Rates of Liver Cancer are Rising, but Survival is Increasing

March 4, 2009 — The incidence of hepatocellular carcinoma (HCC) in the United States tripled between 1975 and 2005, with much of the increase between 2000 and 2005 occurring among men 50 to 59 years. But even though incidence and mortality have increased substantially, HCC survival rates are improving, according to a report published online February 17 in the Journal of Clinical Oncology.

Researchers found that the 1-year survival rate nearly doubled between 1992 and 2005, increasing from 25% to 47%. Improvement in survival rates coincided with increasing numbers of patients being diagnosed with localized stage HCC (28% in 1992 to 1993 and 44% in 2003 to 2004).

"Early screening for patients with hepatitis C, a leading risk factor for liver cancer, has directly contributed to increasing survival rates for patients living with liver cancer," said Jennifer Obel, MD, an official of the American Society of Clinical Oncology and an attending physician at NorthShore University HealthSystem, in Illinois. Dr. Obel was not involved in the study.

"When detected early, there are significantly more treatment options for liver cancer — in most cases, the earlier it is caught, the better the prognosis," she said in a statement. "This study points to the need to identify even more at-risk individuals through early-screening programs to improve prognosis with potentially curative therapy."

Infection with chronic hepatitis C virus (HCV) or hepatitis B virus (HBV) is associated with the development of HCC. More than 3 million people are chronically infected with HCV in the United States, but chronic infection with HBV, a major global risk factor for HCC, is less common. However, among certain ethnic groups residing in the United States, the researchers note, HBV is a more common risk factor than HCV.

Etiology Complex, More Data Needed
The etiology of HCC is complex, and most likely involves interactions between multiple risk factors. In this study, Sean F. Altekruse, DVM, MPH, PhD, from the National Cancer Institute (NCI), in Bethesda, Maryland, and colleagues examined data on incidence trends, mortality rates, and survival rates from NCI's Surveillance Epidemiology and End Results (SEER) cancer registries. Their goals were to monitor changes in the burden of HCC and to define the populations most at risk, in an effort to help control the disease.

"SEER registries don't tell us the etiology, so we can only speculate on what may be driving the rates," Dr. Altekruse said in an interview. "Liver cancer typically begins with a hepatic insult, such as chronic inflammation, and then may progress to cirrhosis, and ultimately HCC."

Cancer occurs at a very late stage in the process, and Dr. Altekruse emphasized that not all patients infected with hepatitis will go through these stages, although infection with HBV and/or HCV is associated with an increased risk. "It is believed that there was an epidemic of hepatitis C that began in the 1960s and extended into the 1970s," he said. "It was projected that we would be seeing an increase in rates of HCC because of that."

But hepatitis infection is not the only risk factor. "We do need studies to better understand the proportion of HCC that is attributable to hepatitis, and we need to better understand the etiology of hepatitis C," Dr. Altekruse told Medscape Oncology. "We also need to study other possible contributing factors, such as alcohol consumption, obesity, diabetes mellitus, and iron-storage diseases."

Incidence Rising Among All Ethnic/Racial Groups
Their results showed that between 1975 and 2005 the rate of HCC tripled, from 1.6 cases to 4.9 cases per 100,000 people, and incidence was also approximately 3 times higher among men than among women during this time. Between 1992 and 2005, overall incidence rates of HCC increased, with an annual change of 4.3%.

The incidence of HCC increased among all ethnic/racial groups, with the greatest annual percentage change (APC) increase seen in the American Indian/Alaska native group (5.0%). This was followed increases in black (APC, 4.9%), white (APC, 4.6%), and Hispanic (APC, 4.0%) groups. Even though the Asian/Pacific Islander group had the highest incidence of HCC, it experienced a smaller APC (1%) than other groups. During the 5-year period from 2000 to 2005, the researchers observed marked increases in incidence rates among Hispanic, black, and white middle-aged men.

During the 1992 to 2005 time period, patterns of HCC mortality were similar to those of incidence. The overall age-adjusted mortality rates rose, with an APC of 1.6%, and mortality was highest among the Asian/Pacific Islander group, followed by Hispanic, black, American Indian/Alaska native, and white groups. Although the APC significantly increased among the Hispanic (1.7%), white (1.7%), and black (1.3%) groups, it declined for the Asian/Pacific Islander group (–0.9%). Mortality rates remained stable among the American Indian/Alaska native group.

Survival Improving in Patients With Localized Disease
An additional finding was that overall survival rates increased, and 2- to 4-year cause-specific survival rates doubled. The 1-year survival rates jumped from 65% in 1992 to 1993 to 83% in 2003 to 2004 among patients with localized HCC who reported undergoing treatment. Increases in survival were also observed among patients with localized HCC who underwent surgery, from 81% in 1992 to 1993 to 91% in 2003 to 2004.

"The most dramatic improvement in survival has been among people with localized disease," said Dr. Altekruse. "If screening can detect patients with early-stage HCC, it can truly have an important impact on the burden of liver cancer, which is projected to increase over the next 20 years."

The study was supported by the Division of Cancer Control and Population Sciences, Surveillance Research Program, National Cancer Institute, National Institutes of Health. The researchers have disclosed no relevant financial relationships.

J Clin Oncol. Published online before print February 17, 2009.