy. There was no significant difference between who received systemic therapy.
However, we found significant differences by race for some forms of treatment. In our analysis, significant differences existed between those who did not receive any form of treatment as well as who received surgical resection and transplant. Among Black veterans, 11.6% received no treatment vs 6.1% for White veterans (P = .001). Only 2.1% of Black veterans underwent surgical resection vs 8.3% of White veterans (P = .046). Similarly, 13 (9.8%) White veterans vs 3 (3.2%) Black veterans received orthotopic liver transplantation (P = .052) in our cohort (eAppendix available at doi:10.12788/fp.0304). We found no differences in patient characteristics affecting OS, including alcohol use, tobacco use, illicit drug use, HIV coinfection, or liver cirrhosis (Table 3).