The incidence of hepatocellular carcinoma (HCC) in the United States has historically been lower than that of other countries, but studies have shown that rates of the disease have increased substantially in recent decades. In addition, primary liver cancer mortality rates have increased faster than mortality rates for any other leading cause of cancer. “It’s important for clinicians to learn about the changing epidemiology of malignancies because this information directly impacts patient care,” says Jennifer C. Obel, MD.

Several treatment options are available for patients with early-stage HCC, including resection, transplantation, and liver-directed therapies like chemoembolization (in well-selected patients with localized HCC). However, many patients who are diagnosed with HCC have advanced disease and are only candidates for palliative therapies. “Most HCC is thought to be associated with either chronic hepatitis C virus (HCV) or hepatitis B virus (HBV) infection,” Dr. Obel says. “In the U.S., more than 3 million people are chronically infected with HCV. Chronic infection with HBV is less common overall, but more common among certain ethnic groups.” HCC typically develops in patients with underlying cirrhosis. Commonly reported risk factors for cirrhosis include alcohol-induced liver disease, HCV and HBV infection, obesity, and type 2 diabetes.

Assessing Incidence & Survival

In the March 2009 issue of the Journal of Clinical Oncology, researchers at the National Cancer Institute examined trends in HCC from 1975 to 2005. The report found that the incidence of HCC tripled in the United States during this time period. Between 2000 and 2005, liver cancer rates increased significantly among African-American, Hispanic, and Caucasian men between the ages of 50 and 59 (Table 1). The researchers suggest that increases in this age group may be partially due to an epidemic of hepatitis C infection that occurred in the 1960s when they were young adults.

“Despite the rising incidence of HCC,” says Dr. Obel, “the 2- to 4-year survival rates doubled from 1975 to 2005 [Table 2]. This improvement may be attributed to the fact that more patients were diagnosed with early-stage HCC when the disease can be cured by surgery. When detected early, there are significantly more treatment options for HCC.” Dr. Obel added that this finding is significant because it is important not only to diagnose cancer, but these early diagnoses must improve outcomes to have the desired effect.

Dr. Obel notes that aggressive treatments appear to be improving long-term survival in HCC patients. “Transplantation and resection have improved in recent years,” she says. “Also, the advent of targeted chemotherapies holds promise for patients with regional and advanced-stage HCC.”

Surveillance Important for High-Risk Patients

According to Dr. Obel, it is important for clinicians to monitor patients at increased risk of HCC. “Around the U.S.,” she says, “patients at increased risk for developing HCC are being entered into surveillance programs in which they are followed by serum alpha-fetoprotein testing, abdominal ultrasound, and diagnostic imaging approximately every 6 months. Active surveillance has the potential to diagnose patients when the disease is asymptomatic. An early diagnosis is our most formidable way to cure liver cancer.”

In addition to surveillance, Dr. Obel says that aggressive treatments appear to be improving long-term survival in HCC patients with localized-stage tumors. “In addition to improvements in transplantation and resection, there have also been advances in the development of targeted HCC therapies. These agents hold some promise for further improvements in prognoses, especially among patients with regional and distant-stage HCC. The key is to ensure that clinicians assess the risk of HCC in those patients with underlying conditions that place them at increased risk. After that, patients can subsequently be enrolled into screening programs for HCC, similar to how patients with substantial risk factors for colon cancer are screened more aggressively with colonoscopy.”

Coordinated Efforts Required

Dr. Obel notes that prevention efforts need to be coordinated. “The Journal of Clinical Oncology study indicated that despite better HCC survival rates, improvements are still needed,” she says. “The 1-year cause-specific survival rate remained lower than 50%. Primary HCC prevention measures should include hepatitis B vaccination programs, screening of the blood supply for hepatitis viruses, and campaigns to discourage IV drug abuse. Other prevention measures should focus on detecting asymptomatic HCC. This can be accomplished by periodically screening high-risk patients and then conducting follow-up tests when suspicious lesions are detected. The data reported in the study give us hope that greater awareness of liver cancer and its risk factors may help lessen the burden of HCC.”